Unit Database Research Articles

The Association between Rheumatic Diseases and the Risk of Polycystic Ovary Syndrome: A Two-Sample Mendelian Randomization Analysis

Aims/Background The association between rheumatic immune diseases and polycystic ovary syndrome (PCOS) remains elusive. The purpose of this study was to investigate the causal relationship between rheumatic immune diseases and the risk of PCOS through a two-sample Mendelian randomization (MR) analysis. Methods In the assessment of exposure variables, we chose systemic lupus erythematosus (SLE), polymyositis (PM), and rheumatoid arthritis (RA) as representative rheumatic immune diseases, while PCOS was designated as the outcome of interest. All data utilized in this investigation were obtained from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) database. A two-sample MR analysis was conducted using summary statistics for both the exposure and outcome variables, which were gathered from the genome-wide association study (GWAS) datasets. Single nucleotide polymorphisms (SNPs) significantly associated with rheumatic diseases were selected as instrumental variables (IVs) to estimate the causal effects on PCOS. The final results were analyzed using five MR analysis methods, namely MR-Egger, inverse variance weighted (IVW), weighted median (WM), simple mode, and weighted mode. Causal estimation of MR was primarily obtained using the IVW method. Sensitivity analyses were also conducted to evaluate pleiotropy and heterogeneity. Results In this two-sample MR analysis, a total of 1,000,246 participants were included. Among them, there were 647 cases of SLE, 44 cases of PM, 5539 cases of RA, and 797 cases of PCOS. The IVW approach indicated a causal relationship between RA and an increased risk of PCOS (odds ratio [OR] = 1.069, 95% confidence interval [CI] = 1.007–1.134, p = 0.041). The MR-Egger intercept and Cochran’s Q test (p > 0.005) further verified the stability of the MR results. However, no significant correlation was observed between the other two rheumatic immune diseases (PM and SLE) and the risk of developing PCOS (both p > 0.05). Conclusion This study suggests a potential causal association between RA and PCOS, while SLE and PM do not exhibit a causal association with PCOS, enhancing our comprehension of the etiological factors of PCOS and shedding light on prevention strategies for the disease. Additional research is required to elucidate the underlying biological mechanisms by which RA contributes to the progression of PCOS.

Genetically Predicted Body Composition and Risk of Surgical Site Infection: A Mendelian Randomization Study.

Objective: This study employed uni-variable and multi-variable Mendelian randomization (MVMR) analyses, utilizing publicly available genome-wide association study (GWAS) data, to assess the causal relationship between body composition measures such as body mass index (BMI), waist circumference (WC), and the occurrence of surgical site infection (SSI). Patients and Methods: GWAS summary statistical data were obtained for BMI, WC, and SSI from the MRC Integrated Epidemiology Unit (MRC-IEU) database, inverse variance weighted (IVW) method was used as the main analysis, and supplement sensitivity analysis (including heterogeneity test, pleiotropy analysis, leave-one-out analysis, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO)) was used to check the robustness of the results. Results: The MR analysis showed that the increase in BMI and WC predicted by genes had a substantial causal effect on the incidence of SSI (IVW: odds ratio [OR] = 1.003, 95% confidence interval [CI] = 1.002-1.004, p < 0.001; IVW: OR = 1.003, 95% CI = 1.002-1.005, p < 0.001), respectively, and the MVMR analysis showed that after jointly incorporating smoking and alcohol parameters, the impact of BMI and WC on SSI remained substantial (OR = 1.003, 95% CI = 1.002-1.004, p < 0.001; OR = 1.004, 95% CI = 1.002-1.005, p < 0.001). Conclusion: We further support the causal relationship between increased body composition including BMI and WC and the occurrence of SSI, highlighting the importance of SSI prevention in patients with obesity. Further research is required to mitigate the occurrence of surgical incisions in patients with obesity in the future.

Abstract 4117414: Risk Factors Associated with Cardiac Hospital Admissions in Cancer Patients Treated with Immune Checkpoint Inhibitors

Background: Immune checkpoint inhibitors (ICIs) are highly effective anti-cancer treatments for several cancers. However, treatment with ICIs is associated with metabolic perturbations, accelerated atherosclerosis, and increased risks of adverse cardiovascular events. In this study, we aimed to determine risk factors associated with cardiac hospital admissions in patients treated with ICIs for their cancer. Methods: Retrospective data was collected for all patients treated with ICIs between 1 January 2010 and 1 January 2020 through the Hunter New England Local Health District (HNELHD), Australia. Patient medical history and demographics were collected through electronic medical records. Outcome data was obtained from the HNELHD Institutional Cardiac and Stroke Outcomes Unit database. Cardiac admission was defined as cardiac disease based on hospital administration ICD-10 codes. Binary logistic regression was used for multivariate analysis and performed through SPSS version 28. Results: A total of 1,080 patients were included in the final analysis. Mean age of patients was 66.9 ± 11.7 years, with the majority male sex ( n =685; 63.4%). Primary cancer diagnosis of patients treated with ICIs included melanoma ( n =417; 38.7%), and cancer of the lung ( n =327; 30.3%). Nivolumab monotherapy was the most used first-line ICI treatment ( n =475; 44.0%) followed by pembrolizumab monotherapy ( n =428; 39.6%). A total of 266 (24.6%) patients had at least one cardiac hospital admission. On univariate analysis, pre-existing cardiovascular disease (CVD) ( p &lt;0.001), diabetes mellitus ( p &lt;0.001), chronic kidney disease ( p &lt;0.001), and prior CVD medications ( p &lt;0.001) were associated with cardiac hospitalisation. On multivariate analysis, prior history of heart failure ( p &lt;0.001), hypertension ( p =0.003), ischaemia, and peripheral vascular disease ( p =0.049) were independently associated with an increased risk of cardiac hospital admission. Conclusions: In cancer patients treated with ICIs, pre-existing CVD risk factors increases the risk of cardiac-associated hospitalisations. Adequate CVD risk modification and monitoring during treatment with ICIs may be necessary to reduce cardiac hospitalisations.

Causal relationship between leukocyte telomere length and two cardiomyopathies based on a bidirectional Mendelian randomization approach.

This study aims to employ the Mendelian randomization (MR) approach to investigate the relationship between leukocyte telomere length (TL) and 2 prevalent forms of cardiomyopathies. Using R software (4.3.1) for MR study, independent genetic variants associated with leukocyte TL were extracted from the Integrative Epidemiology Unit database, while cardiomyopathies data were pooled from FinnGen and European Bioinformatics Institute databases. Analytical methodologies included inverse-variance weighting, MR-Egger regression, and weighted median methods. Further analyses involved MR-Egger intercept and MR-PRESSO for handling horizontal pleiotropy and Cochran Q test for study heterogeneity. Our forward Mendelian randomization study indicates a positive correlation between longer leukocyte TL and the risk of 2 forms of cardiomyopathies: the longer the leukocyte telomere, the higher is the risk of cardiomyopathies. Specifically, for hypertrophic obstructive cardiomyopathy the OR is 2.23 (95% CI: 1.19-4.14, P = .01), for hypertrophic cardiomyopathy the OR is 1.80 (95% CI: 1.14-2.85, P = .01), and for dilated cardiomyopathy the OR is 1.32 (95% CI: 1.01-1.71, P = .04). In contrast, our reverse Mendelian randomization showed that cardiomyopathies were not directly associated with TL, and the inverse-variance-weighted test was not statistically significant for any of the 3 (P > .05). The reliability tests for the forward Mendelian randomization, including both MR-Egger intercept and MR-PRESSO tests, show no evidence of horizontal pleiotropy, and Cochran Q test indicates no heterogeneity. The "leave-one-out" sensitivity analysis revealed no outlier genes. The reliability tests for the reverse Mendelian randomization, including both MR-Egger intercept and MR-PRESSO tests, also indicate no genetic pleiotropy. Despite the heterogeneity shown in our study between hypertrophic cardiomyopathy and leukocyte TL, the sensitivity analysis did not identify any anomalies. Our Mendelian randomization study suggests that longer leukocyte TL is associated with an increased risk of hypertrophic obstructive cardiomyopathy, hypertrophic cardiomyopathy, and dilated cardiomyopathy. However, the onset of these 2 kinds of disease does not directly lead to changes in leukocyte TL.

Genetic Testing and Analysis in Breast Cancer Patients in Greece.

Introduction Genetic testing for inherited breast cancer predisposing pathogenic variants (PVs) inform treatment choices and guide clinical management strategies in breast cancer patients. Methods The study enrolled 146 patients, sourced from the Breast Unit database of the First Department of Obstetrics and Gynecology at the University of Athens, AlexandraHospital. Blood samples were collected for genetic testing, utilizing a detailed 94-cancer gene panel. The results were then descriptively correlated with the clinicopathological data of the patients. Results In this study, 17 PVs were identified across several genes,BRCA1 (10), BRCA2 (3), CHEK2 (3) and TP53 (1), while 4 variants of unknown clinical significance (VUSs) were found in BRCA2 (1), CHEK2 (1), BRIP1 (1), MSH2 (1). This corresponds to a prevalence rate of 11.6% (17/146). Cascade testing was conducted for 7 of the 17 positive families, resulting in 11 individuals being tested, of whom 3 tested positive.  Conclusions Our study findings on the selected Greek population align with current literature. Genetic testing following National Comprehensive Cancer Network (NCCN) guidelines offers valuable insights for patients and their families. This information enhances counseling and identifying germline PVs could refine treatment strategies, potentially improving prognostic outcomes.

A validated NICU database: recounting 50 years of clinical growth, quality improvement and research.

The importance of a Neonatal Intensive Care Unit (NICU) database lies in its critical role in improving the quality of care for very preterm neonates and other high-risk newborns. These databases contain extensive information regarding maternal exposures, pregnancy complications, and neonatal care. They support quality improvement (QI) initiatives, facilitate clinical research, and track health outcomes in order to identify best practices and improve clinical guidelines. The Parkland Memorial Hospital NICU database was originally part of the Maternal and Neonatal Data Acquisition, Transmission and Evaluation project funded by the Robert Wood Johnson Foundation to assess perinatal-neonatal care in Dallas County Texas, 1977-1982. Clinical data points were defined, transcribed and validated in 1977; revalidation has occurred multiple times. Data are prospectively extracted from health records of high-risk neonates among >11,000 births annually. The database contains clinical information on >50,000 neonates, including all initially admitted to the NICU regardless of gestational age or birthweight and since 10/03/2011, all neonates admitted for observation and transferred to the term newborn nursery. The database has provided the basis for QI studies and research designed to assess and improve neonatal care. We discuss the history, evolution, administration, impact on neonatal outcomes, and future directions of our database. IMPACT: A single neonatal intensive care unit (NICU) database was designed for prospective data collection, validated and maintained for 46yrs. This database has supported quality improvement assessment, original clinical research, education and administrative requirements and impacted clinical neonatal care.

An Evaluation of Patient Profiles and Outcomes in an Off-Site Rehabilitation Unit in 2023 Compared to 2019

Abstract Background Our off-site inpatient rehabilitation unit accepts patients from many different referral centres. Demographic shifts have occurred in the last 4 years with the Covid-19 pandemic resulting in several practice changes and frailty admissions increasing at our primary referral centre by 11%. We compared the number of patients, their demographics and dependency in 2023 in comparison with 2019 and hypothesised a longer length of stay could be explained by increased dependency as defined by Barthel score on admission. Methods Data regarding patients’ age, admission and discharge dates, referral source and discharge destination were extracted from the rehabilitation unit's database. Weekly MDT records were examined to identify the patients’ presentation and dependency level. Presentations were categorised as stroke, hip fracture, other fracture, acute medical and surgical presentations, and elective surgical procedures. Results Discharges decreased to 89 in 2023 compared to 125 in 2019. Mean length of stay increased to 35.1 from 29.5. Mean age reduced from 85 to 83. Mean Barthel on admission was unchanged at 10. 21 Patients were admitted following elective orthopaedic surgery in 2019 compared to 2 in 2023 with a mean length of stay of 16 days. Length of stay for stroke patients increased from 33 to 50. Excluding both led to a length of stay of 32 in both years. Conclusion The reduction of bed days could be explained by increased frequency of outbreaks and more robust isolation strategies reducing total bed availability. A significant reduction in patients admitted following elective orthopaedic surgery impacted the average length of stay as did an increase in length of stay for stroke patients. Patient dependency defined by Barthel score was not increased and did not explain the increased length of stay. A more comprehensive score such as the Rehabilitation Complexity Score may be more predictive of complexity and thus length of stay.

Stroke after heart valve surgery: a single center institution report

IntroductionStroke is a potentially debilitating complication of heart valve replacement surgery, with rates ranging from 1 to 10%. Despite advancements in surgical techniques, the incidence of postoperative stroke remains a significant concern, impacting patient outcomes and healthcare resources. This study aims to investigate the incidence, risk factors, and outcomes of in-hospital adverse neurologic events, particularly stroke, following valve replacement. The analysis focuses on identifying patient characteristics and procedural factors associated with increased stroke risk.MethodsThis retrospective study involves a review of 417 consecutive patients who underwent SVR between January 2004 and December 2022. The study cohort was extracted from a prospectively recorded cardiac intensive care unit database. Preoperative and perioperative data were collected, and subjects with specific exclusion criteria were omitted from the analysis. The analysis includes demographic information, preoperative risk factors, and perioperative variables.ResultsThe study identified a 4.3% incidence of postoperative stroke among SVR patients. Risk factors associated with increased stroke susceptibility included prolonged cardiopulmonary bypass time, aortic cross-clamp duration exceeding 90 min, prior stroke history, diabetes mellitus, and mitral valve annulus calcification. Patients undergoing combined procedures, such as aortic valve replacement with mitral valve replacement or coronary artery bypass grafting with AVR and MVR, (OR = 10.74, CI:2.65–43.44, p-value = < 0.001) and (OR = 11.66, CI:1.02–132.70, p-value = 0.048) respectively, exhibited elevated risks. Internal carotid artery stenosis (< 75%) and requiring prolonged inotropic support were also associated with increased stroke risk(OR = 3.04, CI:1.13–8.12, P-value = 0.026). The occurrence of stroke correlated with extended intensive care unit stay (OR = 1.12, CI: 1.04–1.20, P-value = 0.002) and heightened in-hospital mortality.ConclusionIn conclusion, our study identifies key risk factors and underscores the importance of proactive measures to reduce postoperative stroke incidence in surgical valve replacement patients.

FP7.20 - Peri-orbital burns: A 5-Year Review of the Epidemiological Characteristics and Outcomes at a Regional Burns Centre in the UK 2019 – 2023

Abstract Background Burn injuries are a major cause of global morbidity. Despite being infrequent, peri-orbital and ocular burns can have significant implications on a patient’s vision and overall quality of life. In Northern Ireland, the current epidemiological landscape of peri-orbital burns is not clear. This study aimed at assessing the incidence of peri-orbital and ocular burns and the management outcomes of patients admitted at the regional burns unit in Northern Ireland 2019-2023. Methods Patients admitted to the regional burns unit in Northern Ireland between January 2019 and September 2023 with periorbital burns were identified from the burns unit electronic records, the burns unit database and hospital image database. Results Over 5 years, 100 patients with facial burns were treated, including 60 patients with eyelid burns. 71% were males and 29% were females with a mean age of 47 years. The mean burn size was 14% total body surface area. The burn depth varied; 55% superficial partial thickness, 22% mixed, 17% full thickness and 6% deep dermal. Majority of burns were flame burns 64%. In total, 7 patients sustained corneal burns, one patient responded to steroids, one underwent amniotic membrane grafting, one lost complete vision in both eyes, one had physical debridement and topical antimicrobials and three patients required periorbital reconstruction to maintain eye closure. Conclusion 60% of Facial burns were associated with eyelid burns, the majority of which were caused by flame burns and were managed conservatively with wound cleaning, physical debridement, and application of topical antimicrobials. Despite being rare, complete loss of vision was associated with mortality among our patients.

411. IMPACT OF FEEDING ADJUNCTS AND RADIOLOGICAL SARCOPENIA ON OUTCOMES IN NEO-ADJUVANT TREATED OESOPHAGEAL CANCER PATIENTS

Abstract Introduction Nutritional management plays a pivotal role in the care of patients with oesophageal cancer, particularly for those presenting with complete dysphagia, which poses a significant management challenge. Establishing adequate nutrition is not only a prerequisite for initiating neo-adjuvant treatment in cases of potentially curable disease but is also crucial for patient survival and quality of life. Additionally, emerging evidence suggests that sarcopenia, significantly predicts post-operative complications following oesophageal surgery. Our study aims to evaluate the impact of feeding adjuncts during neo-adjuvant treatment on outcomes, including post-operative complications, and to investigate the prevalence and implications of radiological sarcopenia in these patients. Methods Data from the Northern Oesophago-Gastric Cancer Unit database was used to identify patients diagnosed with oesophageal cancer and discussed at the multidisciplinary team (MDT) meetings from 2017 to 2021. The focus was on those deemed curable with planned neo-adjuvant treatment followed by surgery. Through MDT notes review, patients were identified that required feeding adjuncts prior to surgery. Demographics, tumour characteristics, treatment modalities, hospital stay length, complication rates, and survival outcomes were collected. Radiological sarcopenia was evaluated at initial staging and re-staging computed tomography (CT) scans. Results 353 patients were included; 15 required pre-operative feeding adjuncts. This subgroup was predominantly male (73%), with a higher proportion having squamous cell carcinoma (SCC) (34% V 17%). Progression to surgery was lower in the adjunct group (73% V 87%, p=0.11). Post-operative hospital stay and one-year survival rates were comparable between groups. The adjunct group had a higher incidence of severe post-operative complications (50% Vs 28% Clavien-Dindo grade ≥3, p=0.08). Radiological sarcopenia was higher in the adjunct group (70% Vs 52%, p=0.18), with no cases of sarcopenia reversal after re-staging in the adjunct group, versus 9% in the non-adjunct group. Conclusion These findings highlight an association between complete dysphagia in patients with potentially curable oesophageal cancer and increased rates of post-operative complications and pre-operative radiological sarcopenia. Notably, these patients are more likely to be female and have SCC. The data underscore the critical need for diligent monitoring and nutritional support for patients requiring feeding adjuncts in the neo-adjuvant phase, emphasizing the broader implications of nutritional status on surgical outcomes and overall patient care in oesophageal cancer management.

A Dedicated Menopausal After Cancer Clinic May Improve Adherence to Endocrine Therapy For Breast Cancer: A Population Based Study

PurposeTo examine utilization of a dedicated menopause symptoms after cancer clinic (MSAC) and to determine whether women referred to the MSAC for management of severe hot flush symptoms are more likely to adhere to endocrine therapy compare to those with severe symptoms not referred to MSAC. Patients and methodsBreast cancer patients prescribed endocrine therapy with a diagnosis of estrogen-receptor positive breast cancer between January 2003 and December 2011 were identified from the Royal Perth Hospital Breast Unit database. Details of breast cancer pathology, endocrine therapy, endocrine therapy related side effects, referral to MSAC and patient reported adherence to endocrine therapy for up to 4 years were ascertained from the database and medical records systems. For those with severe vasomotor symptoms, total duration of endocrine therapy was compared between women referred to MSAC and those who were not referred to MSAC. ResultsAbout 1275 women were identified from the database, with the cohort followed up until Dec 2016. Of these women, 120 (9.4%) were referred to MSAC and 1155 (90.1%) received usual care. In total, 147 reported severe vasomotor symptoms of whom almost half (71) were referred to MSAC. Women with severe vasomotor symptoms managed by MSAC were less likely to discontinue endocrine therapy (15.5%) compared with those managed with usual care (26.3%). However, this difference was not statistically significant (chi-square test statistic = 2.584, 1df, P = .1). ConclusionManagement of severe vasomotor symptoms at a dedicated menopause clinic may increase adherence to endocrine therapy for breast cancer.

MycoAI: Fast and accurate taxonomic classification for fungal ITS sequences.

Efficient and accurate classification of DNA barcode data is crucial for large-scale fungal biodiversity studies. However, existing methods are either computationally expensive or lack accuracy. Previous research has demonstrated the potential of deep learning in this domain, successfully training neural networks for biological sequence classification. We introduce the MycoAI Python package, featuring various deep learning models such as BERT and CNN tailored for fungal Internal Transcribed Spacer (ITS) sequences. We explore different neural architecture designs and encoding methods to identify optimal models. By employing a multi-head output architecture and multi-level hierarchical label smoothing, MycoAI effectively generalizes across the taxonomic hierarchy. Using over 5 million labelled sequences from the UNITE database, we develop two models: MycoAI-BERT and MycoAI-CNN. While we emphasize the necessity of verifying classification results by AI models due to insufficient reference data, MycoAI still exhibits substantial potential. When benchmarked against existing classifiers such as DNABarcoder and RDP on two independent test sets with labels present in the training dataset, MycoAI models demonstrate high accuracy at the genus and higher taxonomic levels, with MycoAI-CNN being the fastest and most accurate. In terms of efficiency, MycoAI models can classify over 300,000 sequences within 5 min. We publicly release the MycoAI models, enabling mycologists to classify their ITS barcode data efficiently. Additionally, MycoAI serves as a platform for developing further deep learning-based classification methods. The source code for MycoAI is available under the MIT Licence at https://github.com/MycoAI/MycoAI.

Bacteria, Fungi, and Scalp Psoriasis: Understanding the Role of the Microbiome in Disease Severity.

Background: Psoriasis is a chronic skin condition affected by genetic and environmental factors. Changes in the skin microbiome may affect the immune system and skin barrier functions, thereby contributing to the development and progression of psoriasis. The scalp, which is a common site for psoriasis, is often resistant to therapy. Although several studies have investigated the scalp microbiome, analyses focusing on both bacteria and fungi remain scarce. Methods: We examined the scalp microbiomes of 11 patients with psoriasis complicated with scalp lesions and categorized them according to their Psoriasis Area Severity Index (PASI) scores. The bacterial and fungal data were analyzed using QIIME2 pipeline version 2021.04 and the UNITE database version 8.3, respectively. Results: The Shannon indices for mild (2 patients), moderate (4 patients), and severe (5 patients) groups were 0.97, 1.38, and 1.88, respectively. A significant correlation was observed between increased mycobiome diversity and disease severity (p = 4.07 × 10-5, Spearman's correlation: 0.9269). Compared with the mild and moderate groups, the severe group exhibited a higher abundance of Malassezia globosa. Pseudomonas and Staphylococcus were, respectively, more prevalent in the moderate and severe groups than in the mild group. Conclusions: This study highlights the potential role of increased fungal diversity and specific microbial compositions in the severity of scalp psoriasis, suggesting a possible avenue for targeted therapeutic interventions.

Reducing Hospital Length of Stay and Hepatic Artery Thrombosis Rates for Children Receiving a Liver Transplant: A Single-Center Experience From 2000 to 2021.

Pediatric liver transplantation is a very resource-intensive therapy. This study aimed to identify the changes made between two epochs of management and analyze their influence on length of stay (LOS). Data from a single center were obtained from the liver transplant and Pediatric Intensive Care Unit (PICU) databases for 336 transplants (282 children) performed between 2000 and 2021. Transplants were analyzed in two epochs, before and after July 2012, representing a change in postoperative anticoagulation management. Differences in graft recipient demographics and perioperative management factors were compared between epochs. Multivariate regression was performed to identify the complications that correlated most strongly with hospital LOS. There was a difference in hospital LOS between Epoch 1 (Median = 31.7 days) and Epoch 2 (Median = 26.3 days) (p < 0.001), but not in PICU LOS (E1 Median = 7.3 days, E2 Median = 7.4 days; p = 0.792). Epoch 2 saw increased use of split grafts (60.6% of total), decreased pediatric end-stage liver disease (PELD) score at transplant (Average = 16.7; p < 0.001), decreased invasive ventilation time (Average = 4.48 days; p < 0.001), and decreased hepatic artery thrombosis (HAT) rates (E1 = 14.4%, E2 = 4.3%; p < 0.001) without an associated increase in bleeding rates. Hospital LOS has reduced in Epoch 2 due to refinements in intraoperative and postoperative management. There is increased emphasis on early extubation and increased use of noninvasive ventilatory techniques in Epoch 2. Split grafts have effectively expanded our graft donor pool and reduced transplant waitlist times.

Autoimmune diseases and COPD risk: A Mendelian randomization study

BackgroundStudies in epidemiology have indicated a link between chronic obstructive pulmonary disease (COPD) and various autoimmune conditions.This study aimed to investigate the potential causal link between nine autoimmune diseases with a genetic basis and COPD using a two-sample Mendelian randomization (MR) analysis. MethodTo test the impact of susceptibility to immune-related outcomes on genetic prediction of COPD risk, we used pooled statistics from the largest genome-wide association study (GWAS) in Europe in a two-sample MR setting.Genetic data for type 1 diabetes, hypothyroidism, systemic lupus erythematosus, and primary biliary cirrhosis were obtained from the European Bioinformatics Institute (EBI), while data for multiple sclerosis and primary sclerosing cholangitis were extracted from the Integrative Epidemiology Unit (IEU) database. Additionally, genetic data for ulcerative colitis, rheumatoid arthritis, and celiac disease were also collected.These nine autoimmune diseases and the COPD cohort from the UK Biobank (1605 cases and 461,328 controls) were analyzed separately as exposure and outcome.Our primary method for the initial screening was inverse variance weighting (IVW).The MR-Egger regression test assessed multivariate validity, while the Cochran’s Q test examined heterogeneity.To ensure the reliability of the findings, a leave-one-out analysis was conducted. ResultIVW discovered proof of type 1 diabetes (OR = 1.0003; 95 % CI = 1.0000–1.0005; P = 0.046), hypothyroidism (OR = 1.0004; 95 % CI = 1.0001–1.0008; P = 0.0263), celiac disease (OR = 1.0002; 95 % CI = 1.0000–1.0004; P = 0.0168) and systemic lupus erythematosus (OR = 1.0002; 95 % CI = 1.0000–1.0004; P = 0.049) were significantly linked to the heightened risk of COPD with no signs of variation or pleiotropy.Even after accounting for potential confounding factors like smoking, the correlation remained robust.Additionally, our research found that the IVW method did not indicate any causal link between COPD and multiple sclerosis, ulcerative colitis, rheumatoid arthritis, primary biliary cirrhosis, or primary sclerosing cholangitis (all P >0.05). ConclusionThis research discovered that individuals with type 1 diabetes, hypothyroidism, celiac disease, and systemic lupus erythematosus have a higher likelihood of developing COPD.Additionally, this research revealed no connection between COPD and multiple sclerosis, ulcerative colitis, rheumatoid arthritis, primary biliary cirrhosis, or primary sclerosing cholangitis.

Contrast-Enhanced Mammography in Local Staging of Screen-Detected Breast Cancer.

BreastScreen Australia, the population mammographic screening program for breast cancer, uses two-view digital screening mammography ± ultrasound followed by percutaneous biopsy to detect breast cancer. Secondary breast imaging for further local staging, not performed at BreastScreen, may identify additional clinically significant breast lesions. Staging options include further mammography, bilateral ultrasound, and/or contrast-based imaging (CBI) [magnetic resonance imaging (MRI) or contrast-enhanced mammography (CEM)]. CBI for local staging of screen-detected cancer was introduced at an academic hospital breast service in Melbourne, VIC, Australia. We report findings for otherwise occult disease and resulting treatment changes. Patients staged using CEM between November 2018 and April 2022 were identified from hospital records. Data were extracted from radiology, pathology, and breast unit databases. CEM-detected abnormalities were documented as true positive (TP) for invasive cancer or ductal carcinoma in situ (DCIS), or otherwise false positive (FP). The impact on surgical decisions was assessed. Of 202 patients aged 44-84 years, 60 (30%) had 74 additional findings [34 (46%) TP, 40 (54%) FP]. These were malignant in 29/202 (14%) patients (79% invasive cancers, 21% DCIS). CEM resulted in surgical changes in 43/202 (21%) patients: wider resection (24/43), conversion to mastectomy (6/43), contralateral breast surgery (6/43), additional ipsilateral excision (5/43), and bracketing (2/43). Additional findings were more common for patients with larger index lesions and for invasive cancer, but there was no significant variation by age, breast density, or index lesion grade. CEM for local staging of screen-detected breast cancers identified occult malignancy in 14% of patients. CEM improves local staging and may facilitate appropriate management of screen-detected breast cancers.

Universal screening for Lynch syndrome in endometrial cancer diagnoses in Auckland, New Zealand: The initial experience.

Universal mismatch repair immunohistochemistry (MMR IHC) tumour testing in endometrial cancer (EC) for Lynch syndrome (LS) was introduced in Auckland, New Zealand, in January 2017. Identifying patients with LS allows them and their families to access risk reduction strategies. Universal MMR IHC testing aids in the molecular classification of EC and has prognostic and therapeutic implications. We aimed to determine the incidence of LS in women with EC in Auckland, New Zealand, following the introduction of MMR testing and the impact of universal screening on local genetic services. This is a retrospective clinicopathological evaluation of women with a new EC diagnosis referred to the Auckland Gynaecological Oncology Unit from 1/1/17 to 31/12/18. Patient data were extracted from the Gynaecological Oncology Unit database and electronic records, and analysed using descriptive statistics. During the study period, 409 patients were diagnosed with EC, with an over-representation of Pacific Islanders (32.5%). Of these, 82.6% underwent MMR IHC testing, 20% were MMR-deficient (MMRd), and 71% had somatic hypermethylation. The Pacific Islander population had a 64% (odds ratio 0.36, P = 0.005) reduction in the odds of having MMRd tumours compared with Europeans. Of the patients who underwent MMR IHC testing, 5.5% were referred to a genetic clinic for germline testing. LS was confirmed in eight patients (2.3%). LS was diagnosed in 2.3% of patients. There was an over-representation of Pacific Islanders in the EC group but not among those diagnosed with LS.

Soil fungal communities associated with chili pepper respond to mineral and organic fertilization and application of the biocontrol fungus Trichoderma harzianum

Soil fungi are diverse and common in crop systems with important ecological function such as saprotrophs, symbionts, and pathogens, all of which are key components for soil fertility and health. Agricultural practices including tillage, crop rotation, fertilization and pest management with pesticides and microbial biocontrol agents are known to affect the abundance and composition of soil fungi, but these factors are seldom integrated and studied in combination. The objective of this study was to examine the influence of mineral and organic (compost) fertilization, and soil inoculation with the biocontrol fungus Trichoderma harzianum individually and in combination on the resident soil fungal communities and plant performance in a greenhouse pot experiment with chili pepper grown in a disease-infested agricultural soil. Soil fungal communities were studied using Illumina MiSeq sequencing and taxonomic assignment using the UNITE database in terms of amplicon sequence variants (ASV). Main results showed that the combination of compost and T. harzianum inoculation completely controlled chili pepper wilt, which coincided with alterations in soil fungal diversity. The root pathogen Fusarium equiseti was the most abundant fungus (in relative terms) in all treatments and the ASV Trichoderma sp. was only found in the treatments in which T. harzianum had been applied. Soil application with T. harzianum at sowing also reduced chili pepper damping-off in non-sterile disease-infested soil, which coincided with a reduction of the relative abundance of F. equiseti. However, several other known Fusarium spp. pathogens were present in the natural disease infested agricultural soil and could also have been involved in the chili pepper wilt observed. In conclusion, our results show promising biocontrol traits of T. harzianum against chili pepper damping off and wilt most likely caused by Fusarium spp. The observed alterations in soil fungal diversity with T. harzianum and compost were probably involved in the reduction of chili pepper wilt but needs to be further studied.

A BRILLIANT-BRCA study: residual breast tissue after mastectomy and reconstruction

IntroductionDifferent types of mastectomies leave different amounts of residual breast tissue. The significance of the residual breast volume (RBV) is not clear. Therefore, we developed an MRI tool that allows to easily assess the RBV. In this study we evaluated factors associated with RBV after skin or nipple sparing mastectomy (SSM/NSM) in breast cancer BRCA pathogenic variant (PV) carriers who underwent both therapeutic and risk reducing SSM/NSM and its relation to breast cancer outcomes using an innovative MRI-based tool.MethodsData of breast cancer BRCA PV who were treated between 2006 and 2020 were retrieved from of the oncogenetics unit databases. Only patients who underwent SSM/NSM and had a postoperative breast MRI available for analysis were included. Data collected included demographics, clinicopathological features, and outcomes. The MRI tool was developed by a breast cancer imaging laboratory. A logistic regression test and 95% confidence interval (CI) were used to assess the associated risk of increased RBV. A forward stepwise linear regression was used to correlate tumour-patient specific factors and RBV, and a Kaplan–Meier curve to show the probability of locoregional relapse.ResultsA total of 84 patients undergoing 89 mastectomies were included. At a median follow-up of 98 months, 5 local, 2 regional, and 4 distant recurrences were observed. RBV was not significantly related with breast cancer outcomes (p value = NS). A higher body mass index (BMI) was associated with a higher RBV (p < 0.0001). A larger number of involved axillary nodes was associated with a smaller RBV (p = 0.025). The RBV on the risk-reducing mastectomy side was significantly higher compared to the breast cancer side (p value = 0.007). Local recurrences occurred in the vicinity of the primary tumour.

The role of gut microbiota in prostate cancer progression: A Mendelian randomization study of immune mediation.

The potential relationship between the gut microbiota and prostate cancer, possibly influenced by immune cells, remains unclear. This study employed the mediation Mendelian randomization (MR) technique to investigate the causal link between the gut microbiota, immune cells, and prostate cancer. Data on immune cell activity were sourced from Valeria Orrù's research, whereas the genome-wide association study outcome dataset was obtained from the Integrative Epidemiology Unit database. The bidirectional MR analysis utilized 5 different methods: inverse variance weighted (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode. In addition, the mediating effect of immune cells on the gut microbiota and prostate cancer was explored using mediation analysis. Eighty-three single nucleotide polymorphisms associated with prostate cancer were screened as instrumental variables. In a positive MR analysis with gut microbiota as the exposure factor, IVW showed an association between 8 gut microbiota and prostate cancer. Additionally, 9 types of immune cells have been found to be associated with prostate cancer using methods such as IVW. MR analysis of the gut microbiota on immune cells (beta1) revealed a negative correlation between Bifidobacterium and CD39+ T regulatory cells (Tregs; odds ratio [OR] = 0.785, 95% confidence interval [CI] = 0.627-0.983, P = .03). Furthermore, MR analysis of immune cells in prostate cancer disease (beta2) showed that CD39+Tregs are a risk factor for prostate cancer (OR = 1.215, 95% CI = 1.027-1.354, P = .04). Moreover, MR analysis of gut microbiota in prostate cancer (total effect) indicated that Bifidobacterium is a protective factor for prostate cancer (OR = 0.905, 95% CI = 0.822-0.977, P = .04). The sensitivity analysis verified the robustness of the above results. Mediation analysis demonstrated that CD39+Tregs partially mediate the causal relationship between Bifidobacterium and prostate cancer. This study demonstrates that Bifidobacterium inhibits prostate cancer progression through CD39+Tregs as mediators, providing new ideas and approaches for the treatment and prevention of prostate cancer.