Cause Of Death Research Articles

The role of a digital twin in supporting criminal investigations - a case report about a possible abuse.

As part of a comprehensive analysis, this case report presents a possible case of child maltreatment that can serve as a basis for forensic and medical examiner investigations. This case concerns the death of an infant who was approximately two months old. During a routine examination by the pediatrician at the end of May 2021, the child was found to have a normal head circumference of 31 cm. No other abnormalities were noted. On June 19, 2021, the child died, and an autopsy revealed a head circumference of 44 cm and a subdural hematoma as the cause of death. Questions arose as to who might have abused the child and when. The only evidence was a low-quality cell phone video taken by the child's parents on June 13, 2021, six days before the child's death, in which the child could be seen lying on a pillow. It was necessary to determine whether the child in this video already had an unnatural head circumference. This study presents a novel workflow that demonstrates how to analyze and deal with low quality video to answer questions like the above. The workflow demonstrates the creation of 3D scenes from digital image and video material. These 3D scenes can be used for object measurement and to support forensic and medical investigations. In the present case, where only low quality smartphone images were available, the presented workflow was used to create a 3D scene of the child lying on the pillow. In this 3D scene, it was possible to determine the child's head circumference. These measurements support the findings of the medical examiner (dated June 24, 2021) and confirm the suspicion that possible child abuse had already taken place on June 13, 2021. The innovative approach makes it possible to identify evidence of possible abuse based on a specific point in time, in this case the child's private footage. It also demonstrates the potential of 3D scene reconstruction in complex forensic and medical scenarios.

Dual-Engineered Macrophage-Microbe Encapsulation for Metastasis Immunotherapy.

Lung metastases are the leading cause of death among cancer patients. The challenges of inefficient drug delivery, compounded by a robust immunosuppressive microenvironment, make effective treatment difficult. Here, an innovative dual-engineered macrophage-microbe encapsulation (Du-EMME) therapy is developed that integrates modified macrophages and engineered antitumor bacteria. These engineered macrophages, termed R-GEM cells, are designed to express RGD peptides on extracellular membranes, enhancing their tumor cell binding and intratumor enrichment. R-GEM cells are cocultured with attenuated Salmonella typhimurium VNP20009, producing macrophage-microbe encapsulation (R-GEM/VNP cells). The intracellular bacteria maintain bioactivity for more than 24h, and the bacteria released from R-GEM/VNP cells within the tumor continue to exert bacteria-mediated antitumor effects. This is further supported by macrophage-based chemotaxis and camouflage, which enhance the intratumoral enrichment and biocompatibility of the bacteria. Additionally, R-GEM cells loaded with IFNγ-secreting strains (VNP-IFNγ) form R-GEM/VNP-IFNγ cells. Treatment with these cells effectively halts lung metastatic tumor progression in three mouse models (breast cancer, melanoma, and colorectal cancer). R-GEM/VNP-IFNγ cells vigorously activate the tumor microenvironment, suppressing tumor-promoting M2-type macrophages, MDSCs, and Tregs, and enhancing tumor-antagonizing M1-type macrophages, mature DCs, and Teffs. Du-EMME therapy offers a promising strategy for targeted and enhanced antitumor immunity in treating cancer metastases.

All-cause and cause-specific mortality risk and loss in life expectancy associated with incident type 2 diabetes onset age and duration.

Evidence on type 2 diabetes onset age and duration on mortality risk has been limited by short follow-up, inadequate control for confounding, missing repeated measurements, and inability to cover the full range of onset age, duration, and major causes of death. Moreover, scarce data dissect how type 2 diabetes onset age and duration shape life expectancy. We evaluate prospectively these topics based on 270,075 eligible participants in the Nurses' Health Studies and Health Professionals Follow-up Study, leveraging repeated measurements throughout up to 40 years of follow-up. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In fully adjusted analyses, incident early onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all-causes (HR, 95% CI was 3.16, 2.64-3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27-10.1), respiratory disease (3.43, 1.38-8.51), neurodegenerative disease (5.13, 2.09-12.6), and kidney disease (8.55, 1.98-36.9). The relative risk elevations declined dramatically with each higher decade of age at diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Longer disease duration was associated with generally higher relative and absolute risk of mortality. Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all-cause and cause-specific mortality and greater loss in life expectancy.

Experiences and challenges of acute coronary syndrome patients in care provision: a qualitative systematic review

BackgroundCoronary artery disease including acute coronary syndrome (ACS) constitutes the most common cause of death in people with cardiovascular disease. Prompt diagnosis and early initiation of treatment significantly impact on patient outcomes. Positive patient experience with their initial care is linked to positive clinical outcomes.ObjectiveThis qualitative review aimed to investigate patients’ experience of care provision and the challenges faced by them during their different stages of care following an ACS.MethodsSearches of four databases - MEDLINE, Embase, CINAHL and PsychINFO - were conducted from inception until July 13, 2022, and were limited to English-language publications. Assessment of methodological quality of studies was performed using the Jonna Briggs Institute (JBI) qualitative assessment and review instrument. Data were extracted using the standardised data extraction tool from JBI. Data synthesis following the JBI approach of meta-aggregation was performed. The level of confidence for each synthesised finding was established based on ConQual.ResultsOverall, from 578 records, 10 studies were included with 39 findings extracted from the included studies. The main synthesised findings were the need to provide tailored information and appropriate management at different stages of care, and that timely management and trust in health care workers are associated with greater patient satisfaction and more positive experiences.ConclusionPatients with an ACS experience many challenges during different stages of their care. Clinicians should be aware of the challenges they face and provide tailored information to patients that is appropriate for their different stages of management in order to best optimise patient experience and improve patient outcomes.

Classification of Suicide Attempt Risk Using Environmental and Lifestyle Factors in 3 Large Youth Cohorts.

Suicide is the third-leading cause of death among US adolescents. Environmental and lifestyle factors influence suicidal behavior and can inform risk classification, yet quantifying and incorporating them in risk assessment presents a significant challenge for reproducibility and clinical translation. To quantify the aggregate contribution of environmental and lifestyle factors to youth suicide attempt risk classification. This was a cohort study in 3 youth samples: 2 national longitudinal cohorts from the US and the UK and 1 clinical cohort from a tertiary pediatric US hospital. An exposome-wide association study (ExWAS) approach was used to identify risk and protective factors and compute aggregate exposomic scores. Logistic regression models were applied to test associations and model fit of exposomic scores with suicide attempts in independent data. Youth from the Adolescent Brain Cognitive Development (ABCD) study, the UK Millennium Cohort Study (MCS), and the Children's Hospital of Philadelphia emergency department (CHOP-ED) were included in the study. A single-weighted exposomic score that sums significant risk and protective environmental/lifestyle factors. Self-reported suicide attempt. A total of 40 364 youth were included in this analysis: 11 564 from the ABCD study (3 waves of assessment; mean [SD] age, 12.0 [0.7] years; 6034 male [52.2%]; 344 attempted suicide [3.0%]; 1154 environmental/lifestyle factors were included in the ABCD study), 9000 from the MCS cohort (mean [SD] age, 17.2 [0.3] years; 4593 female [51.0%]; 661 attempted suicide [7.3%]; 2864 environmental/lifestyle factors were included in the MCS cohort), and 19 800 from the CHOP-ED cohort (mean [SD] age, 15.3 [1.5] years; 12 937 female [65.3%]; 2051 attempted suicide [10.4%]; 36 environmental/lifestyle factors were included in the CHOP-ED cohort). In the ABCD discovery subsample, ExWAS identified 99 risk and protective exposures significantly associated with suicide attempt. A single weighted exposomic score that sums significant risk and protective exposures was associated with suicide attempt in an independent ABCD testing subsample (odds ratio [OR], 2.2; 95% CI, 2.0-2.6; P < .001) and explained 17.6% of the variance (based on regression pseudo-R2) in suicide attempt over and above that explained by age, sex, race, and ethnicity (2.8%) and by family history of suicide (6.3%). Findings were consistent in the MCS and CHOP-ED cohorts (explaining 22.6% and 19.3% of the variance in suicide attempt, respectively) despite clinical, demographic, and exposure differences. In all cohorts, compared with youth at the median quintile of the exposomic score, youth at the top fifth quintile were substantially more likely to have made a suicide attempt (OR, 4.3; 95% CI, 2.6-7.2 in the ABCD study; OR, 3.8; 95% CI, 2.7-5.3 in the MCS cohort; OR, 5.8; 95% CI, 4.7-7.1 in the CHOP-ED cohort). Results suggest that exposomic scores of suicide attempt provided a generalizable method for risk classification that can be applied in diverse samples from clinical or population settings.

Prolonged hospitalization signature and early antibiotic effects on the nasopharyngeal resistome in preterm infants

Respiratory pathogens, commonly colonizing nasopharynx, are among the leading causes of death due to antimicrobial resistance. Yet, antibiotic resistance determinants within nasopharyngeal microbial communities remain poorly understood. In this prospective cohort study, we investigate the nasopharynx resistome development in preterm infants, assess early antibiotic impact on its trajectory, and explore its association with clinical covariates using shotgun metagenomics. Our findings reveal widespread nasopharyngeal carriage of antibiotic resistance genes (ARGs) with resistomes undergoing transient changes, including increased ARG diversity, abundance, and composition alterations due to early antibiotic exposure. ARGs associated with the critical nosocomial pathogen Serratia marcescens persist up to 8–10 months of age, representing a long-lasting hospitalization signature. The nasopharyngeal resistome strongly correlates with microbiome composition, with inter-individual differences and postnatal age explaining most of the variation. Our report on the collateral effects of antibiotics and prolonged hospitalization underscores the urgency of further studies focused on this relatively unexplored reservoir of pathogens and ARGs.

Looking at the future of the medical certification of cause of death (MCCD) in England and Wales.

Internationally, the quality of death certification is poor although there are multiple efforts underway to improve the process. In England, a new medical certification system has been proposed to improve the quality of data. We surveyed general practitioners (n = 95) across the West Yorkshire area of England to appraise their views regarding whether further possible changes to the death certification system could promote their quality.

Monoclonal Antibodies Engineered with Fc Region Mutations to Extend Protection against Fentanyl Toxicity.

Fentanyl and other synthetic opioids are the leading cause of drug-related deaths in the United States. mAbs that selectively target fentanyl and fentanyl analogues offer a promising strategy for treating both opioid-related overdoses and opioid use disorders. To increase the duration of efficacy of a candidate mAb against fentanyl, we selected three sets of mutations in the Fc region of an IgG1 anti-fentanyl mAb (HY6-F9DF215, HY6-F9DHS, HY6-F9YTE) to increase binding to the neonatal Fc receptor (FcRn). The mAb mutants were compared against unmodified (wild-type [WT], HY6-F9WT) anti-fentanyl mAb for fentanyl binding, thermal stability, and FcRn affinity invitro, and for efficacy against fentanyl and mAb half-life invivo in mice. Biolayer interferometry showed a >10-fold increase in the affinity for recombinant FcRn of the three mutant mAbs compared with HY6-F9WT. During an acute fentanyl challenge in mice, all FcRn-mutated mAbs provided equal protection against fentanyl-induced effects, and all mAbs reduced brain fentanyl levels compared with the saline group. Serum persistence of the mutant mAbs was tested in Tg276 transgenic mice expressing human FcRn. After administration of 40 mg/kg HY6-F9WT, HY6-F9DF215, HY6-F9DHS, and HY6-F9YTE, the mAbs showed half-lives of 6.3, 26.4, 14.7, and 6.9 d, respectively. These data suggest that modification of mAbs against fentanyl to bind to FcRn with higher affinity can increase their half-life relative to WT mAbs while maintaining efficacy against the toxic effects of fentanyl, further supporting their potential role as a therapeutic treatment option for opioid use disorder and overdose.

Metabolic dysfunction-associated steatotic liver disease has become the most common cause of hepatocellular carcinoma in Sweden: A nationwide cohort study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally, and can lead to hepatocellular carcinoma (HCC), a leading cause of cancer-related death. We aimed to determine the extent to which MASLD is an increasing cause of HCC in Sweden and to determine clinical characteristics associated with underlying MASLD. Using the Swedish quality registry for liver cancer (SweLiv), we identified all adults with a diagnosis of HCC in Sweden between 2012 and 2018. Baseline data were retrieved from SweLiv and other nationwide registers. Totally, 3494 patients with HCC were identified. Of them, 757 patients (22%) had MASLD-HCC. The proportion with MASLD-HCC increased from 19% in 2012 to 25% in 2018 (ptrend = 0.012), and MASLD was since 2017 the leading cause of HCC, surpassing hepatitis C. MASLD was the fastest growing cause of HCC with a 33% increment during the study period. Compared to other patients with HCC, those with MASLD-HCC were older (75 vs. 67 years, p < .001), less commonly had cirrhosis (61% vs. 82%, p < .001), had larger tumours (median 5.5 vs. 4.3 cm, p < .001), and more often extrahepatic metastasis (22% vs. 16%, p < .001). Patients with HCC caused by MASLD or by other causes were equally likely to be diagnosed in an early stage (Barcelona Clinic Liver Cancer 0-A, 27% vs. 30%, p = .129). MASLD is now the leading cause of HCC in Sweden.

Unrecognised COVID-19 deaths in central Europe: The importance of cause-of-death certification for the COVID-19 burden assessment.

In Central Europe, the increase in mortality during the COVID-19 pandemic exceeded the number of deaths registered due to coronavirus disease. Excess deaths reported to causes other than COVID-19 may have been due to unrecognised coronavirus disease, the interruptions in care in the overwhelmed health care facilities, or socioeconomic effects of the pandemic and lockdowns. Death certificates provide exhaustive medical information, allowing us to assess the extent of unrecognised COVID-19 deaths. Data from 187,300 death certificates with a COVID-19 mention from Austria, Bavaria (Germany), Czechia, Lithuania and Poland, 2020-2021, was used. The two step analysis uses Cause of Death Association Indicators (CDAIs) and Contributing CDAIs to identify and measure the statistical strength of associations between COVID-19 and all other medical mentions. 15,700 deaths were reported with COVID-19 only as a contributing condition (comorbidity). In three cases out of four, a typical, statistically significant coronavirus complication or pre-existing condition was registered as the underlying causes of death. In Austria, Bavaria, Czechia and Lithuania the scale of COVID-19 mortality would have been up to 18-27% higher had COVID-19 been coded as the underlying cause of death. Unrecognised coronavirus deaths were equivalent to the entire surplus of excess mortality beyond registered COVID-19 deaths in Austria and the Czech Republic, and its large proportion (25-31%) in Lithuania and Bavaria. Death certificates with typical coronavirus complications or comorbidities as the underlying causes of death and contributing COVID-19 mentions were plausibly unrecognized coronavirus deaths.

Comparison of fatalities due to COVID-19 and other nonexternal causes during the first five pandemic waves : Results from multiple cause of death statistics in Bavaria.

Older age is arisk factor for afatal course of SARS-CoV‑2 infection, possibly due to comorbidities whose exact role in this context, however, is not yet well understood. In this paper, the characteristics and comorbidities of persons who had died of COVID-19 in Bavaria by July 2022 are shown and compared with the characteristics of other fatalities during the pandemic. Based on data from multiple cause of death statistics, odds ratios for dying from COVID-19 (compared to dying from other nonexternal causes of death) were calculated by using logistic regression models, stratified by age, sex, and pandemic waves. In Bavaria, atotal of 24,479 persons (6.5% of all deaths) officially died from COVID-19 between March 2020 and July 2022. In addition to increasing age and male sex, preexisting diseases and comorbidities such as obesity, degenerative diseases of the nervous system, dementia, renal insufficiency, chronic lower respiratory diseases, and diabetes mellitus were significantly associated with COVID-19-related deaths. Dementia was mainly associated with increased COVID-19 mortality during the first and second waves, while obesity was strongly associated during the fourth wave. The frequency of specific comorbidities in COVID-19 deaths varied over the course of the pandemic. This suggests that wave-specific results also need to be interpreted against the background of circulating virus variants, changing immunisation levels, and nonpharmaceutical interventions in place at the time.

Etiology-Specific Effects of Impaired Functional Status on Liver Transplant Outcomes.

Pre-liver transplant (LT) functional status is an important determinant of prognosis post LT. There is insufficient data on how functional status affects outcomes of transplant recipients based on the specific etiology of liver disease. We stratified LT recipients by etiology of liver disease to evaluate the effects of functional status on post-LT prognosis in each subgroup. 2005-2019 United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) was used to select patients with liver transplant. A total of 14,290 patients were included in the analysis. These patients were stratified by functional status according to Karnofsky Performance Scale (KPS) score: no assistance, some assistance, or total assistance. They were then further divided into six diagnosis categories: metabolic dysfunction-associated steatotic liver disease (MASLD), hereditary disorders, hepatitis C, hepatitis B, autoimmune disease (AID), and alcoholic liver disease (ALD). Primary endpoints included all-cause mortality and graft failure, while secondary endpoints included organ-specific causes of death. Those under the age of 18 and those with non-whole liver or prior liver transplantation were excluded. Patients with MASLD requiring some assistance (aHR: 1.57, 95% CI 1.03-2.39, p = 0.04) and those requiring total assistance (aHR: 2.32, 95% CI 1.48-3.64, p < 0.001) had higher incidences of graft failure compared to those requiring no assistance. Those with MASLD requiring total assistance had a higher all-cause mortality rate than those needing no assistance (aHR: 1.62, 95% CI 1.38-1.89, p < 0.001). Patients with hereditary causes of liver disease showed a lower incidence of all-cause mortality in recipients needing some assistance compared with those needing no assistance (aHR: 0.52, 95% CI 0.34-0.80, p = 0.003). LT recipients with hepatitis C, AID, and ALD all showed higher incidences of all-cause mortality in the total assistance cohort when compared to the no assistance cohort. For the secondary endpoints of specific cause of death, transplant recipients with MASLD needing total assistance had higher rates of death due to general cardiac causes, graft rejection, general infectious causes, sepsis, general renal causes, and general respiratory causes. Patients with MASLD cirrhosis demonstrated the worst overall outcomes, suggesting that this population may be particularly vulnerable. Poor functional status in patients with end-stage liver disease from hepatitis B or hereditary disease was not associated with a significantly increased rate of adverse outcomes, suggesting that the KPS score may not be broadly applicable to all patients awaiting LT.

Post-Ischemic Stroke Cardiovascular Risk Prevention and Management

Cardiac death is the second most common cause of death among patients with acute ischemic stroke (IS), following neurological death resulting directly from acute IS. Risk prediction models and screening tools including electrocardiograms can assess the risk of adverse cardiovascular events after IS. Prolonged heart rate monitoring and early anticoagulation therapy benefit patients with a higher risk of adverse events, especially stroke patients with atrial fibrillation. IS and cardiovascular diseases have similar risk factors which, if optimally managed, may reduce the incidence of recurrent stroke and other major cardiovascular adverse events. Comprehensive risk management emphasizes a healthy lifestyle and medication therapy, especially lipid-lowering, glucose-lowering, and blood pressure-lowering drugs. Although antiplatelet and anticoagulation therapy are preferred to prevent cardiovascular events after IS, a balance between preventing recurrent stroke and secondary bleeding should be maintained. Optimization of early rehabilitation care comprises continuous care across environments thus improving the prognosis of stroke survivors.

Breast Cancer Detection and Localizing the Mass Area Using Deep Learning

Breast cancer presents a substantial health obstacle since it is the most widespread invasive cancer and the second most common cause of death in women. Prompt identification is essential for effective intervention, rendering breast cancer screening a critical component of healthcare. Although mammography is frequently employed for screening purposes, the manual diagnosis performed by pathologists can be laborious and susceptible to mistakes. Regrettably, the majority of research prioritizes mass classification over mass localization, resulting in an uneven distribution of attention. In response to this problem, we suggest a groundbreaking approach that seeks to identify and pinpoint cancers in breast mammography pictures. This will allow medical experts to identify tumors more quickly and with greater precision. This paper presents a complex deep convolutional neural network design that incorporates advanced deep learning techniques such as U-Net and YOLO. The objective is to enable automatic detection and localization of breast lesions in mammography pictures. To assess the effectiveness of our model, we carried out a thorough review that included a range of performance criteria. We specifically evaluated the accuracy, precision, recall, F1-score, ROC curve, and R-squared error using the publicly available MIAS dataset. Our model performed exceptionally well, with an accuracy rate of 93.0% and an AUC (area under the curve) of 98.6% for the detection job. Moreover, for the localization task, our model achieved a remarkably high R-squared value of 97%. These findings highlight that deep learning can boost the efficiency and accuracy of diagnosing breast cancer. The automation of breast lesion detection and classification offered by our proposed method bears substantial benefits. By alleviating the workload burden on pathologists, it facilitates expedited and accurate breast cancer screening processes. As a result, the proposed approach holds promise for improving healthcare outcomes and bolstering the overall effectiveness of breast cancer detection and diagnosis.

The association of breast cancer patients survival and prior menopausal hormone therapy in women with type 2 diabetes

We investigated the association of prediagnostic use of menopausal hormone therapy (MHT) with breast cancer survival among women with type 2 diabetes (T2D). The study cohort was identified from a Finnish nationwide diabetes database, and consisted of women with T2D, who were diagnosed with breast cancer between 2000 and 2011 (n = 3189). The patients were classified according to their previous MHT use: systemic MHT, local MHT, and no history of any MHT. The cumulative mortality from breast cancer, cardiovascular diseases, and other causes in three MHT groups was described by the Aalen-Johansen estimator. The cause-specific mortality rates were analyzed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of MHT. The breast cancer mortality appeared to be lower among systemic MHT users (HR 0.49, 95% Cl 0.36–0.67) compared with non-users of MHT. The mortality from cardiovascular diseases and from other causes of death was found to be lower among systemic MHT users, (HR 0.49, 95% Cl 0.32–0.74), and (HR 0.51, 95% Cl 0.35–0.76), respectively. In conclusion, prediagnostic systemic MHT use is associated with reduced breast cancer, cardiovascular, and other causes of mortality in women with T2D.

The pros and cons of lung cancer screening.

Several trials have shown that low-dose computed tomography-based lung cancer screening (LCS) allows a substantial reduction in lung cancer-related mortality, carrying the potential for other clinical benefits. There are, however, some uncertainties to be clarified and several aspects to be implemented to optimize advantages and minimize the potential harms of LCS. This review summarizes current evidence on LCS, discussing some of the well-established and potential benefits, including lung cancer (LC)-related mortality reduction and opportunity for smoking cessation interventions, as well as the disadvantages of LCS, such as overdiagnosis and overtreatment. CLINICAL RELEVANCE STATEMENT: Different perspectives are provided on LCS based on the updated literature. KEY POINTS: Lung cancer is a leading cancer-related cause of death and screening should reduce associated mortality. This review summarizes current evidence related to LCS. Several aspects need to be implemented to optimize benefits and minimize potential drawbacks of LCS.

Cohort profile: The Obesity and Disease Development Sweden (ODDS) study, a pooled cohort.

The Obesity and Disease Development Sweden (ODDS) study was designed to create a large cohort to study body mass index (BMI), waist circumference (WC) and changes in weight and WC, in relation to morbidity and mortality. ODDS includes 4 295 859 individuals, 2 165 048 men and 2 130 811 women, in Swedish cohorts and national registers with information on weight assessed once (2 555 098 individuals) or more (1 740 761 individuals), in total constituting 7 733 901 weight assessments at the age of 17-103 years in 1963-2020 (recalled weight as of 1911). Information on WC is available in 152 089 men and 212 658 women, out of whom 108 795 have repeated information on WC (in total 512 273 assessments). Information on morbidity and mortality was retrieved from national registers, with follow-up until the end of 2019-2021, varying between the registers. Among all weight assessments (of which 85% are objectively measured), the median year, age and BMI (IQR) is 1985 (1977-1994) in men and 2001 (1991-2010) in women, age 19 (18-40) years in men and 30 (26-36) years in women and BMI 22.9 (20.9-25.4) kg/m2 in men and 23.2 (21.2-26.1) kg/m2 in women. Normal weight (BMI 18.5-24.9 kg/m2) is present in 67% of assessments in men and 64% in women and obesity (BMI≥30 kg/m2) in 5% of assessments in men and 10% in women. The median (IQR) follow-up time from the first objectively measured or self-reported current weight assessment until emigration, death or end of follow-up is 31.4 (21.8-40.8) years in men and 19.6 (9.3-29.0) years in women. During follow-up, 283 244 men and 123 457 women died. The large sample size and long follow-up of the ODDS Study will provide robust results on anthropometric measures in relation to risk of common diseases and causes of deaths, and novel findings in subgroups and rarer outcomes.

A systematic review of reported outcomes in randomized controlled trials targeting early interventions in moderate-to-severe traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Randomized controlled trials (RCTs) are the cornerstone to evaluate the efficacy of an intervention. In order to assess the methodology of clinical research, we performed a systematic review which evaluated the different outcomes used in RCTs targeting the early phase of moderate to severe adult TBI from 1983 to October 31, 2023. We extracted each outcome and organized them according to the COMET and OMERACT framework (core area, broad domains, target domains and finally outcomes). 190 RCTs were included, including 52,010 participants. 557 outcomes were reported and classified between the following core areas: pathophysiological manifestations (169 RCTs (88.9%)), life impact (117 RCTs (61.6%)), death (94 RCTs (49.5%)), resource use (72 RCTs (37.9%)) and adverse events (41 RCTs (21.6%)). We identified 29 broad domains and 89 target domains. Among target domains, physical functioning (111 (58.4%)), mortality (94 (49.5%)), intra-cranial pressure target domain (68 (35.8%)), hemodynamics (53 (27.9%)) were the most frequent. Outcomes were mostly clinician-reported (177 (93.2%)) while patient-reported outcomes were rarely reported (11 (5.8%)). In our review, there was significant heterogeneity in the choice of endpoints in TBI clinical research. There is an urgent need for consensus and homogeneity in order to improve the quality of clinical research in this area.

State of the Art Modelling of the Breast Cancer Metastatic Microenvironment: Where Are We?

Metastatic spread of tumour cells to tissues and organs around the body is the most frequent cause of death from breast cancer. This has been modelled mainly using mouse models such as syngeneic mammary cancer or human in mouse xenograft models. These have limitations for modelling human disease progression and cannot easily be used for investigation of drug resistance and novel therapy screening. To complement these approaches, advances are being made in ex vivo and 3D in vitro models, which are becoming progressively better at reliably replicating the tumour microenvironment and will in the future facilitate drug development and screening. These approaches include microfluidics, organ-on-a-chip and use of advanced biomaterials. The relevant tissues to be modelled include those that are frequent and clinically important sites of metastasis such as bone, lung, brain, liver for invasive ductal carcinomas and a distinct set of common metastatic sites for lobular breast cancer. These sites all have challenges to model due to their unique cellular compositions, structure and complexity. The models, particularly in vivo, provide key information on the intricate interactions between cancer cells and the native tissue, and will guide us in producing specific therapies that are helpful in different context of metastasis.

The Prevalence of ST-Segment Elevation Myocardial Infarction in Patients Presenting in the Emergency Service of Galati Hospital from 2015 to 2019

Background and Objectives: The purpose of this study is to determine the prevalence of cardiovascular emergencies and the relationships between these emergencies and the personal medical histories of patients. Materials and Methods: This study is retrospective, observational, and longitudinal, spanning five years from 1 January 2015 to 31 December 2019. Descriptive elements were observed and recorded to conduct statistical analysis on the cardiovascular characteristics of 723 patients transported by air and treated at the Emergency County Hospital of Galati, Romania. Results: Cardiovascular disease is a complex condition that often originates in the heart and presents with a variety of symptoms. Deaths related to cardiovascular diseases outnumber cancer-related deaths in both men and women worldwide. The one-year mortality rate for patients admitted to the hospital with acute pulmonary edema can be as high as 40%. Coronary heart disease is the leading cause of death and disability in the Western world and globally. Conclusions: The highest prevalence of cardiovascular diseases was noted in 2016, particularly among elderly men, who appear to be more affected by these conditions, while liver disease was minimal. In our study, the most prevalent cardiovascular disease was ST-elevation myocardial infarction. Gender plays a role in the risk of cardiovascular emergencies, with men being at a higher risk of developing life-threatening conditions. Additionally, there is a linear increase in risk with age for developing these pathologies.