Smart hospital: achieving interoperability and raw data collection from medical devices in clinical routine.

Introduction: Today, modern technology is used to diagnose and treat cardiovascular disease. These medical devices provide exact measures and raw data such as imaging data or biosignals. So far, the Broad Integration of These Health Data into Hospital Information Technology Structures-Especially in Germany-is Lacking, and if data integration takes place, only non-Evaluable Findings are Usually Integrated into the Hospital Information Technology Structures. A Comprehensive Integration of raw Data and Structured Medical Information has not yet Been Established. The aim of this project was to design and implement an interoperable database (cardio-vascular-information-system, CVIS) for the automated integration of al medical device data (parameters and raw data) in cardio-vascular medicine. Methods: The CVIS serves as a data integration and preparation system at the interface between the various devices and the hospital IT infrastructure. In our project, we were able to establish a database with integration of proprietary device interfaces, which could be integrated into the electronic health record (EHR) with various HL7 and web interfaces. Results: In the period between 1.7.2020 and 30.6.2022, the data integrated into this database were evaluated. During this time, 114,858 patients were automatically included in the database and medical data of 50,295 of them were entered. For technical examinations, more than 4.5 million readings (an average of 28.5 per examination) and 684,696 image data and raw signals (28,935 ECG files, 655,761 structured reports, 91,113 x-ray objects, 559,648 ultrasound objects in 54 different examination types, 5,000 endoscopy objects) were integrated into the database. Over 10.2 million bidirectional HL7 messages (approximately 14,000/day) were successfully processed. 98,458 documents were transferred to the central document management system, 55,154 materials (average 7.77 per order) were recorded and stored in the database, 21,196 diagnoses and 50,353 services/OPS were recorded and transferred. On average, 3.3 examinations per patient were recorded; in addition, there are an average of 13 laboratory examinations. Discussion: Fully automated data integration from medical devices including the raw data is feasible and already creates a comprehensive database for multimodal modern analysis approaches in a short time. This is the basis for national and international projects by extracting research data using FHIR.

QRS fragmentation does not predict mortality in survivors of acute myocardial infarction.

BACKGROUND: Despite advances in coronary revascularization and in heart failure management, myocardial infarction survivors remain at substantially increased mortality risk. Precise risk assessment and risk-adapted follow-up care are crucial to improve their outcomes. Recently, the fragmented QRS complex, i.e. the presence of additional spikes within the QRS complexes on a 12-lead electrocardiogram, has been discussed as a potential non-invasive risk predictor in cardiac patients. HYPOTHESIS: The aim of this study was to evaluate the prognostic meaning of the fragmented QRS complex in myocardial infarction survivors. METHODS: 609 patients with narrow QRS complexes <120 ms were included in a prospective cohort study while hospitalized for myocardial infarction and followed for 5 years. RESULTS: The prevalence of the fragmented QRS complex in these patients amounted to 46.8% (285 patients). These patients had no increased hazard of all-cause death (HR 0.84, 95%-CI 0.45-1.57, p = 0.582) with a mortality rate of 6.0% compared to 7.1% in patients without QRS fragmentations. Furthermore, the risks of cardiac death (HR 1.28, 95%-CI 0.49-3.31, p = 0.613) and of non-cardiac death (HR 0.6, 95%-CI 0.26-1.43, p = 0.25) were not significantly different in patients with QRS fragmentations. However, patients with QRS fragmentations had increased serum creatine kinase concentrations (1438U/l vs. 1160U/l, p = 0.039) and reduced left ventricular ejection fractions (52% vs. 54%, p = 0.011). CONCLUSIONS: The hypothesis that QRS fragmentation might be a prognostic parameter in survivors of myocardial infarction was not confirmed. But those with QRS fragmentation had larger myocardial infarctions, as measured by creatine kinase and left ventricular ejection fraction.

DWT-CNNTRN: a Convolutional Transformer for ECG Classification with Discrete Wavelet Transform.

Cardiovascular diseases are the leading cause of death worldwide. The diagnoses of cardiovascular diseases are usually carried out by cardiologists utilizing Electrocardiograms (ECGs). To assist these physicians in making an accurate diagnosis, there is a growing need for reliable and automatic ECG classifiers.In this study, a new method is proposed to classify 12-lead ECG recordings. The proposed model is composed of four components: the CNN(Convolutional Neural Network) module, the transformer module, the global hybrid pooling layer, and a classification layer. To improve the classification performance, the model takes the discrete wavelet transform of ECG signals as the model inputs and utilizes a hybrid pooling layer to condense the most important features over each period.The proposed model is evaluated using the test set of the China Physiological Signal Challenge 2018 dataset with 12-lead ECGs. It performs with an average accuracy of 0.86 and an average F1-scores of 0.83. The scores are particularly good for the block conditions (LBBB, RBBB, I-AVB). The main advantage of the proposed model is that, it obtains good results with a significantly smaller number of parameters compared to other individual and ensemble models.Clinical relevance- This work establishes a new ECG classifier model with high performance and low model size. It can make automatic ECG analysis more accessible, efficient, and accurate, especially in remote or underserved areas.

[Venous access routes for cardiac implantable electronic devices]. / Venöse Zugangswege in der kardialen Devicetherapie.

Various venous access routes in the region of the clavicle are available for cardiac device treatment. After many years of choosing access via the subclavian vein, current data explicitly show that lateral approaches such as preparation of the cephalic vein or puncture of the axillary vein are clearly superior in terms of probe durability and risk of complications. This article describes the preparation and performance of the various access techniques and is intended to provide a practical guide for the work in cardiac pacemaker operations. This work continues a series of articles designed for advanced training in specialized rhythmology.

Telemedical monitoring in patients with inborn cardiac disease - experience of a tertiary care centre.

BACKGROUND: The number of cardiologically relevant genetic findings will continue to increase. This is due to the use of high-throughput sequencing techniques and the critical role of incidental findings in cardiac disease genes. Telemedicine can be a useful diagnostic tool to monitor the heart rhythm of patients with inborn cardiac diseases. METHODS: Patients were screened once they had been referred to our outpatient department for rare cardiac diseases between January 2020 and May 2022. Those patients who underwent genetic testing and were consequently diagnosed with a genetic disorder were included in this study. Their medical records were evaluated regarding implanted cardiac electronic devices and findings in the telemedical monitoring. RESULTS: 304 patients were seen in our outpatient department for rare cardiac diseases in the mentioned period. In 100 cases, genetic testing was performed. 10 patients (10%) with an identified inborn cardiac disease were monitored via telemedicine until the end of May 2022. 4 patients were monitored by implantable loop recorders (ILR), 4 patients were monitored by Implantable Cardioverter Defibrillators (ICD), and 2 patients received both devices. Clinical relevant arrhythmias making medical intervention necessary were identified in 4 cases. In two cases, data interpretation was hampered by sinus tachycardia caused by physical exercise. DISCUSSION: Telemonitoring of the heart rhythm by medical devices is beneficial for patients with monogenic heart diseases. Especially, when the indication for an ICD is not clear, implantation of a telemonitored ILR can be a suitable choice. However, rhythm analysis can be challenging in young patients who are physically active.

Prostaglandin E2 receptor EP1 expression in vulvar cancer.

PURPOSE: In recent years, incidence of vulvar cancer has been on the rise, whereas therapeutic options are still restricted. Therefore, new prognosticators and therapeutic targets are essential. Chronic inflammation plays an important role in carcinogenesis and COX-2, and its product prostaglandin E2 and its receptors EP1-4 are known to be important mediators in cancer initiation and progression. METHODS: EP1 expression in vulvar cancer specimens (n = 129) was investigated via immunohistochemistry and evaluated using the well-established immunoreactive score (IRS). Subsequently, the values were correlated with clinicopathological parameters. RESULTS: Our analysis did not reveal EP1 expression as a negative prognostic factor in overall and disease-free survival. However, in the subgroup of patients with lymph-node metastasis, overall survival was significantly shorter in tumors with high EP1 expression. Moreover, EP1 expression correlated positively with good differentiation of the tumor, but not with p16 status or COX-2 expression. CONCLUSIONS: This study shed first light on EP1 expression in vulvar carcinoma. EP1 expression correlated significantly with the grading of the tumor, suggesting that it influences cell differentiation. Further research on EP1 signaling may lead to a deeper understanding of the molecular mechanisms of carcinogenesis.

Heartbeat Classification by Random Forest With a Novel Context Feature: A Segment Label.

OBJECTIVE: Physicians use electrocardiograms (ECG) to diagnose cardiac abnormalities. Sometimes they need to take a deeper look at abnormal heartbeats to diagnose the patients more precisely. The objective of this research is to design a more accurate heartbeat classification algorithm to assist physicians in identifying specific types of the heartbeat. METHODS AND PROCEDURES: In this paper, we propose a novel feature called a segment label, to improve the performance of a heartbeat classifier. This feature, provided by a Convolutional Neural Network, encodes the information surrounding the particular heartbeat. The random forest classifier is trained based on this new feature and other traditional features to classify the heartbeats. RESULTS: We validate our method on the MIT-BIH Arrhythmia dataset following the inter-patient evaluation paradigm. The proposed method is competitive with other similar works. It achieves an accuracy of 0.96, and F1-scores for normal beats, ventricular ectopic beats, and Supra-Ventricular Ectopic Beats (SVEB) of 0.98, 0.93, and 0.74, respectively. The precision and sensitivity for SVEB are 0.76 and 0.78, which outperforms the state-of-the-art methods. CONCLUSION: This study demonstrates that the segment label can contribute to precisely classifying heartbeats, especially those that require rhythm information as context information (e.g. SVEB). Clinical impact: Using a medical devices embedding our algorithm could ease the physicians' processes of diagnosing cardiovascular diseases, especially for SVEB, in clinical implementation.

The Polyscore of autonomic parameters predicts mortality and identifies low-risk individuals among diabetic survivors of acute myocardial infarction.

Survivors of an acute myocardial infarction with diabetes mellitus retain an increased mortality risk. Reliable assessment of individual risk is required for effective and cost-efficient medical care in these patients. The Polyscore is a previously established risk predictor consisting of seven autonomic tests derived from electrocardiogram, blood pressure, and respiration. The Polyscore allows classification of survivors of myocardial infarction in groups at low, intermediate and high mortality risk. The aim of this study was to investigate the prognostic value of the Polyscore in diabetic survivors of acute myocardial infarction, which may be impaired by the presence of diabetic autonomic neuropathy. Survivors of an acute myocardial infarction were included in a prospective cohort study during hospitalisation due to the index event at two university hospitals in Munich, Germany. The Polyscore was determined from simultaneous non-invasive 30-min recordings of electrocardiogram, continuous arterial blood pressure, and respiration which were performed in all participants. Patients were followed for 5 years. The primary and secondary outcomes were all-cause mortality and cardiac mortality. 184 of 941 enrolled patients (19.6%) suffered from diabetes mellitus. 5-year-mortality was higher in diabetic patients (15.2%) compared to non-diabetic patients (5.8%). A multivariable Cox regression model confirmed the Polyscore as a strong predictor of mortality in diabetic post-MI patients (intermediate risk: HR 6.56, 95% CI 1.61-26.78, p = 0.004, mortality 22.8%; high risk: HR 18.76, 95% CI 4.35-80.98, p < 0.001, mortality 68.8%). There was no interaction between diabetes mellitus and the Polyscore regarding mortality prediction (p = 0.775). Interestingly, in contrast to the groups at intermediate and high risk (73 patients, 39.7%), the Polyscore identified a majority of diabetic patients (111, 60.3%) with a low mortality risk, comparable to that of low-risk non-diabetic patients (3.6% and 2.1%, respectively, p = 0.339). Consistent results were observed for cardiac mortality. This analysis shows that the Polyscore predicts all-cause and cardiac mortality in diabetic survivors of acute myocardial infarction. Within these patients it identifies a large population not affected by the excess mortality associated with diabetes in this setting. Thus, the Polyscore may facilitate risk-adapted follow-up strategies in diabetic survivors of myocardial infarction.

Remote monitoring of COVID-19 positive high-risk patients in domestic isolation: A feasibility study.

BACKGROUND: If a COVID-19 patient develops a so-called severe course, he or she must be taken to hospital as soon as possible. This proves difficult in domestic isolation, as patients are not continuously monitored. The aim of our study was to establish a telemonitoring system in this setting. METHODS: Oxygen saturation, respiratory rate, heart rate and temperature were measured every 15 minutes using an in-ear device. The data was transmitted to the Telecovid Centre via mobile network or internet and monitored 24/7 by a trained team. The data were supplemented by daily telephone calls. The patients´ individual risk was assessed using a modified National Early Warning Score. In case of a deterioration, a physician initiated the appropriate measures. Covid-19 Patients were included if they were older than 60 years or fulfilled at least one of the following conditions: pre-existing disease (cardiovascular, pulmonary, immunologic), obesity (BMI >35), diabetes mellitus, hypertension, active malignancy, or pregnancy. FINDINGS: 153 patients (median age 59 years, 77 female) were included. Patients were monitored for 9 days (median, IQR 6-13 days) with a daily monitoring time of 13.3 hours (median, IQR 9.4-17.0 hours). 20 patients were referred to the clinic by the Telecovid team. 3 of these required intensive care without invasive ventilation, 4 with invasive ventilation, 1 of the latter died. All patients agreed that the device was easy to use. About 90% of hospitalised patients indicated that they would have delayed hospitalisation further if they had not been part of the study. INTERPRETATION: Our study demonstrates the successful implementation of a remote monitoring system in a pandemic situation. All clinically necessary information was obtained and adequate measures were derived from it without delay.

Early Bronchoscopy Improves Extubation Rates after Out-of-Hospital Cardiac Arrest: A Retrospective Cohort Analysis.

BACKGROUND: Patients suffering from out-of-hospital cardiac arrest (OHCA) frequently receive a bronchoscopy after being admitted to the ICU. We investigated the optimal timing and the outcome in these patients. METHODS: All patients who suffered from OHCA and were treated in our ICU from January 2013 to December 2018 were retrospectively analyzed. The data were collected from the patients' medical files, and included duration of mechanical ventilation, antibiotics, microbiological test results and neurological outcome. The outcome was the effect of early bronchoscopy (≤48 h after administration) on the rate of intubated patients on day five and day seven. RESULTS: From January 2013 to December 2018, 190 patients were admitted with OHCA. Bronchoscopy was performed in 111 patients out of the 164 patients who survived the first day. Late bronchoscopy >48 h was associated with higher rates of intubation on day five (OR 4.94; 95% CI 1.2-36.72, 86.7% vs. 55.0%, p = 0.036) and day seven (OR 4.96; 95% CI 1.38-24.69; 80.0% vs. 43.3%, p = 0.019). CONCLUSION: This study shows that patients who suffered from OHCA might have a better outcome if they receive a bronchoscopy early after hospital admission. Our data suggests an association of early bronchoscopy with a shorter intubation period.

Immunogenomic Identification for Predicting the Prognosis of Cervical Cancer Patients.

Cervical cancer is primarily caused by the infection of high-risk human papillomavirus (hrHPV). Moreover, tumor immune microenvironment plays a significant role in the tumorigenesis of cervical cancer. Therefore, it is necessary to comprehensively identify predictive biomarkers from immunogenomics associated with cervical cancer prognosis. The Cancer Genome Atlas (TCGA) public database has stored abundant sequencing or microarray data, and clinical data, offering a feasible and reliable approach for this study. In the present study, gene profile and clinical data were downloaded from TCGA, and the Immunology Database and Analysis Portal (ImmPort) database. Wilcoxon-test was used to compare the difference in gene expression. Univariate analysis was adopted to identify immune-related genes (IRGs) and transcription factors (TFs) correlated with survival. A prognostic prediction model was established by multivariate cox analysis. The regulatory network was constructed and visualized by correlation analysis and Cytoscape, respectively. Gene functional enrichment analysis was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 204 differentially expressed IRGs were identified, and 22 of them were significantly associated with the survival of cervical cancer. These 22 IRGs were actively involved in the JAK-STAT pathway. A prognostic model based on 10 IRGs (APOD, TFRC, GRN, CSK, HDAC1, NFATC4, BMP6, IL17RD, IL3RA, and LEPR) performed moderately and steadily in squamous cell carcinoma (SCC) patients with FIGO stage I, regardless of the age and grade. Taken together, a risk score model consisting of 10 novel genes capable of predicting survival in SCC patients was identified. Moreover, the regulatory network of IRGs associated with survival (SIRGs) and their TFs provided potential molecular targets.

Nocturnal respiratory rate predicts ICD benefit: A prospective, controlled, multicentre cohort study.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death. ICD implantation decisions are currently based on reduced left ventricular ejection fraction (LVEF≤35%). However, in some patients, the non-arrhythmic death risk predominates thus diminishing ICD-therapy benefits. Based on previous observations, we tested the hypothesis that compared to the others, patients with nocturnal respiratory rate (NRR) ≥18 breaths per minute (brpm) benefit less from prophylactic ICD implantations. METHODS: This prospective cohort study was a pre-defined sub-study of EU-CERT-ICD trial conducted at 44 centers in 15 EU countries between May 12, 2014, and September 6, 2018. Patients with ischaemic or non-ischaemic cardiomyopathy were included if meeting primary prophylactic ICD implantation criteria. The primary endpoint was all-cause mortality. NRR was assessed blindly from pre-implantation 24-hour Holters. Multivariable models and propensity stratification evaluated the interaction between NRR and the ICD mortality effect. This study is registered with ClinicalTrials.gov (NCT0206419). FINDINGS: Of the 2,247 EU-CERT-ICD patients, this sub-study included 1,971 with complete records. In 1,363 patients (61.7 (12) years; 244 women) an ICD was implanted; 608 patients (63.2 (12) years; 108 women) were treated conservatively. During a median 2.5-year follow-up, 202 (14.8%) and 95 (15.6%) patients died in the ICD and control groups, respectively. NRR statistically significantly interacted with the ICD mortality effect (p = 0.0070). While the 1,316 patients with NRR<18 brpm showed a marked ICD benefit on mortality (adjusted HR 0.529 (95% CI 0.376-0.746); p = 0.0003), no treatment effect was demonstrated in 655 patients with NRR≥18 brpm (adjusted HR 0.981 (95% CI 0.669-1.438); p = 0.9202). INTERPRETATION: In the EU-CERT-ICD trial, patients with NRR≥18 brpm showed limited benefit from primary prophylactic ICD implantation. Those with NRR<18 brpm benefitted substantially. FUNDING: European Community's 7th Framework Programme FP7/2007-2013 (602299).

Polyscore of autonomic parameters for risk stratification of the elderly general population: the Polyscore study.

AIMS: Present society is constantly ageing and elderly frequently suffer from conditions that are difficult and/or costly to treat if detected late. Effective screening of the elderly is therefore needed so that those requiring detailed clinical work-up are identified early. We present a prospective validation of a screening strategy based on a Polyscore of seven predominantly autonomic, non-invasive risk markers. METHODS AND RESULTS: Within a population-based survey in Germany (INVADE study), participants aged ≥60 years were enrolled between August 2013 and February 2015. Seven prospectively defined Polyscore components were obtained during 30-min continuous recordings of electrocardiogram, blood pressure, and respiration. Out of 1956 subjects, 168 were excluded due to atrial fibrillation, implanted pacemaker, or unsuitable recordings. All-cause mortality over a median 4-year follow-up was prospectively defined as the primary endpoint. The Polyscore divided the investigated population (n = 1788, median age: 72 years, females: 58%) into three predefined groups with low (n = 1405, 78.6%), intermediate (n = 326, 18.2%), and high risk (n = 57, 3.2%). During the follow-up, 82 (4.6%) participants died. Mortality in the Polyscore-defined risk groups was 3.4%, 7.4%, and 17.5%, respectively (P < 0.0001). The Polyscore-based mortality prediction was independent of Framingham score, diabetes, chronic kidney disease, and major stroke and/or myocardial infarction history. It was particularly effective in those aged <75 years (n = 1145). CONCLUSION: The Polyscore-based mortality risk assessment from short-term non-invasive recordings is effective in the elderly general population, especially those aged 60-74 years. Implementation of a comprehensive Polyscore screening of this age group is proposed to advance preventive medical care.

Augmented Oscillations in QT Interval Duration Predict Mortality Post Myocardial Infarction Independent of Heart Rate.

OBJECTIVE: This study seeks to decompose QT variability (QTV) into physiological sources and assess their role for risk stratification in patients post myocardial infarction (MI). We hypothesize that the magnitude of QTV that cannot be explained by heart rate or respiration carries important prognostic information. BACKGROUND: Elevated beat-to-beat QTV is predictive of cardiac mortality, but the underlying mechanisms, and hence its interpretation, remain opaque. METHODS: We decomposed the QTV of 895 patients post MI into contributions by heart rate, respiration, and unexplained sources. RESULTS: Cox proportional hazard analysis demonstrates that augmented oscillations in QTV and their level of dissociation from heart rate are associated with a higher 5-year mortality rate (18.4% vs. 4.7%, p < 0.0001). In patients with left ventricular ejection fraction (LVEF) > 35%, a higher QTV risk score was associated with a significantly higher 5-year mortality rate (16% vs. 4%, p < 0.0001). In patients with a GRACE score ≥ 120, a higher QTV risk score was associated with a significantly higher 5-year mortality (25% vs. 11%, p < 0.001). CONCLUSION: Augmented oscillations in QTV and discordance from heart rate, possibly indicative of excessive sympathetic outflow to the ventricular myocardium, predict high risk in patients post MI independent from established risk markers. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT00196274.

Prediction of mortality benefit based on periodic repolarisation dynamics in patients undergoing prophylactic implantation of a defibrillator: a prospective, controlled, multicentre cohort study.

BACKGROUND: A small proportion of patients undergoing primary prophylactic implantation of implantable cardioverter defibrillators (ICDs) experiences malignant arrhythmias. We postulated that periodic repolarisation dynamics, a novel marker of sympathetic-activity-associated repolarisation instability, could be used to identify electrically vulnerable patients who would benefit from prophylactic implantation of ICDs by way of a reduction in mortality. METHODS: We did a prespecified substudy of EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD), a prospective, investigator-initiated, non-randomised, controlled cohort study done at 44 centres in 15 EU countries. Patients aged 18 years or older with ischaemic or non-ischaemic cardiomyopathy and reduced left ventricular ejection fraction (≤35%) were eligible for inclusion if they met guideline-based criteria for primary prophylactic implantation of ICDs. Periodic repolarisation dynamics from 24-h Holter recordings were assessed blindly in patients the day before ICD implantation or on the day of study enrolment in patients who were conservatively managed. The primary endpoint was all-cause mortality. Propensity scoring and multivariable models were used to assess the interaction between periodic repolarisation dynamics and the treatment effect of ICDs on mortality. FINDINGS: Between May 12, 2014, and Sept 7, 2018, 1371 patients were enrolled in our study. 968 of these patients underwent ICD implantation, and 403 were treated conservatively. During follow-up (median 2·7 years [IQR 2·0-3·3] in the ICD group and 1·2 years [0·8-2·7] in the control group), 138 (14%) patients died in the ICD group and 64 (16%) patients died in the control group. We noted a 43% reduction in mortality in the ICD group compared with the control group (adjusted hazard ratio [HR] 0·57 [95% CI 0·41-0·79]; p=0·0008). Periodic repolarisation dynamics significantly predicted the treatment effect of ICDs on mortality (adjusted p=0·0307). The mortality benefits associated with ICD implantation were greater in patients with periodic repolarisation dynamics of 7·5 deg or higher (n=199; adjusted HR 0·25 [95% CI 0·13-0·47] for the ICD group vs the control group; p<0·0001) than in those with periodic repolarisation dynamics less than 7·5 deg (n=1166; adjusted HR 0·69 [95% CI 0·47-1·00]; p=0·0492; pinteraction=0·0056). The number needed to treat was 18·3 (95% CI 10·6-4895·3) in patients with periodic repolarisation dynamics less than 7·5 deg and 3·1 (2·6-4·8) in those with periodic repolarisation dynamics of 7·5 deg or higher. INTERPRETATION: Periodic repolarisation dynamics predict mortality reductions associated with prophylactic implantation of ICDs in contemporarily treated patients with ischaemic or non-ischaemic cardiomyopathy. Periodic repolarisation dynamics could help to guide treatment decisions about prophylactic ICD implantation. FUNDING: The European Community's 7th Framework Programme.

The Formation and Therapeutic Update of Tumor-Associated Macrophages in Cervical Cancer.

Both clinicopathological and experimental studies have suggested that tumor-associated macrophages (TAMs) play a key role in cervical cancer progression and are associated with poor prognosis in the respects of tumor cell proliferation, invasion, angiogenesis, and immunosuppression. Therefore, having a clear understanding of TAMs is essential in treating this disease. In this review, we will discuss the origins and categories of macrophages, the molecules responsible for forming and reeducating TAMs in cervical cancer (CC), the biomarkers of macrophages and the therapy development targeting TAMs in CC research.

Effects of smoking status, history and intensity on heart rate variability in the general population: The CHRIS study.

BACKGROUND: Heart rate variability (HRV) reflects the autonomous nervous system modulation on heart rate and is associated with several pathologies, including cardiac mortality. While mechanistic studies show that smoking is associated with lower HRV, population-based studies present conflicting results. METHODS: We assessed the mutual effects of active smoking status, cumulative smoking history, and current smoking intensity, on HRV among 4751 adults from the Cooperative Health Research In South Tyrol (CHRIS) study. The HRV metrics standard deviation of normal-to-normal (NN) inter-beat intervals (SDNN), square root of the mean squared differences of consecutive NN intervals (RMSSD), total power (TP), low (LF) and high frequency (HF) power, and their ratio (LF/HF), were derived from 20-minute electrocardiograms. Smoking status, pack-years (PY), and tobacco grams/day from standardized questionnaires were the main exposures. We fitted linear mixed models to account for relatedness, non-linearity, and moderating effects, and including fractional polynomials. RESULTS: Past smokers had higher HRV levels than never smokers, independently of PY. The association of HRV with current smoking became apparent when accounting for the interaction between smoking status and PY. In current smokers, but not in past smokers, we observed HRV reductions between 2.0% (SDNN) and 4.9% (TP) every 5 PY increase. Furthermore, current smokers were characterized by dose-response reductions of 9.8% (SDNN), 8.9% (RMSSD), 20.1% (TP), 17.7% (LF), and 19.1% (HF), respectively, every 10 grams/day of smoked tobacco, independently of common cardiometabolic conditions and HRV-modifying drugs. The LF/HF ratio was not associated with smoking status, history, or intensity. CONCLUSIONS: Smoking cessation was associated with higher HRV levels. In current smokers, heavier smoking intensity appears gradually detrimental on HRV, corroborating previous evidence. By affecting both the sympathetic and parasympathetic nervous system indexes, but not the LF/HF balance, smoking intensity seems to exert a systemic dysautonomic effect.