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BACKGROUND: Exposure to environmental chemicals has been associated with an elevated risk of heart failure (HF). However, the impact on early markers of HF, such as left ventricular dysfunction (LVD), remains limited. OBJECTIVE: To establish a foundation of evidence regarding early HF markers and their association with environmental pollutants, a systematic review and meta-analysis was conducted. METHODS: The search, conducted on October 13th, 2023, encompassed PubMed, Embase, and Web of Science without filters, focusing on observational studies reporting myocardial geometrical, structural, or functional alterations in individuals without a history of heart disease. This included the general adult population, workers, young people, and the elderly. The risk of bias was assessed using the ROBINS-I tool at both study and item levels. RESULTS: The systematic review included 17 studies involving 43.358 individuals exposed to air pollution and 2038 exposed to heavy metals. Approximately 41% of the effect measures of associations reported significant abnormalities in myocardial structure or function. The metanalyses by pollutants categories indicated positive associations between LV systolic and diastolic abnormalities and exposure to PM2.5 [-0.069 (-0.104, -0.033); -0.044 (-0.062, -0.025)] and PM10 [-0.055 (-0.087, -0.022); -0.030 (-0.050, -0.010)] and NO2 [-0.042 (-0.071, -0.013); -0.021 (-0.037, -0.004)], as well as positive associations between lead exposure and LV systolic abnormalities [-0.033 (-0.051, -0.016)]. CONCLUSIONS: Existing evidence shows that specific early markers of HF may be associated with exposure to chemical pollutants. It is recommended to include such endpoints in new longitudinal and case-control studies to confirm further risk associations. These studies should consider co-exposures, account for vulnerable groups, and identify cardiotoxic compounds that may require regulation. When examining the link between myocardial abnormalities and environmental exposure, it is also advisable to explore the supportive use of Adverse Outcome Pathway (AOP) approaches to confirm a causal relationship.
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Exposição Ambiental , Poluentes Ambientais , Disfunção Ventricular Esquerda , Humanos , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/epidemiologia , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidadeRESUMO
OBJECTIVES: Previous studies have shown that depression is associated with mortality in patients with cancer. Depression is however a heterogeneous construct and it may be more helpful to look at different (clusters) of depressive symptoms than to look at depression as a discrete condition. The aim of the present study is to investigate whether clusters of depressive symptoms can be identified using advanced statistics and to investigate how these symptom clusters are associated with all-cause mortality in a large group of patients with cancer. METHOD: Data from a large population-based cohort study (PROFILES) including various cancer types were used. Eligible patients completed self-report questionnaires (i.e. Fatigue assessment scale, Hospital anxiety and depression scale, EORTC QOL-C30) after diagnosis. Survival status was determined on 31 January 2022. RESULTS: In total, 9744 patients were included. Network analyses combining different community detection algorithms showed that clusters of depressive symptoms could be detected that correspond with motivational anhedonia, consummatory anhedonia and negative affect. Survival analyses using the variables that represented these clusters best showed that motivational and consummatory anhedonia were associated with survival. Even after controlling for clinical and sociodemographic variables items assessing motivational anhedonia were significantly associated with mortality over time. CONCLUSION: Separate clusters of symptoms that correspond with motivational and consummatory anhedonia and negative affect can be distinguished and anhedonia may be associated with mortality more than negative affect. Looking at particular (clusters of) depressive symptoms may be more informative and clinically relevant than using depression as a single construct (i.e. syndrome).
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Sobreviventes de Câncer , Neoplasias , Humanos , Depressão/complicações , Anedonia , Taxa de Sobrevida , Qualidade de Vida , Estudos Prospectivos , Estudos de CoortesRESUMO
INTRODUCTION: Hospital admissions for heart failure (HF) are frequent and pose a heavy burden on health care resources. Currently, the decision to hospitalise is based on clinical judgement rather than on prognostic risk stratification. The Emergency Heart failure Mortality Risk Grade (EHMRG) was recently developed to identify high-risk HF patients in the emergency department (ED). OBJECTIVE: To assess the ability of the EHMRG to predict 30-day mortality in Dutch HF patients visiting the ED and to evaluate whether the EHMRG could help to reduce the number of hospital admissions for decompensated HF. METHODS: Patients visiting the ED for decompensated HF were included. The decision to hospitalise or discharge was based on clinical judgement. The EHMRG was calculated retrospectively. Based on their EHMRG, patients were stratified as very low risk, low risk, intermediate risk, high risk and very high risk. RESULTS: In 227 patients (age 73⯱ 12 years, 69% male) 30-day mortality was 11%. Mortality differed significantly among the EHMRG risk groups at 7day (pâ¯= 0.012) and 30-day follow-up (pâ¯< 0.01). Based on clinical judgement, 76% of patients were hospitalised. If decision-making had been based on EHMRG, the hospitalisation rate could have been reduced to 66% (pâ¯< 0.01), particularly by reducing hospitalisations in patients at low risk of death. Mortality in discharged patients, whether the decision was based on EHMRG or clinical judgement, was 0%. CONCLUSION: The EHMRG accurately differentiates between high- and low-risk decompensated HF patients visiting the ED, making it a promising tool to safely reduce the number of HF admissions.
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INTRODUCTION: Identifying ST-elevation myocardial infarction (STEMI) patients who can be referred back to the general practitioner (GP) can improve patient-tailored care. However, the long-term prognosis of patients who are returned to the care of their GP is unknown. Therefore, the aim of this study was to assess the long-term prognosis of patients referred back to the GP after treatment in accordance with a 1-year institutional guideline-based protocol. METHODS: All consecutive patients treated between February 2004 up to May 2013 who completed the 1year institutional MISSION! Myocardial Infarction (MI) follow-up and who were referred to the GP were evaluated. After 1 year of protocolised monitoring, asymptomatic patients with a left ventricular ejection fraction >45% on echocardiography were referred to the GP. Long-term prognosis was assessed with Kaplan-Meier curves and Cox proportional hazards analysis was used to identify independent predictors for 5year all-cause mortality and major adverse cardiovascular events (MACE). RESULTS: In total, 922 STEMI patients were included in this study. Mean age was 61.6⯱ 11.7 years and 74.4% were male. Median follow-up duration after the 1year MISSION! MI follow-up was 4.55 years (interquartile range [IQR] 2.28-5.00). The event-free survival was 93.2%. After multivariable analysis, age, not using an angiotensin-converting enzyme (ACE) inhibitor/angiotensin-II (AT2) antagonist and impaired left ventricular function remained statistically significant predictors for 5year all-cause mortality. Kaplan-Meier curves revealed that 80.3% remained event-free for MACE after 5 years. Multivariable predictors for MACE were current smoking and a mitral regurgitation grade ≥2. CONCLUSION: STEMI patients who are referred back to their GP have an excellent prognosis after being treated according to the 1year institutional MISSION! MI protocol.
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BACKGROUND: Following a train derailment, several tons of acrylonitrile (ACN) exploded, inflamed and part of the ACN ended up in the sewage system of the village of Wetteren. More than 2000 residents living in the close vicinity of the accident and along the sewage system were evacuated. A human biomonitoring study of the adduct N-2-cyanoethylvaline (CEV) was carried out days 14-21 after the accident. OBJECTIVES: (1) To describe the short-term health effects that were reported by the evacuated residents following the train accident, and (2) to explore the association between the CEV concentrations, extrapolated at the time of the accident, and the self-reported short-term health effects. METHODS: Short-term health effects were reported in a questionnaire (n=191). An omnibus test of independence was used to investigate the association between the CEV concentrations and the symptoms. Dose-response relationships were quantified by Generalized Additive Models (GAMs). RESULTS: The most frequently reported symptoms were local symptoms of irritation. In non-smokers, dose-dependency was observed between the CEV levels and the self-reporting of irritation (p=0.007) and nausea (p=0.007). Almost all non-smokers with CEV concentrations above 100pmol/g globin reported irritation symptoms. Both absence and presence of symptoms was reported by non-smokers with CEV concentrations below the reference value and up to 10 times the reference value. Residents who visited the emergency services reported more symptoms. This trend was seen for the whole range of CEV concentrations, and thus independently of the dose. DISCUSSION AND CONCLUSION: The present study is one of the first to relate exposure levels to a chemical released during a chemical incident to short-term (self-reported) health effects. A dose-response relation was observed between the CEV concentrations and the reporting of short-term health effects in the non-smokers. Overall, the value of self-reported symptoms to assess exposure showed to be limited. The results of this study confirm that a critical view should be taken when considering self-reported health complaints and that ideally biomarkers are monitored to allow an objective assessment of exposure.
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Acrilonitrila/toxicidade , Vazamento de Resíduos Químicos , Irritantes/toxicidade , Ferrovias , Adulto , Bélgica , Cotinina/urina , Relação Dose-Resposta a Droga , Monitoramento Ambiental , Feminino , Cefaleia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Autorrelato , Fumar/sangue , Fumar/urina , Inquéritos e Questionários , Tremor/induzido quimicamente , Valina/análogos & derivados , Valina/sangueRESUMO
AIM: Colorectal cancer (CRC) screening programmes detect early cancers but unfortunately have limited sensitivity and specificity. Mass spectrometry-based determination of serum peptide and protein profiles provides a new approach for improved screening. METHOD: Serum samples were obtained from 126 CRC patients before treatment and 277 control individuals. An additional group of samples from 50 CRC patients and 82 controls was used for validation. Peptide and protein enrichments were carried out using reverse-phase C18 and weak-cation exchange magnetic beads in an automated solid-phase extraction and spotting procedure. Profiles were acquired on a matrix-assisted laser desorption/ionization time-of-flight system. Discriminant rules using logistic regression were calibrated for the peptide and protein signatures separately, followed by combining the classifications to obtain double cross-validated predicted class probabilities. Results were validated on an identical patient set. RESULTS: A discriminative power was found for patients with CRC representative for all histopathological stages compared with controls with an area under the curve of 0.95 in the test set (0.93 for the validation set) and with a high specificity (94-95%). CONCLUSION: The study has shown that a serum peptide and protein biomarker signature can be used to distinguish CRC patients from healthy controls with high discriminative power. This relatively simple and cheap test is promising for CRC screening.
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Biomarcadores Tumorais/sangue , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Proteômica , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Residents and staff of nursing homes are important target groups for influenza vaccination in Germany. The aim of this study was to gain the first insights into whether nursing homes organize activities with respect to vaccination against influenza and whether there is a demand for further information. In the context of the national influenza immunization campaign-which is jointly carried out by the Robert Koch Institute (RKI) and the Federal Centre for Health Education (BZgA) on an annual basis-influenza information kits were sent to the management of 10,700 nursing homes in September 2013. Along with the information material, the institutions also received a questionnaire to which they were able to respond via mail, fax, or online. Data from 988 homes were included in the analysis. The majority of institutions informed both residents (88.9 %) and nursing staff (81.2 %) about influenza vaccination. However, only 64.7 % of nursing homes carried out specific immunization activities for their residents and only half (49.3 %) offered a flu shot to their staff. When asked why the institutions do not provide influenza-specific information and vaccination to their staff, the majority had the opinion that this is the responsibility of each individual's general practitioner. Overall, only 4.9 % of nursing homes assessed influenza vaccination coverage among their staff annually. A third of all surveyed institutions (33.6 %) expressed a demand for additional influenza vaccine-related information. In conclusion, improved health education is needed to raise awareness about the importance of influenza vaccination among residents and employees of nursing homes in Germany so as to prevent influenza-associated morbidity and mortality in this risk group.
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Promoção da Saúde/estatística & dados numéricos , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Avaliação das Necessidades , Enfermeiras e Enfermeiros/estatística & dados numéricos , Casas de Saúde/estatística & dados numéricos , Vacinação/estatística & dados numéricos , Adulto , Idoso , Feminino , Alemanha/epidemiologia , Pesquisas sobre Atenção à Saúde , Humanos , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Padrões de Prática em Enfermagem/estatística & dados numéricosRESUMO
We performed an in vitro evaluation of the genotoxic potential of water extracts from four Hypoxis species (Hypoxis hemerocallidea, H. colchicifolia, H. rigidula, H. acuminata) and a commercial preparation thereof using the neutral red uptake (NRU) assay, the alkaline comet assay and the cytome assay in human hepatoma HepG2 cells. The relative cytotoxicity of these samples was established by determining their NI50 values (50% inhibition of NRU), and these results were used for dose-finding in genotoxicity tests. None of the tested extracts were identified as genotoxic in both the alkaline comet assay and cytome assay.
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Dano ao DNA , Hypoxis/toxicidade , Mutagênicos/toxicidade , Extratos Vegetais/toxicidade , Ensaio Cometa , Humanos , Testes de MutagenicidadeRESUMO
Achievement of the goal to eliminate measles by 2015 set by the European region of the World Health Organization (WHO) necessitates an increase in the willingness of German nationals to get vaccinated. To identify influential factors on vaccination behavior as the basis for communication measures specific to target groups, the Federal Centre for Health Education (BZgA) has conducted two representative surveys on attitude, knowledge, and practice concerning vaccination among parents of children between 0 and 13 years as well as among adolescents and adults. The parents' survey (n = 3,002) revealed that more than one-third see measles as a harmless disease. The survey of adolescents and adults (n = 4,483, 16-85 years) also shows that about one-quarter of the interviewees between 16 and 44 years regarded vaccination against measles as not very important. Moreover, 81 % of adults born after 1970 without sufficient existing vaccine protection were not aware of the new measles vaccination recommendation for this age group. Personal consultation with the physician was regarded as the major source of vaccination information in both surveys. About half of all persons interviewed intended to obtain information about vaccinations on the Internet. The results of these studies were used for the development of a nationwide multilevel BZgA campaign on vaccination protection against measles, its goal being to support medical professionals with comprehensive information and to enable adolescents and young adults via different communication measures to make well-informed vaccination decisions.
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Educação em Saúde/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Letramento em Saúde/estatística & dados numéricos , Vacinação em Massa/estatística & dados numéricos , Sarampo/epidemiologia , Sarampo/prevenção & controle , Pais/educação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Alemanha/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
PURPOSE: Limited or absent axial rotation of the mobile insert of total knee prostheses could lead to high contact stresses and stresses at the bone-implant interface, which in turn might lead to implant loosening. The aim of this study was to assess knee kinematics and muscle activation and their possible change over time in patients with a highly congruent, mobile-bearing total knee prosthesis. METHODS: A prospective series of 11 rheumatoid arthritis patients was included to participate in this fluoroscopic and EMG study; only 7 patients completed the study. Kinematic evaluations took place 7 months, 1 and 2 years post-operatively. Repeated measurements ANOVA and linear mixed-effects model for longitudinal data were used to compare the differences between the follow-ups. RESULTS: There are no significant changes in axial rotations between follow-up moments for the femoral component as well as the mobile insert. The insert remained mobile and followed the femoral component from 0° until approximately 60° of knee flexion. Diverging and reversed axial rotations and translations were seen during the dynamic motions. CONCLUSIONS: Knee kinematics and muscle activation do not appear to change in the first 2 post-operative years. Reversed and divergent axial rotations with increasing knee flexion indicate that as soon as the congruency decreases, the femoral component is no longer forced in a certain position by the insert and moves to a self-imposed position. At lower knee flexion angles, the femoral component might be obstructed by the highly congruent insert and therefore might not be able to move freely. LEVEL OF EVIDENCE: Therapeutic study, Level IV.
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Artrite Reumatoide/cirurgia , Artroplastia do Joelho/instrumentação , Articulação do Joelho/cirurgia , Prótese do Joelho , Desenho de Prótese , Idoso , Fenômenos Biomecânicos , Eletromiografia , Feminino , Fluoroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Amplitude de Movimento ArticularRESUMO
The regulatory landscape of flavorings is evolving, thereby putting pressure on control laboratories to develop analytical methods for a wide range of compounds in various types of food and drinks. In order to improve the monitoring of flavoring substances, a versatile and accurate analytical method using the solvent-assisted flavor evaporation (SAFE) technique coupled to GC-MS(SIM) was developed and validated. Focus was put on authorized flavoring substances requiring specific attention due to a genotoxic concern based on information from European risks assessment reports. Thirty-seven (suspected) genotoxic flavoring substances were analyzed in a selection of ten alcohol-free beers. Five suspected genotoxic compounds (i.e. 1-(2-furyl)-2-propanone, 2-acetylfuran, 2-acetyl-5-methylfuran, 2-acetyl-3,5-dimethylfuran, hex-2-eno-1,4-lactone) as well as two confirmed genotoxic flavoring substances (p-mentha-1,8-dien-7-al, 2,4-pentanedione) were identified and quantified among the selected samples. Low concentrations and natural occurrences of the identified compounds suggested that these were not added as such but rather originated from heat-treatments or from plant-based extracts.
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Cerveja , Aromatizantes , Bélgica , Dano ao DNA , Aromatizantes/análise , Cromatografia Gasosa-Espectrometria de MassasRESUMO
Evaluating the migration of chemicals from food contact materials (FCM) into food is a key step in the safety assessment of such materials. In this paper, a simple mechanistic model describing the migration of chemicals from FCM to food was combined with quantitative property-property relationships (QPPRs) for the prediction of diffusion coefficients and FCM-Food partition coefficients. The aim of the present study was to evaluate the performance of these operational models in the prediction of a chemical's concentration in food in contact with a plastic monolayer FCM. A comparison to experimental migration values reported in literature was conducted. Deterministic simulations showed a good match between predicted and experimental values. The tested models can be used to provide insights in the amount and the type of toxicological data that are needed for the safety evaluation of the FCM substance. Uncertainty in QPPRs used for describing the processes of both diffusion in FCM and partition at the FCM-Food interface was included in the analysis. Combining uncertainty in QPPR predictions, it was shown that the third quartile (75th percentile) derived from probabilistic calculations can be used as a conservative value in the prediction of chemical concentration in food, with reasonable safety factors.
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Contaminação de Alimentos , Embalagem de Alimentos , Difusão , Contaminação de Alimentos/análise , Neurofibromina 2 , Plásticos/análiseRESUMO
BACKGROUND: Radiologic evaluation of adults with febrile urinary tract infection (UTI) is frequently performed to exclude urological disorders. This study aims to develop a clinical rule predicting need for radiologic imaging. METHODS: We conducted a prospective, observational study including consecutive adults with febrile UTI at 8 emergency departments (EDs) in the Netherlands. Outcomes of ultrasounds and computed tomographs of the urinary tract were classified as "urgent urological disorder" (pyonephrosis or abscess), "nonurgent urologic disorder," "normal," and "incidental nonurological findings." Urgent and nonurgent urologic disorders were classified as "clinically relevant radiologic findings." The data of 5 EDs were used as the derivation cohort, and 3 EDs served as the validation cohort. RESULTS: Three hundred forty-six patients were included in the derivation cohort. Radiologic imaging was performed for 245 patients (71%). A prediction rule was derived, being the presence of a history of urolithiasis, a urine pH ≥7.0, and/or renal insufficiency (estimated glomerular filtration rate, ≤40 mL/min/1.73 m(3)). This rule predicts clinically relevant radiologic findings with a negative predictive value (NPV) of 93% and positive predictive value (PPV) of 24% and urgent urological disorders with an NPV of 99% and a PPV of 10%. In the validation cohort (n = 131), the NPV and PPV for clinically relevant radiologic findings were 89% and 20%, respectively; for urgent urological disorders, the values were 100% and 11%, respectively. Potential reduction of radiologic imaging by implementing the prediction rule was 40%. CONCLUSIONS: Radiologic imaging can selectively be applied in adults with febrile UTI without loss of clinically relevant information by using a simple clinical prediction rule.
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Febre/etiologia , Infecções Urinárias/diagnóstico por imagem , Infecções Urinárias/etiologia , Sistema Urinário/anormalidades , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Ultrassonografia , Sistema Urinário/patologia , Infecções Urinárias/patologiaRESUMO
Polycyclic aromatic hydrocarbons (PAH) are a complex group of organic compounds, consisting of at least three fused aromatic rings, which are formed during combustion of organic matter. While some PAHs have been reported to have carcinogenic and/or mutagenic properties, another possible negative health impact is their endocrine disrupting potential. Therefore, the aim of this study was to determine both the agonistic and antagonistic endocrine activity of 9 environmentally relevant PAHs using three different CALUX bioassays: The AhR-CALUX, The ERα-CALUX and PPARγ-CALUX. For the PPARγ-CALUX anthracene, fluoranthene, pyrene and fluorene showed weak agonistic activity, whilst benzo(a)pyrene (B(a)P) was the only one exhibiting weak antagonistic activity. For the AhR-CALUX, chrysene was the only PAH that showed relatively strong agonist activity (except for B(a)P which was used as a standard). Pyrene, anthracene and fluoranthene showed weak AhR agonist activity. In the ERα-CALUX bioassay, fluoranthene had agonistic activity whilst B(a)P exhibited both agonistic and antagonistic activity (lowering E2 activity by 30%). Phenanthrene and anthracene had weak ERα agonist activities. These results indicate that certain PAHs have multiple modes of action and can activate/inhibit multiple receptor signaling pathways known to play critical roles in mediating endocrine disruption.
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Receptor alfa de Estrogênio/agonistas , PPAR gama/agonistas , Hidrocarbonetos Policíclicos Aromáticos/farmacologia , Receptores de Hidrocarboneto Arílico/agonistas , Transdução de Sinais/efeitos dos fármacos , Animais , Bioensaio , Linhagem Celular Tumoral , Receptor alfa de Estrogênio/antagonistas & inibidores , Humanos , Camundongos , PPAR gama/antagonistas & inibidores , Ratos , Receptores de Hidrocarboneto Arílico/antagonistas & inibidoresRESUMO
BACKGROUND AND AIMS: Sigmoid diverticular disease has great clinical importance due to its increasing incidence in the Western world and a broad spectrum of clinical features with potential fatal complications after surgery. The definition of risk factors associated with postoperative infections, surgical complications and mortality could be helpful in clinical decision-making and optimizing perioperative treatment. MATERIALS AND METHODS: Based on a prospective database, 168 consecutive patients undergoing surgery for sigmoid diverticulitis were included in this study. The association of different potential risk factors such as age, Hinchey classification, type and duration of operation, surgeons' experience, blood loss, comorbidities, and hospital course with perioperative complications and mortality were tested by univariate and multivariate analysis. RESULTS: Of the 168 patients enrolled in this study, there were 84 male and 84 female. A third of patients were operated as emergency cases (within 24 h after surgical evaluation); 62% underwent open surgery, 35% were treated laparoscopically with a conversion rate of 3%. A blood transfusion received 14% of patients, a surgical infection occurred in 20%, surgical complications appeared in 24% with a necessity for re-exploration in 9.5%. Leakage of the primary anastomosis was seen in 3.3%, whereas a leakage of the Hartmann's stump occurred in 4.3%. Overall in-hospital mortality was 4.1%. Multivariate analysis demonstrated Hinchey classification and intraoperative blood transfusion to be independently associated with postoperative infections, complications and mortality. CONCLUSION: Hinchey classification and intraoperative blood transfusion are independently associated with a worse perioperative outcome in patients undergoing surgery for sigmoid diverticular disease. While Hinchey classification cannot be influenced per se by the surgeon, outcome might be influenced by reducing the need for intraoperative blood transfusion.
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Colo Sigmoide/cirurgia , Diverticulite/mortalidade , Diverticulite/cirurgia , Complicações Pós-Operatórias/mortalidade , Idoso , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de RiscoRESUMO
OBJECTIVES: Clostridioides difficile infection (CDI) has become the main cause of nosocomial infective diarrhoea. To survey and control the spread of different C. difficile strains, there is a need for suitable rapid tests. The aim of this study was to identify peptide/protein markers for the rapid recognition of C. difficile strains by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). METHODS: We analysed 44 well-characterized strains, belonging to eight different multi-locus sequence types (MLST), using ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) MS. The amino acid sequence of two peptide markers specific for MLST-1 and MLST-11 strains was elucidated by MALDI-TOF-MS/MS. The investigation of 2689 C. difficile genomes allowed the determination of the sensitivity and specificity of these markers. C18-solid-phased extraction was used to enrich the MLST-1 marker. RESULTS: Two peptide markers (m/z 4927.81 and m/z 5001.84) were identified and characterized for MLST-1 and MLST-11 strains, respectively. The MLST-1 marker was found in 786 genomes of which three did not belong to MLST-1. The MLST-11 marker was found in 319 genomes, of which 14 did not belong to MLST-11. Importantly, all MLST-1 and MLST-11 genomes were positive for their respective marker. Furthermore, a peptide marker (m/z 5015.86) specific for MLST-15 was found in 59 genomes. We translated our findings into a fast and simple method that allowed the unambiguous identification of the MLST-1 marker on a MALDI-TOF-MS platform. CONCLUSIONS: MALDI-FTICR MS-based peptide profiling resulted in the identification of peptide markers for C. difficile MLST-1 and MLST-11.
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Clostridioides difficile/classificação , Tipagem de Sequências Multilocus , Peptídeos/genética , Técnicas de Tipagem Bacteriana , Biomarcadores/análise , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/microbiologia , Genoma Bacteriano , Humanos , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Stress-system dysregulation is thought to increase the risk for anxiety disorders. Here we describe both hypothalamic pituitary adrenal (HPA) axis and autonomic nervous system (ANS) activity in basal non-challenging conditions and after 0.5mg dexamethasone in generalized social anxiety disorder (gSAD) patients. To ensure stress-free sampling we collected saliva and determined cortisol and alpha-amylase (sAA), the latter a relative new marker of autonomic activity. Forty-three untreated gSAD patients without comorbidity were compared with 43 age and gender matched controls in non-stressed conditions on sAA and cortisol after awakening, during the day (including late evening), and after a low dose (0.5mg) of dexamethasone. Cortisol and sAA were analyzed with mixed models. Additional analyses were done with paired t-tests. Apart from the assessments in the morning, gSAD patients had significantly higher diurnal and post-dexamethasone 1600h sAA levels. No differences between gSAD and controls in any cortisol measurements were found. In conclusion, in gSAD in basal, non-stimulated conditions and after dexamethasone, we found hyperactivity of the ANS, as measured with sAA, but not of the HPA-axis. This suggests a relative increased activity of the ANS as compared to the HPA-axis, in line with the observed hyperarousal in gSAD.
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Agorafobia/metabolismo , Transtornos de Ansiedade/metabolismo , Hidrocortisona/sangue , alfa-Amilases/metabolismo , Adulto , Agorafobia/sangue , Agorafobia/psicologia , Anti-Inflamatórios/farmacologia , Transtornos de Ansiedade/sangue , Transtornos de Ansiedade/psicologia , Sistema Nervoso Autônomo/fisiopatologia , Ritmo Circadiano/fisiologia , Dexametasona/farmacologia , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/fisiopatologia , Saliva/metabolismoRESUMO
In this study, a sensitive and selective method based on liquid chromatography combined with diode array and tandem mass spectrometry detection (LC-DAD-MS/MS) was developed for the simultaneous quantitative determination of fenofibric acid, pravastatin and its main metabolites in human plasma. In this method, an automated solid-phase extraction (SPE) on disposable extraction cartridges (DECs) is used to isolate the compounds from the biological matrix and to prepare a cleaner sample before injection and analysis in the LC-DAD-MS/MS system. On-line LC-DAD-MS/MS system using an atmospheric pressure ionization (TurboIonSpray) was then developed for the simultaneous determination of pravastatin, 3-hydroxy isomeric metabolite (3-OH metab), pravalactone and fenofibric acid. The separation is obtained on an endcapped dodecyl silica based stationary phase using a mobile phase consisting of a mixture of acetonitrile, methanol and 5mM ammonium acetate solution (30:30:40, v/v/v). Sulindac and triamcinolone were used as internal standards (ISs). The detection of the fenofibric acid and sulindac was achieved by means of a DAD system. The MS/MS ion transitions monitored were m/z 442.2-->269.1, 442.2-->269.1, 424.3-->183.0 and 435.2-->397.2 for pravastatin, 3-OH metab, pravalactone and triamcinolone, respectively. The method was validated regarding stability, selectivity, extraction efficiency, response function, trueness, precision lower limit of quantitation and matrix effect. The limits of quantitation (LOQs) were around 0.50 ng/ml for pravastatin, 0.25 ng/ml for 3-OH metab, 0.05 ng/ml for pravalactone and 0.25 microg/ml for fenofibric acid.
Assuntos
Cromatografia Líquida/métodos , Fenofibrato/análogos & derivados , Pravastatina/sangue , Espectrometria de Massas em Tandem/métodos , Fenofibrato/sangue , Fenofibrato/isolamento & purificação , Humanos , Estrutura Molecular , Pravastatina/isolamento & purificação , Reprodutibilidade dos Testes , Extração em Fase SólidaRESUMO
This study focused on the search for new biomarkers based on liquid chromatography-multiple reaction monitoring (LC-MRM) proteomics profiling of whole saliva from patients with periodontitis compared to healthy subjects. The LC-MRM profiling approach is a new and innovative method that has already been validated for the absolute and multiplexed quantification of biomarkers in several diseases. The dataset for this study was produced using LC-MRM to monitor protein levels in a multiplex assay, it provides clinical information on salivary biomarkers of periodontitis. The data presented here is an extension of our recently published research article (Mertens et al., 2017) [1].