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1.
Ann Oncol ; 34(8): 660-669, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37201751

RESUMEN

BACKGROUND: The multicenter, randomized, phase IV, intergroup AGO-B WSG PreCycle trial (NCT03220178) evaluated the impact of CANKADO-based electronic patient-reported outcome (ePRO) assessment on quality of life (QoL) in hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer (MBC) patients receiving palbociclib and an aromatase inhibitor or palbociclib + fulvestrant. CANKADO PRO-React, a European Union-registered medical device, is an interactive autonomous application reacting to patient self-reported observations. PATIENTS AND METHODS: Between 2017 and 2021, 499 patients (median age 59 years) from 71 centers were randomized (2 : 1, stratified by therapy line) between an active version of CANKADO PRO-React (CANKADO-active arm) and a version with limited functionality (CANKADO-inform arm). A total of 412 patients (271 CANKADO-active; 141 CANKADO-inform) were available for analysis of the primary endpoint, time to deterioration (TTD) of QoL [10-point drop on the Functional Assessment of Cancer Therapy-General (FACT-G) score], using an Aalen-Johansen estimator for cumulative incidence function of TTD DQoL (QoL deterioration) with 95% pointwise confidence intervals (CIs). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and DQoL. RESULTS: In all patients [intention-to-treat (ITT)-ePRO], cumulative incidence of DQoL was significantly more favorable (lower) in the CANKADO-active arm (hazard ratio 0.698, 95% CI 0.506-0.963). Among first-line patients (n = 295), the corresponding hazard ratio was 0.716 (0.484-1.060; P = 0.09), and in second-line patients (n = 117) it was 0.661 (0.374-1.168; P = 0.2). Absolute patient numbers declined in later visits; FACT-G completion rates were 80% and higher until about visit 30. Mean FACT-G scores showed a steady decline from baseline and an offset in favor of CANKADO-active. No significant differences in clinical outcome were observed between arms: median PFS (ITT population) was 21.4 (95% CI 19.4-23.7) (CANKADO-active) and 18.7 (15.1-23.5) months (CANKADO-inform); median OS was not reached (CANKADO-active) and 42.6 months (CANKADO-inform). CONCLUSIONS: PreCycle is the first multicenter randomized eHealth trial demonstrating a significant benefit for MBC patients receiving oral tumor therapy when using an interactive autonomous patient empowerment application.


Asunto(s)
Neoplasias de la Mama , Humanos , Persona de Mediana Edad , Femenino , Neoplasias de la Mama/patología , Calidad de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Piridinas/uso terapéutico , Receptor ErbB-2/metabolismo
2.
Subst Use Misuse ; 58(11): 1438-1446, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37331791

RESUMEN

Objective: Using the negative reinforcement and common factors frameworks, this work assessed whether and how anxiety sensitivity, distress tolerance, and impulsivity relate to reasons for drinking (RFD) in a residential treatment sample with co-occurring alcohol use disorder and posttraumatic stress disorder (AUD-PTSD). Demographic differences were also examined. Method: Participants were 75 (52.0% male, 78.7% white) adults at a residential substance use treatment facility who met criteria for AUD-PTSD with 98.67% meeting criteria for one or more substance use disorders in addition to AUD. Participants completed measures of anxiety sensitivity, distress tolerance, impulsivity, RFD, and AUD-PTSD symptoms. Univariate and multivariate linear regression was used with and without controlling for demographic variables (i.e., age, race, and sex). Results: The positive and negative urgency facets of impulsivity were positively related to both negative affect and cue/craving response RFD with relations maintained after controlling for demographic variables and including PTSD symptom severity (ßs .30-.51). There were no significant relations between impulsivity and social RFD. No facets of anxiety sensitivity or distress tolerance were significantly related to RFD domains. Conclusions: Findings suggest that the urgency facets of impulsivity are crucial in understanding negative affect and cue/craving RFD. However, anxiety sensitivity and distress tolerance are not related to RFD in this dually diagnosed AUD-PTSD sample. Treatment considerations and future directions are discussed.


Asunto(s)
Alcoholismo , Trastornos por Estrés Postraumático , Trastornos Relacionados con Sustancias , Adulto , Humanos , Masculino , Femenino , Trastornos por Estrés Postraumático/complicaciones , Trastornos por Estrés Postraumático/terapia , Ansiedad , Trastornos de Ansiedad , Consumo de Bebidas Alcohólicas , Alcoholismo/complicaciones , Alcoholismo/terapia , Trastornos Relacionados con Sustancias/complicaciones
3.
Ann Surg Oncol ; 27(3): 637-644, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31900808

RESUMEN

INTRODUCTION: Pathologic complete response (pCR) after neoadjuvant chemotherapy has a demonstrated survival advantage; however, outcomes for non-pCR by receptor status are less understood. We sought to evaluate survival and distant recurrence by receptor status for patients with residual stage II/III breast cancer. METHODS: A stage-stratified random sample of 11,366 patients with stage II-III breast cancer in 2006-2007 was selected from 1217 facilities in the National Cancer Database for a Commission on Cancer Special Study. We identified patients with residual pathologic stage II/III cancer who received standard of care therapy based on receptor status. Distant recurrence and 5-year survival were abstracted and Kaplan-Meier curves were generated by receptor status. Multivariable Cox regression was used to estimate hazard ratios for death and distant recurrence. RESULTS: A total of 734 patients had residual disease; 58%, 28%, and 14% were ER or PR+/Her2neu-, ER and PR-/Her2neu-, and Her2neu+ (any ER/PR), respectively. ER and PR-/Her2neu- cancers had the poorest 5-year overall (52% vs. 82% for Her2neu+ and ER or PR+/Her2neu-, p < 0.0001) and distant recurrence-free survival (57% vs. 72% Her2neu+ and 77% ER or PR+/Her2neu, p < 0.0001). Cox regression models demonstrated a higher likelihood of distant recurrence and death for patients with ER and PR-/Her2neu- disease (HR 2.25, 95% CI 1.56-3.24 and HR 3.19, 95% CI 2.20-4.64 respectively) compared with ER or PR+/Her2neu-. CONCLUSIONS: Patients with residual ER and PR-/Her2neu- cancer have a significant risk of distant recurrence and mortality compared with other breast cancer types, supporting the consideration for additional adjuvant therapy and novel clinical trials in this cohort. Trial registry number ClinicalTrials.gov identifier NCT02171078.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/mortalidad , Quimioterapia Adyuvante/mortalidad , Terapia Neoadyuvante/mortalidad , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Tasa de Supervivencia
4.
Eur J Neurol ; 27(8): 1405-1414, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32396653

RESUMEN

BACKGROUND AND PURPOSE: A wide variety of metabolic changes, including an increased incidence of diabetes mellitus (DM) and dyslipidaemia, has been described in amyotrophic lateral sclerosis (ALS). The aim of this study was to investigate the associations of statin use and history of DM with onset of disease and survival in patients with ALS. METHODS: In all, 501 patients (mean age 65.2 ± 10.9 years; 58.5% male) from the ALS Registry Swabia recruited between October 2010 and April 2016 were included in this prospective cohort study. Data were collected using a standardized questionnaire. RESULTS: Statin use (n = 65) was not associated with overall survival (P = 0.62). Age of ALS onset in patients with DM was 4.2 years later (95% confidence interval 1.3-7.2 years) than in patients without DM (P < 0.01). The overall survival of patients with high body mass index at study entry (>27.0 kg/m2 , upper quartile, n = 127) was prolonged by more than 5 months compared to patients with low body mass index (<22.0 kg/m2 , lower quartile, n = 123; P = 0.04). CONCLUSIONS: This study supports the view that statin use is not associated with overall survival of ALS patients, suggesting that statins are not harmful and should not be discontinued in ALS. Furthermore, the delayed onset of ALS in patients with DM may mirror the potentially protective metabolic profile associated with type 2 DM. Consistently, this study provides further evidence that high body mass index is a positive prognostic factor in ALS.


Asunto(s)
Esclerosis Amiotrófica Lateral , Anciano , Esclerosis Amiotrófica Lateral/epidemiología , Diabetes Mellitus/epidemiología , Femenino , Alemania/epidemiología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Sistema de Registros
5.
Anaesthesia ; 75(10): 1301-1306, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32335900

RESUMEN

The current international COVID-19 health crisis underlines the importance of adequate and suitable personal protective equipment for clinical staff during acute airway management. This study compares the impacts of standard air-purifying respirators and powered air-purifying respirators during simulated difficult airway scenarios. Twenty-five anaesthetists carried out four different standardised difficult intubation drills, either unprotected (control), or wearing a standard or a powered respirator. Treatment times and wearer comfort were determined and compared. In the wearer comfort evaluation form, operators rated mobility, noise, heat, vision and speech intelligibility. All anaesthetists accomplished the treatment objectives of all study arms without adverse events. Total mean (SD) intubation times for the four interventions did not show significant differences between the powered and the standard respirator groups, being 16.4 (8.6) vs. 19.2 (5.2) seconds with the Airtraq™; 11.4 (3.4) vs. 10.0 (2.1) seconds with the videolaryngoscope; 39.2 (4.5) vs. 40.1 (4.8) seconds with the fibreoptic bronchoscope scope; and 15.4 (5.7) vs. 15.1 (5.0) seconds for standard tracheal intubation by direct laryngoscopy, respectively. Videolaryngoscopy allowed the shortest intubation times regardless of the respiratory protective device used. Anaesthetists rated heat and vision significantly higher in the powered respirator group; however, noise levels were perceived to be significantly lower than in the standard respirator group. We conclude that standard and powered respirators do not significantly prolong simulated advanced intubation procedures.


Asunto(s)
Manejo de la Vía Aérea/métodos , Dispositivos de Protección Respiratoria , Anestesistas , Estudios Cruzados , Humanos , Laringoscopía , Maniquíes , Factores de Tiempo
6.
N Z Vet J ; 67(5): 264-269, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31234719

RESUMEN

Aims: To investigate the effect of the transverse arytenoid ligament (TAL) on abduction of the arytenoid cartilage when performing laryngoplasty. Methods: Modified prosthetic laryngoplasty was performed on right and left sides of 13 cadaver larynges. Increasing force was sequentially applied to the left arytenoid cartilage at 3 N intervals from 0-24 N, when the force on the right arytenoid cartilage was either 0 or 24 N, before and after TAL transection. Digital photographs of the rostral aspect of the larynx were used to determine the left arytenoid abduction angles for these given force combinations and results compared before and after TAL transection. Longitudinal and transverse sections of the TAL from seven other equine larynges were also examined histologically. Results: Increasing force on the left arytenoid cartilage from 0-24 N produced a progressive increase in the angle of the left arytenoid cartilage (p < 0.001) and increasing force on the right arytenoid cartilage from 0-24 N reduced the angle of the left arytenoid cartilage (p < 0.001). Following transection of the TAL the mean angle of the left arytenoid increased from 36.7 (95% CI = 30.5-42.8)° to 38.4 (95% CI = 32.3-44.5)°. Histological examination showed that the TAL was not a discrete ligament between the arytenoid cartilages but was formed by the convergence of the ligament and the left and right arytenoideus transversus muscles. Conclusions: Transection of the TAL in ex vivo equine larynges enabled greater abduction of the left arytenoid cartilage for a given force. These results indicate that TAL transection in conjunction with prosthetic laryngoplasty may have value, but the efficacy and safety of TAL transection under load in vivo, and in horses clinically affected with recurrent laryngeal neuropathy must be evaluated. Abbreviations: Fmax: Force needed to maximally abduct the left or right arytenoid; TAL: Transverse arytenoid ligament.


Asunto(s)
Cartílago Aritenoides/fisiología , Caballos/fisiología , Laringe/fisiología , Ligamentos/fisiología , Animales , Cartílago Aritenoides/anatomía & histología , Fenómenos Biomecánicos , Cadáver , Enfermedades de los Caballos/cirugía , Traumatismos del Nervio Laríngeo/cirugía , Traumatismos del Nervio Laríngeo/veterinaria , Laringoplastia/métodos , Laringoplastia/veterinaria , Laringe/anatomía & histología , Ligamentos/anatomía & histología , Fotograbar
7.
Mol Psychiatry ; 22(10): 1431-1439, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28167838

RESUMEN

The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes. We therefore performed a genome-wide association study with a dimensional, PD/AG-related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1370 healthy German volunteers of the CRC TRR58 MEGA study wave 1. A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, P=3.3 × 10-8; rs191260602, P=3.9 × 10-8). We followed up on this finding in a larger dimensional ACQ sample (N=2547) and in independent samples with a dichotomous AG phenotype based on the Symptoms Checklist (SCL-90; N=3845) and a case-control sample with the categorical phenotype PD/AG (Ncombined =1012) obtaining highly significant P-values also for GLRB single-nucleotide variants rs17035816 (P=3.8 × 10-4) and rs7688285 (P=7.6 × 10-5). GLRB gene expression was found to be modulated by rs7688285 in brain tissue, as well as cell culture. Analyses of intermediate PD/AG phenotypes demonstrated increased startle reflex and increased fear network, as well as general sensory activation by GLRB risk gene variants rs78726293, rs191260602, rs17035816 and rs7688285. Partial Glrb knockout mice demonstrated an agoraphobic phenotype. In conjunction with the clinical observation that rare coding GLRB gene mutations are associated with the neurological disorder hyperekplexia characterized by a generalized startle reaction and agoraphobic behavior, our data provide evidence that non-coding, although functional GLRB gene polymorphisms may predispose to PD by increasing startle response and agoraphobic cognitions.


Asunto(s)
Agorafobia/genética , Agorafobia/metabolismo , Receptores de Glicina/genética , Adulto , Alelos , Ansiedad/complicaciones , Trastornos de Ansiedad/genética , Encéfalo/metabolismo , Encéfalo/fisiología , Estudios de Casos y Controles , Cognición/fisiología , Miedo/fisiología , Miedo/psicología , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Genotipo , Alemania , Humanos , Masculino , Mutación/genética , Trastorno de Pánico/genética , Receptores de Glicina/metabolismo , Reflejo de Sobresalto/genética
8.
Support Care Cancer ; 26(6): 2015-2022, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29332175

RESUMEN

IMPORTANCE: Significant variation in the number and types of oncologists that provide breast cancer follow-up exists. However, there is limited understanding regarding breast cancer survivors' preferences for who provides their follow-up. Our objective was to explore breast cancer survivors' perspectives on the goals of breast cancer follow-up, the preferred role for primary care providers, and the perceived roles of different types of oncologists during follow-up. METHODS: A convenience sample of stage 0-III breast cancer survivors was identified and in-depth one-on-one interviews conducted. Data were analyzed using inductive content analysis. RESULTS: Survivors cited a strong preference for oncology-based follow-up within the first 5 years after diagnosis, driven by their need for reassurance that cancer had not recurred. Survivors also thought that their primary care provider needed to be involved. Survivors assumed that oncology follow-up was directed by a standard protocol that included streamlining the follow-up team. Survivors recognized that patients with more complex cancers or challenging treatment courses may require more intensive follow-up and deviate from the standard protocol. Most survivors were comfortable deferring decisions regarding who participated in follow-up to the oncology team. CONCLUSIONS: Most patients think a streamlined approach to oncology-based breast cancer follow-up already occurs, driven by a standard protocol. The use of a standard protocol to provide guidance for which types of oncology providers should participate in breast cancer follow-up will streamline care and represents a significant opportunity to reduce unnecessary variation. This approach is especially critical given patients' strong preferences for oncology-based follow-up.


Asunto(s)
Neoplasias de la Mama/terapia , Oncólogos/tendencias , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Supervivientes de Cáncer , Femenino , Humanos , Persona de Mediana Edad
9.
Ann Oncol ; 28(11): 2768-2772, 2017 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-28945833

RESUMEN

BACKGROUND: Response rates in HER2-overexpressing EBC treated with neoadjuvant chemotherapy and trastuzumab (T) have been improved by addition of pertuzumab (P). The prospective, phase II, neoadjuvant WSG-ADAPT HER2+/HR- trial assessed whether patients with strong early response to dual blockade alone might achieve pathological complete response (pCR) comparable to that of patients receiving dual blockade and chemotherapy. PATIENTS AND METHODS: Female patients with HER2+/HR- EBC (M0) were randomized (5:2) to 12 weeks of T + P ± weekly paclitaxel (pac) at 80 mg/m2. Early response was defined as proliferation decrease ≥30% of Ki-67 (versus baseline) or low cellularity (<500 invasive tumor cells) in the 3-week biopsy. The trial was designed to test non-inferiority for pCR in early responding patients of the T + P arm versus all chemotherapy-treated patients. RESULTS: From February 2014 to December 2015, 160 patients were screened, 92 were randomized to T + P and 42 to T + P+pac. Baseline characteristics were well balanced (median age 54 versus 51.5 years, cT2 51.1 versus 52.4%, cN0 54.3 versus 61.9%); 91.3% of patients completed T + P per protocol and 92.9% T + P+pac. The pCR rate in the T + P+pac arm was 90.5%, compared with 36.3% in the T + P arm as a whole. In the T + P arm, 24/92 were classified as non-responders, and their pCR rate was only 8.3% compared with 44.7% in responders (38/92) and 42.9% in patients with unclassified early response (30/92). No new safety signals were observed in the study population. CONCLUSION: Addition of taxane monotherapy to dual HER2 blockade in a 12-week neoadjuvant setting substantially increases pCR rates in HER2+/HR- EBC compared with dual blockade alone, even within early responders to dual blockade. Early non-response under dual blockade strongly predicts failure to achieve pCR.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Terapia Neoadyuvante , Receptor ErbB-2/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Pronóstico , Estudios Prospectivos , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Tasa de Supervivencia , Trastuzumab/administración & dosificación , Adulto Joven
11.
Toxicol Appl Pharmacol ; 330: 1-8, 2017 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-28673684

RESUMEN

Non-alcoholic steatohepatitis (NASH) is a form of non-alcoholic fatty liver disease (NAFLD) characterized by steatosis, inflammation, and fibrosis often associated with metabolic syndrome. Fibroblast growth factor 15 (FGF15), an endocrine factor mainly produced in the distal part of small intestine, has emerged to be a critical factor in regulating bile acid homeostasis, energy metabolism, and liver regeneration. We hypothesized that FGF15 alters the development of each of the listed features of NASH. To test this hypothesis, four-week old male Fgf15-/- and their corresponding wild-type (WT) mice were fed either a high fat diet (HFD) or a control chow diet for six months. The results confirmed that HFD feeding for six months in WT mice recapitulated human NASH phenotype, including macrovesicular steatosis, inflammation, and fibrosis. Whereas FGF15 deficiency had no effect on the severity of liver steatosis or inflammation, it was associated with decreased liver fibrosis. Furthermore, FGF15 deficiency resulted in abnormal bile acid homeostasis, increased insulin resistance, increased HFD-induced serum triglycerides, decreased inductions of hepatic cholesterol content by HFD, and altered gene expression of lipid metabolic enzymes. These data suggest that FGF15 improves lipid homeostasis and reduces bile acid synthesis, but promotes fibrosis during the development of NASH.


Asunto(s)
Dieta Alta en Grasa/efectos adversos , Factores de Crecimiento de Fibroblastos/deficiencia , Enfermedad del Hígado Graso no Alcohólico/patología , Animales , Ácidos y Sales Biliares/metabolismo , Colesterol/metabolismo , Hepatitis/patología , Homeostasis/genética , Resistencia a la Insulina , Hígado/metabolismo , Cirrosis Hepática/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Enfermedad del Hígado Graso no Alcohólico/etiología , Triglicéridos/sangre
12.
Appl Opt ; 56(4): C193-C200, 2017 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-28158073

RESUMEN

Random effects in the repeatability of refractive index and absorption edge position of tantalum pentoxide layers prepared by plasma-ion-assisted electron-beam evaporation, ion beam sputtering, and magnetron sputtering are investigated and quantified. Standard deviations in refractive index between 4*10-4 and 4*10-3 have been obtained. Here, lowest standard deviations in refractive index close to our detection threshold could be achieved by both ion beam sputtering and plasma-ion-assisted deposition. In relation to the corresponding mean values, the standard deviations in band-edge position and refractive index are of similar order.

13.
Anaesthesia ; 72(5): 592-597, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28251618

RESUMEN

Recent incidents involving chemical, biological, radiological and nuclear substances have stressed the importance of sufficient personal protection equipment for medical first-responders. Modern lightweight, battery-independent, suit ensembles may prove superior to the current protective suit used in the UK. This study compared the powered respiratory protective suit (PRPS ensemble) with a lightweight suit consisting of a SARATOGA® Multipurpose CBRN Protective Coverall Polyprotect 12 in conjunction with the Avon C50 Respirator/Avon CBRNF12CE filter canister and butyl rubber protective gloves (Polyprotect 12 ensemble). Thirty anaesthetists carried out a standardised resuscitation scenario either unprotected (control) or wearing the PRPS or Polyprotect 12 ensembles in a randomised, crossover simulation study. Treatment times for five simulated advanced life support interventions (application of monitoring; bag/mask ventilation; tracheal intubation; drug and fluid administration; and external pacing) were measured. Wearer comfort was also assessed for the two protective suits by questionnaire. All participants accomplished the treatment objectives of all study arms without adverse events. Total mean (SD) completion time for the five interventions was significantly longer for the PRPS compared with the Polyprotect 12 ensemble (204 (53) s vs. 149 (36) s, respectively; p < 0.0001). Participants rated mobility, noise, heat, vision, dexterity and speech intelligibility significantly better in the Polyprotect 12 ensemble compared with the PRPS ensemble. The combination of a lightweight Polyprotect 12 suit and an Avon C50 air-purifying respirator is preferable to the powered respiratory protective suit during simulated emergency life support, due to a combination of shorter task completion times and improved mobility, communication and dexterity.


Asunto(s)
Apoyo Vital Cardíaco Avanzado , Socorristas , Ropa de Protección , Reanimación Cardiopulmonar , Comunicación , Estudios Cruzados , Diseño de Equipo , Humanos , Dispositivos de Protección Respiratoria , Ventiladores Mecánicos
15.
Dis Esophagus ; 29(8): 1032-1042, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26541887

RESUMEN

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) and anorectal malformations (ARM) represent the severe ends of the fore- and hindgut malformation spectra. Previous research suggests that environmental factors are implicated in their etiology. These risk factors might indicate the influence of specific etiological mechanisms on distinct developmental processes (e.g. fore- vs. hindgut malformation). The present study compared environmental factors in patients with isolated EA/TEF, isolated ARM, and the combined phenotype during the periconceptional period and the first trimester of pregnancy in order to investigate the hypothesis that fore- and hindgut malformations involve differing environmental factors. Patients with isolated EA/TEF (n = 98), isolated ARM (n = 123), and the combined phenotype (n = 42) were included. Families were recruited within the context of two German multicenter studies of the genetic and environmental causes of EA/TEF (great consortium) and ARM (CURE-Net). Exposures of interest were ascertained using an epidemiological questionnaire. Chi-square, Fisher's exact, and Mann-Whitney U-tests were used to assess differences between the three phenotypes. Newborns with isolated EA/TEF and the combined phenotype had significantly lower birth weights than newborns with isolated ARM (P = 0.001 and P < 0.0001, respectively). Mothers of isolated EA/TEF consumed more alcohol periconceptional (80%) than mothers of isolated ARM or the combined phenotype (each 67%). Parental smoking (P = 0.003) and artificial reproductive techniques (P = 0.03) were associated with isolated ARM. Unexpectedly, maternal periconceptional multivitamin supplementation was most frequent among patients with the most severe form of disorder, i.e. the combined phenotype (19%). Significant differences in birth weight were apparent between the three phenotype groups. This might be attributable to the limited ability of EA/TEF fetuses to swallow amniotic fluid, thus depriving them of its nutritive properties. Furthermore, the present data suggest that fore- and hindgut malformations involve differing environmental factors. Maternal periconceptional multivitamin supplementation was highest among patients with the combined phenotype. This latter finding is contrary to expectation, and warrants further analysis in large prospective epidemiological studies.


Asunto(s)
Malformaciones Anorrectales/etiología , Atresia Esofágica/etiología , Fístula Traqueoesofágica/etiología , Adolescente , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Malformaciones Anorrectales/epidemiología , Peso al Nacer , Distribución de Chi-Cuadrado , Niño , Preescolar , Suplementos Dietéticos/efectos adversos , Atresia Esofágica/epidemiología , Femenino , Alemania/epidemiología , Edad Gestacional , Humanos , Lactante , Recién Nacido , Masculino , Madres/estadística & datos numéricos , Fenotipo , Embarazo , Atención Prenatal/estadística & datos numéricos , Efectos Tardíos de la Exposición Prenatal/etiología , Fenómenos Fisiologicos de la Nutrición Prenatal , Técnicas Reproductivas Asistidas/efectos adversos , Factores de Riesgo , Fumar/efectos adversos , Estadísticas no Paramétricas , Fístula Traqueoesofágica/epidemiología , Vitaminas/efectos adversos
16.
Clin Exp Immunol ; 180(1): 90-7, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25382802

RESUMEN

Sepsis and type 2 diabetes exhibit insulin resistance as a common phenotype. In type 2 diabetes we and others have recently provided evidence that alterations of the proinflammatory wingless-related integration site (wnt)-5a/anti-inflammatory secreted frizzled-related protein (sFRP)-5 system are involved in the pathogenesis of insulin resistance. The aim of the present study was to investigate whether this novel cytokine system is dysregulated in human sepsis, which may indicate a potential mechanism linking inflammation to metabolism. In this single-centre prospective observational study, critically ill adult septic patients were examined and proinflammatory wnt5a and wnt5a inhibitor sFRP5 were measured in serum samples by enzyme-linked immunosorbent assay (ELISA) at admission to the intensive care unit (ICU) and 5 days later. Sixty sepsis patients were included, and 30 healthy individuals served as controls. Wnt5a levels were found to be increased significantly in septic patients compared to healthy controls (2·21 ± 0·33 versus 0·32 ± 0·03 ng/ml, P < 0·0001). In contrast, sFRP5 was not altered significantly in septic patients (19·72 ± 3·06 versus 17·48 ± 6·38 ng/ml, P = 0·07). On admission to the ICU, wnt5a levels exhibited a significant positive correlation with the leucocyte count (rs = 0·3797, P = 0·004). Interestingly, in patients recovering from sepsis, wnt5a levels declined significantly within 5 days (2·17 ± 0·38-1·03 ± 0·28 ng/ml, P < 0·01). In contrast, if sepsis was worsening, wnt5a levels increased in the same time-period by trend (2·34 ± 0·59-3·25 ± 1·02 ng/ml, P > 0·05). sFRP5 levels did not change significantly throughout the study period. The wnt5a/sFRP5 system is altered in human sepsis and might therefore be of interest for future studies on molecular pathophysiology of this common human disease.


Asunto(s)
Proteínas del Ojo/sangre , Proteínas de la Membrana/sangre , Proteínas Proto-Oncogénicas/sangre , Sepsis/sangre , Proteínas Wnt/sangre , Proteínas Adaptadoras Transductoras de Señales , Adulto , Anciano , Anciano de 80 o más Años , Ensayo de Inmunoadsorción Enzimática , Proteínas del Ojo/inmunología , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Proteínas de la Membrana/inmunología , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Proto-Oncogénicas/inmunología , Sepsis/inmunología , Factores de Tiempo , Proteínas Wnt/inmunología , Proteína Wnt-5a
18.
Contrib Mineral Petrol ; 168(1): 1038, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-26069344

RESUMEN

Kimberlite volcanism involves the emplacement of olivine-rich volcaniclastic deposits into volcanic vents or pipes. Kimberlite deposits are typically pervasively serpentinised as a result of the reaction of olivine and water within a temperature range of 130-400 °C or less. We present a model for the influx of ground water into hot kimberlite deposits coupled with progressive cooling and serpentisation. Large-pressure gradients cause influx and heating of water within the pipe with horizontal convergent flow in the host rock and along pipe margins, and upward flow within the pipe centre. Complete serpentisation is predicted for wide ranges of permeability of the host rocks and kimberlite deposits. For typical pipe dimensions, cooling times are centuries to a few millennia. Excess volume of serpentine results in filling of pore spaces, eventually inhibiting fluid flow. Fresh olivine is preserved in lithofacies with initial low porosity, and at the base of the pipe where deeper-level host rocks have low permeability, and the pipe is narrower leading to faster cooling. These predictions are consistent with fresh olivine and serpentine distribution in the Diavik A418 kimberlite pipe, (NWT, Canada) and with features of kimberlites of the Yakutian province in Russia affected by influx of ground water brines. Fast reactions and increases in the volume of solid products compared to the reactants result in self-sealing and low water-rock ratios (estimated at <0.2). Such low water-rock ratios result in only small changes in stable isotope compositions; for example, δO18 is predicted only to change slightly from mantle values. The model supports alteration of kimberlites predominantly by interactions with external non-magmatic fluids.

19.
Z Gerontol Geriatr ; 47(2): 141-6, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23743881

RESUMEN

BACKGROUND: Single or frequent falls lead to increased morbidity due to fall-related injury, fear of falling, impairments in quality of life and loss of independence. To assess the impact of falls, prevalence data are essential. METHODS: In 2006, a telephone survey was performed in a random sample of 1270 inhabitants of the city of Herne, Germany, aged 40 years or older. Participants were asked about falls during the previous 4 weeks and 6 and 12 months, respectively. A fall was defined as an unexpected event in which the individual comes to rest on the ground, floor or a lower level. Participants were also asked about pain and whether or not a medical diagnosis of osteoporosis had ever been made. Standardized prevalences and odds ratios (OR) with 95 % confidence interval are reported. RESULTS: In total, 862 (67.9 %) adults participated. Participants were significantly older than non-participants and more often female than male. Prevalences standardized for the population of Herne for at least one fall within the previous 4 weeks or 12 months or two or more falls within 12 months, respectively, were 3.1 %, 12.1 %, and 4.5 %. Women were more often affected than men. A total of 2.3 % participants reported both at least one fall and a medical diagnosis of osteoporosis. The prevalence of falls increased with increasing age and was also related to musculoskeletal pain. CONCLUSIONS: Our estimates indicate that single and multiple falls affect a substantial proportion of adults in the urban population. Risk groups such as older adults and females with osteoporosis might represent a target group when considering measures for fall prevention.


Asunto(s)
Accidentes por Caídas/estadística & datos numéricos , Dolor Musculoesquelético/epidemiología , Osteoporosis/epidemiología , Población Urbana/estadística & datos numéricos , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Causalidad , Comorbilidad , Femenino , Alemania/epidemiología , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Prevalencia , Medición de Riesgo , Distribución por Sexo
20.
New Phytol ; 197(1): 238-250, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23057437

RESUMEN

A large database of invasive forest pathogens (IFPs) was developed to investigate the patterns and determinants of invasion in Europe. Detailed taxonomic and biological information on the invasive species was combined with country-specific data on land use, climate, and the time since invasion to identify the determinants of invasiveness, and to differentiate the class of environments which share territorial and climate features associated with a susceptibility to invasion. IFPs increased exponentially in the last four decades. Until 1919, IFPs already present moved across Europe. Then, new IFPs were introduced mainly from North America, and recently from Asia. Hybrid pathogens also appeared. Countries with a wider range of environments, higher human impact or international trade hosted more IFPs. Rainfall influenced the diffusion rates. Environmental conditions of the new and original ranges and systematic and ecological attributes affected invasiveness. Further spread of established IFPs is expected in countries that have experienced commercial isolation in the recent past. Densely populated countries with high environmental diversity may be the weakest links in attempts to prevent new arrivals. Tight coordination of actions against new arrivals is needed. Eradication seems impossible, and prevention seems the only reliable measure, although this will be difficult in the face of global mobility.


Asunto(s)
Bases de Datos Factuales , Hongos/patogenicidad , Especies Introducidas , Árboles/microbiología , Clima , Ecosistema , Europa (Continente) , Hongos/clasificación , Hongos/fisiología , Geografía , Modelos Lineales , Enfermedades de las Plantas/microbiología , Densidad de Población , Análisis de Componente Principal , Lluvia , Factores Socioeconómicos , Temperatura , Factores de Tiempo , Árboles/fisiología
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