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Since December 2019 a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has rapidly spread around the world resulting in an acute respiratory illness pandemic. The immense challenges for clinicians and hospitals as well as the strain on many healthcare systems has been unprecedented.The majority of patients present with mild symptoms of coronavirus disease 2019 (COVID-19); however, 5-8% become critically ill and require intensive care treatment. Acute hypoxemic respiratory failure with severe dyspnea and an increased respiratory rate (>30/min) usually leads to intensive care unit (ICU) admission. At this point bilateral pulmonary infiltrates are typically seen. Patients often develop a severe acute respiratory distress syndrome (ARDS).So far, remdesivir and dexamethasone have shown clinical effectiveness in severe COVID-19 in hospitalized patients. The main goal of supportive treatment is to ascertain adequate oxygenation. Invasive mechanical ventilation and repeated prone positioning are key elements in treating severely hypoxemic COVID-19 patients.Strict adherence to basic infection control measures (including hand hygiene) and correct use of personal protection equipment (PPE) are essential in the care of patients. Procedures that lead to formation of aerosols should be carried out with utmost precaution and preparation.
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COVID-19 , Enfermedad Crítica , Humanos , SARS-CoV-2RESUMEN
The COVID-19 pandemic represents a huge burden on global health systems. Although far-reaching prevention measures such as the increase of intensive care capacities and drastic restrictions of public life have so far been able to avert an overload of the German health care system, the current situation implies an exceptionally high burden on medical professionals. The current study presents the results of an opinion evaluation among 513 pneumology specialists in Germany in the period from March 27th to April 11th, 2020. While the majority of respondents stated that Germany was "well" prepared for the pandemic, this assessment was significantly worse among participants from the outpatient sector compared to the hospital sector (pâ<â0.001). Furthermore, a lack of medical protective equipment was reported significantly more frequently by respondents from the outpatient sector (pâ<â0.001). The importance of telemedicine approaches during the COVID-19 pandemic was rated "high" (35.2â%) or "very high" (17.2â%) by most pneumology professionals, with participants from the hospital sector giving a higher rating (pâ<â0.001). Finally, 45.8â% of the respondents expressed a "negative" influence of the COVID-19 pandemic on their personal mood and 58.3â% expressed "strong" or "very strong" concerns about the health of their fellow human beings. This assessment was significantly stronger among female participants and participants from the nursing sector (pâ<â0.001). In summary, the current study analyses for the first time the professional and personal impact of the COVID-19 pandemic on pneumology professionals in Germany. The results could help to identify first starting points to better support health professionals during the current and future challenges.
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COVID-19 , Neumología , Femenino , Alemania/epidemiología , Humanos , Pandemias/prevención & control , Percepción , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
Since December 2019, the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - Corona Virus-2) has been spreading rapidly in the sense of a global pandemic. This poses significant challenges for clinicians and hospitals and is placing unprecedented strain on the healthcare systems of many countries. The majority of patients with Coronavirus Disease 2019 (COVID-19) present with only mild symptoms such as cough and fever. However, about 6â% require hospitalization. Early clarification of whether inpatient and, if necessary, intensive care treatment is medically appropriate and desired by the patient is of particular importance in the pandemic. Acute hypoxemic respiratory insufficiency with dyspnea and high respiratory rate (>â30/min) usually leads to admission to the intensive care unit. Often, bilateral pulmonary infiltrates/consolidations or even pulmonary emboli are already found on imaging. As the disease progresses, some of these patients develop acute respiratory distress syndrome (ARDS). Mortality reduction of available drug therapy in severe COVID-19 disease has only been demonstrated for dexamethasone in randomized controlled trials. The main goal of supportive therapy is to ensure adequate oxygenation. In this regard, invasive ventilation and repeated prone positioning are important elements in the treatment of severely hypoxemic COVID-19 patients. Strict adherence to basic hygiene, including hand hygiene, and the correct wearing of adequate personal protective equipment are essential when handling patients. Medically necessary actions on patients that could result in aerosol formation should be performed with extreme care and preparation.
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COVID-19 , Síndrome de Dificultad Respiratoria , Humanos , Pacientes Internos , Pandemias , Guías de Práctica Clínica como Asunto , SARS-CoV-2RESUMEN
BACKGROUND: Patients with oesophageal/gastro-oesophageal junction adenocarcinoma (EAC) not showing early metabolic response (EMR) to chemotherapy have poorer survival and histological response rates <5%. We investigated whether tailoring neoadjuvant therapy can improve outcomes in these patients. PATIENTS AND METHODS: Patients with resectable EAC were enrolled and randomised into two single-arm, multicentre phase II trials. After induction cisplatin and 5-fluorouracil (CF), all were assessed by day 15 positron emission tomography (PET). Patients with an EMR [maximum standardised uptake values (SUVmax) ≥35% reduction from baseline to day 15 PET] received a second CF cycle then oesophagectomy. Non-responders were randomised 1 : 1 to two cycles of CF and docetaxel (DCF, n = 31) or DCF + 45 Gy radiotherapy (DCFRT, n = 35) then oesophagectomy. The primary end point was major histological response (<10% residual tumour) in the oesophagectomy specimen; secondary end points were overall survival (OS), progression-free survival (PFS), and locoregional recurrence (LR). RESULTS: Of 124 patients recruited, major histological response was achieved in 3/45 (7%) with EMR, 6/30 (20%) DCF, and 22/35 (63%) DCFRT patients. Grade 3/4 toxicities occurred in 12/45 (27%) EMR (CF), 13/31 (42%) DCF, and 25/35 (71%) DCFRT patients. No treatment-related deaths occurred. LR by 3 years was seen in 5/45 (11%) EMR, 10/31 (32%) DCF, and 4/35 (11%) DCFRT patients. PFS [95% confidence interval (CI)] at 36 months was 47% (31% to 61%) for EMR, 29% (15% to 45%) for DCF, and 46% (29% to 61%) for DCFRT patients. OS (95% CI) at 60 months was 53% (37% to 67%) for EMR, 31% (16% to 48%) for DCF, and 46% (29% to 61%) for DCFRT patients. CONCLUSIONS: EMR is associated with favourable OS, PFS, and low LR. For non-responders, the addition of docetaxel augmented histological response rates, but OS, PFS, and LR remained inferior compared with responders. DCFRT improved histological response and PFS/LR outcomes, matching the EMR group. Early PET/CT has the potential to tailor therapy for patients not showing an early response to chemotherapy. TRIAL REGISTRATION: ACTRN12609000665235.
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Adenocarcinoma , Neoplasias Esofágicas , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/uso terapéutico , Docetaxel/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Humanos , Recurrencia Local de Neoplasia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Resultado del TratamientoRESUMEN
BACKGROUND: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for extended adjuvant treatment in early-stage HER2-positive breast cancer based on the phase III ExteNET study. In that trial, in which no antidiarrheal prophylaxis was mandated, grade 3 diarrhea was observed in 40% of patients and 17% discontinued due to diarrhea. The international, open-label, sequential-cohort, phase II CONTROL study is investigating several strategies to improve tolerability. PATIENTS AND METHODS: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year plus loperamide prophylaxis (days 1-28 or 1-56). Sequential cohorts evaluated additional budesonide or colestipol prophylaxis (days 1-28) and neratinib dose escalation (DE; ongoing). The primary end point was the incidence of grade ≥3 diarrhea. RESULTS: Final data for loperamide (L; n = 137), budesonide + loperamide (BL; n = 64), colestipol + loperamide (CL; n = 136), and colestipol + as-needed loperamide (CL-PRN; n = 104) cohorts, and interim data for DE (n = 60; completed ≥six cycles or discontinued; median duration 11 months) are available. No grade 4 diarrhea was observed. Grade 3 diarrhea rates were lower than ExteNET in all cohorts and lowest in DE (L 31%, BL 28%, CL 21%, CL-PRN 32%, DE 15%). Median number of grade 3 diarrhea episodes was one; median duration per grade 3 episode was 1.0-2.0 days across cohorts. Most grade 3 diarrhea and diarrhea-related discontinuations occurred in month 1. Diarrhea-related discontinuations were lowest in DE (L 20%, BL 8%, CL 4%, CL-PRN 8%, DE 3%). Decreases in health-related quality of life did not cross the clinically important threshold. CONCLUSIONS: Neratinib tolerability was improved with preemptive prophylaxis or DE, which reduced the rate, severity, and duration of neratinib-associated grade ≥3 diarrhea compared with ExteNET. Lower diarrhea-related treatment discontinuations in multiple cohorts indicate that proactive management can allow patients to stay on neratinib for the recommended time period. CLINICALTRIALS.GOV: NCT02400476.
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Neoplasias de la Mama , Quinolinas , Receptor ErbB-2 , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Humanos , Calidad de Vida , Quinolinas/uso terapéutico , Receptor ErbB-2/genética , Trastuzumab/uso terapéuticoRESUMEN
Size-selected dianionic lead clusters Pb_{n}^{2-}, n=34-56, are stored in a Penning trap and studied with respect to their decay products upon photoexcitation. Contrary to the decay of other dianionic metal clusters, these lead clusters show a variety of decay channels. The mass spectra of the fragments are compared to the corresponding spectra of the monoanionic precursors. This comparison leads to the conclusion that, in the cluster size region below about n=48, the fission reaction Pb_{n}^{2-}âPb_{n-10}^{-}+Pb_{10}^{-} is the major decay process. Its disappearance at larger cluster sizes may be an indication of a nonmetal to metal transition. Recently, the pair of Pb_{10}^{-} and Pb_{n-10}^{-} were observed as pronounced fragments in electron-attachment studies [S. König et al., Int. J. Mass Spectrom. 421, 129 (2017)IMSPF81387-380610.1016/j.ijms.2017.06.009]. The present findings suggest that this combination is the fingerprint of the decay of doubly charged lead clusters. With this assumption, the dianion clusters have been traced down to Pb_{21}^{2-}, whereas the smallest size for the direct observation was as high as n=28.
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BACKGROUND: For cardiac surgery patients who were employed prior to surgery, the return to their professional life is of special importance. In addition to medical reasons, such as pre-existing conditions, the success of the operation or postoperative course and patient-intrinsic reasons, which can be assessed with the Sense of Coherence (SOC) scale by Antonovsky, may also play a role in the question of a possible return into working life. METHODS: In this study 278 patients (invasive coronary artery bypass graft surgery and/or surgery on heart valves, ageâ¯< 60 years, employed) were questioned postoperatively via post with the SOC questionnaire. The SOC questionnaire was used in addition to questions about return to work. The cohort was stratified according to the time of return to work. Subsequently, the point of maximum sensitivity and specificity was determined for the total SOC score and the prediction power was considered. RESULTS: Of the 278 patients, 61 questionnaires (22%) were considered as eligible and included in the analysis. Of these, 47 participants had returned to work after undergoing cardiac surgery and 14 participants had not. We observed significant differences in SOC values between both groups (146.07⯱ 29.76 versus 124.29⯱ 28.8, pâ¯= 0.020). Patients that returned to work within the first 6 months after surgery showed even higher SOC scores (148.56⯱ 28.98, pâ¯= 0.034). CONCLUSION: Patients with an SOC scoreâ¯< 130 are at greater risk not to return to their professional life after cardiac surgery. The SOC is an easily obtainable score that reliably predicts the probability of return to work after cardiac surgery.
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Sentido de Coherencia/fisiología , Cirugía Torácica , Adulto , Anciano , Cuidados Críticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Calidad de Vida , Reinserción al Trabajo , Encuestas y CuestionariosRESUMEN
INTRODUCTION: High-titre factor VIII (FVIII) inhibitors complicate peri-operative haemostasis. Recombinant porcine FVIII (r-pFVIII) may provide an alternative haemostatic agent for high-risk procedures and allow FVIII activity monitoring. AIM: Devise an effective haemostatic plan for repair of a progressively symptomatic aortic coarctation in a 5-year-old male with immune tolerance induction (ITI) refractory high-titre FVIII inhibitors. METHODS: Preprocedure human FVIII inhibitor titre was 58 Bethesda Units mL-1 (BU) and cross-reacted to neutralize porcine FVIII at 30 BU. Daily ITI with plasma-derived FVIII concentrate was supplemented with anti-B-cell and anti-plasma cell immunotherapy to reduce FVIII inhibitor titres. Potential haemostatic agents were evaluated in comparative ex vivo thrombin generation assays (TGA). RESULTS: Four weeks after immunosuppression, human and porcine inhibitor titres declined to 16 and 2 BU respectively. TGA with r-pFVIII was less robust than with activated prothrombin complex concentrate (aPCC); however, r-pFVIII was selected for cardiac surgery to secure the ability to assay FVIII levels throughout this high-bleeding risk procedure. Haemostasis with r-pFVIII was excellent; initial trough FVIII activity levels ranged from 0.81-1.17 IU mL-1 . On postoperative day 3, peak and trough levels markedly declined suggesting a rising porcine inhibitor titre. Postprocedure prophylaxis was transitioned to aPCC, informed by TGA. CONCLUSIONS: R-pFVIII provided effective peri-procedural haemostasis with no adverse events. Rapid neutralization of r-pFVIII after the first 60 hours, despite intensive immune suppression, accentuates the importance of careful monitoring. Use of TGA can support bypassing agent selection for convalescence. The comparative cost of r-pFVIII may limit its use to high morbidity clinical scenarios.
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Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , Animales , Preescolar , Humanos , Masculino , Proteínas Recombinantes/administración & dosificación , PorcinosRESUMEN
PURPOSE: Fatigue is a prevalent and debilitating side effect of docetaxel chemotherapy in metastatic prostate cancer. A better understanding of the kinetics and nature of docetaxel-related fatigue may provide a framework for intervention. METHODS: This secondary analysis was performed using the MOTIF database, from a phase III, randomised, double-blind, placebo-controlled study of modafinil (200 mg/day for 15 days) for docetaxel-related fatigue in men with metastatic prostate cancer [1]. The pattern of fatigue was analysed using the MDASI (MD Anderson Symptom Inventory) score. The impact of modafinil, cumulative docetaxel exposure, age and smoking status on fatigue kinetics were explored. Fatigue-related symptoms were assessed using the SOMA6 (fatigue and related symptoms) subset of the SPHERE (Somatic and Psychological Health Report). Mood was tracked using the short form 36 health survey questionnaire (SF-36). RESULTS: Across four docetaxel cycles, fatigue scores were higher in the first week and decreased over weeks two and three. Whilst men randomised to modafinil had reduced fatigue scores, cumulative docetaxel had little impact. Younger men (55-68 years) had significantly reduced fatigue scores, whereas current and ex-smokers had higher scores. There was no significant change in mood status or haemoglobin across treatment cycles. Men described both 'somnolence' and 'muscle fatigue' contributing significantly to their symptom complex. CONCLUSIONS: Assessment and management of docetaxel-related fatigue remains an important challenge. Given the complex, multifactorial nature of fatigue, identification through structured interview and interventions targeted to specific 'at risk' groups may be the most beneficial. Understanding the temporal pattern (kinetics) and nature of fatigue is critical to guide this process.
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Compuestos de Bencidrilo/efectos adversos , Fatiga/inducido químicamente , Neoplasias de la Próstata/complicaciones , Taxoides/uso terapéutico , Anciano , Anciano de 80 o más Años , Docetaxel , Método Doble Ciego , Humanos , Masculino , Persona de Mediana Edad , Modafinilo , Metástasis de la Neoplasia , Neoplasias de la Próstata/tratamiento farmacológico , Encuestas y Cuestionarios , Taxoides/administración & dosificación , Taxoides/farmacologíaRESUMEN
Recent ab initio folding simulations for a limited number of small proteins have corroborated a previous suggestion that atomic burial information obtainable from sequence could be sufficient for tertiary structure determination when combined to sequence-independent geometrical constraints. Here, we use simulations parameterized by native burials to investigate the required amount of information in a diverse set of globular proteins comprising different structural classes and a wide size range. Burial information is provided by a potential term pushing each atom towards one among a small number L of equiprobable concentric layers. An upper bound for the required information is provided by the minimal number of layers L(min) still compatible with correct folding behavior. We obtain L(min) between 3 and 5 for seven small to medium proteins with 50 ≤ Nr ≤ 110 residues while for a larger protein with Nr = 141 we find that L ≥ 6 is required to maintain native stability. We additionally estimate the usable redundancy for a given L ≥ L(min) from the burial entropy associated to the largest folding-compatible fraction of "superfluous" atoms, for which the burial term can be turned off or target layers can be chosen randomly. The estimated redundancy for small proteins with L = 4 is close to 0.8. Our results are consistent with the above-average quality of burial predictions used in previous simulations and indicate that the fraction of approachable proteins could increase significantly with even a mild, plausible, improvement on sequence-dependent burial prediction or on sequence-independent constraints that augment the detectable redundancy during simulations.
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Algoritmos , Modelos Moleculares , Proteínas/química , Secuencia de Aminoácidos , Simulación por Computador , Método de Montecarlo , Pliegue de Proteína , Estructura Terciaria de Proteína , TermodinámicaRESUMEN
The mass of an atom incorporates all its constituents and their interactions. The difference between the mass of an atom and the sum of its building blocks (the binding energy) is a manifestation of Einstein's famous relation E = mc(2). The binding energy determines the energy available for nuclear reactions and decays (and thus the creation of elements by stellar nucleosynthesis), and holds the key to the fundamental question of how heavy the elements can be. Superheavy elements have been observed in challenging production experiments, but our present knowledge of the binding energy of these nuclides is based only on the detection of their decay products. The reconstruction from extended decay chains introduces uncertainties that render the interpretation difficult. Here we report direct mass measurements of trans-uranium nuclides. Located at the farthest tip of the actinide species on the proton number-neutron number diagram, these nuclides represent the gateway to the predicted island of stability. In particular, we have determined the mass values of (252-254)No (atomic number 102) with the Penning trap mass spectrometer SHIPTRAP. The uncertainties are of the order of 10 keV/c(2) (representing a relative precision of 0.05 p.p.m.), despite minute production rates of less than one atom per second. Our experiments advance direct mass measurements by ten atomic numbers with no loss in accuracy, and provide reliable anchor points en route to the island of stability.
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BACKGROUND: It is not clear whether patients entering a specialized, interdisciplinary weaning unit from surgical or medical intensive care units (ICU) distinguish substantially. The purpose of the present study was to assess differences in patients with prolonged weaning being referred from surgical and medical ICU. METHODS: Data collected from April 2013 to April 2014 was conducted for retrospective analysis. Mortality rates, demographic data, clinical, and microbial differences in 150 patients with prolonged weaning were assessed (80 surgical and 70 medical). RESULTS: Surgical ICU referrals tended to be older (70.7 ± 11.3 vs. 67.3 ± 12.3, P = 0.051) and had fewer underlying pulmonary diseases (45% vs. 60%, P = 0.067). Sodium values at the time of referral to the weaning unit were significantly higher in surgical (147.1 ± 9.6) vs. medical (141.3 ± 6.7 mmol/l) patients (P < 0.001). Each 10-unit increase in sodium at the time of referral to the weaning unit was associated with a 2.5-day (95% CI -0.4, 5.4; P = 0.09) prolongation of stay in the weaning unit. Although significant differences in microbiological agents from tracheal aspiration were seen, the infection rate on the weaning unit was similar in both groups. There was no difference in weaning unit mortality between surgical and medical ICU patients (18% vs. 23%; P = 0.41). CONCLUSION: Few differences were found between patients being referred to a specialized weaning unit from surgical vs. medical ICUs. Besides differences in microbiological characteristics of tracheal secretions, there were also differences in sodium levels, which appear to influence on treatment duration.
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Unidades de Cuidados Intensivos , Desconexión del Ventilador , Anciano , Anciano de 80 o más Años , Farmacorresistencia Bacteriana , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Neumonía Asociada al Ventilador/etiología , Derivación y Consulta , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: Docetaxel improves symptoms and survival in metastatic castration-resistant prostate cancer (CRPC). However, â¼50% of patients are chemoresistant. This study examined whether changes in cytokine levels predict for docetaxel resistance in vitro and in a clinical cohort. METHODS: PC3 cells or their docetaxel-resistant subline (PC3Rx) were co-cultured with U937 monocytes, with and without docetaxel treatment, and cytokine levels were measured. The circulating levels of 28 cytokines were measured pre-/post cycle 1 of docetaxel from 55 men with CRPC, and compared with prostate-specific antigen (PSA) response. RESULTS: PC3Rx-U937 co-culture expressed more cytokines, chiefly markers of alternative macrophage differentiation, compared with PC3-U937 co-culture. Docetaxel treatment enhanced cytokine production by PC3Rx-U937 co-culture, while reducing cytokine levels in PC3-U937. In patients, changes in the levels of seven circulating cytokines (macrophage inhibitory cytokine 1 (MIC1), interleukin (IL)-1ra, IL-1ß, IL-4, IL-6, IL-12 and IFNγ) after cycle 1 of docetaxel were associated with progressive disease (all P<0.05). The combination of changes in MIC1, IL-4 and IL-6 most strongly predicted PSA response (P=0.002). CONCLUSIONS: In vitro studies suggest docetaxel resistance is mediated, at least in part, by cytokines induced by the interaction between the docetaxel-resistant tumour cells and macrophages. Early changes in circulating cytokine levels were associated with docetaxel resistance in CRPC patients. When considered together, these data suggest a significant role for the inflammatory response and macrophages in the development of docetaxel resistance in CRPC.
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Citocinas/sangre , Resistencia a Antineoplásicos , Calicreínas/sangre , Macrófagos/metabolismo , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Línea Celular Tumoral , Técnicas de Cocultivo , Docetaxel , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Taxoides/farmacologíaRESUMEN
This manuscript is a very general and non-political review on major issues concerning the evolving structural and organizational aspects of intensive care medicine, which may influence the outcomes of patients. It merely raises a multitude of issues, which deserve discussion in the different contexts of countries or communities.
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Cuidados Críticos , Humanos , Derivación y Consulta , TelemedicinaRESUMEN
BACKGROUND: Glutathione S-transferase 1 (GSTP1) inactivation is associated with CpG island promoter hypermethylation in the majority of prostate cancers (PCs). This study assessed whether the level of circulating methylated GSTP1 (mGSTP1) in plasma DNA is associated with chemotherapy response and overall survival (OS). METHODS: Plasma samples were collected prospectively from a Phase I exploratory cohort of 75 men with castrate-resistant PC (CRPC) and a Phase II independent validation cohort (n=51). mGSTP1 levels in free DNA were measured using a sensitive methylation-specific PCR assay. RESULTS: The Phase I cohort identified that detectable baseline mGSTP1 DNA was associated with poorer OS (HR, 4.2 95% CI 2.1-8.2; P<0.0001). A decrease in mGSTP1 DNA levels after cycle 1 was associated with a PSA response (P=0.008). In the Phase II cohort, baseline mGSTP1 DNA was a stronger predictor of OS than PSA change after 3 months (P=0.02). Undetectable plasma mGSTP1 after one cycle of chemotherapy was associated with PSA response (P=0.007). CONCLUSIONS: We identified plasma mGSTP1 DNA as a potential prognostic marker in men with CRPC as well as a potential surrogate therapeutic efficacy marker for chemotherapy and corroborated these findings in an independent Phase II cohort. Prospective Phase III assessment of mGSTP1 levels in plasma DNA is now warranted.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Metilación de ADN , ADN de Neoplasias/genética , Epigenómica , Gutatión-S-Transferasa pi/genética , Neoplasias de la Próstata Resistentes a la Castración/genética , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Islas de CpG , ADN de Neoplasias/sangre , Estudios de Seguimiento , Gutatión-S-Transferasa pi/sangre , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Células Neoplásicas Circulantes/efectos de los fármacos , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Reacción en Cadena de la Polimerasa , Pronóstico , Regiones Promotoras Genéticas/genética , Estudios Prospectivos , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Tasa de Supervivencia , Estudios de Validación como AsuntoRESUMEN
BACKGROUND: Docetaxel is the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, response rates are â¼50% and determined quite late in the treatment schedule, thus non-responders are subjected to unnecessary toxicity. The potential of circulating microRNAs as early biomarkers of docetaxel response in CRPC patients was investigated in this study. METHODS: Global microRNA profiling was performed on docetaxel-resistant and sensitive cell lines to identify candidate circulating microRNA biomarkers. Custom Taqman Array MicroRNA cards were used to measure the levels of 46 candidate microRNAs in plasma/serum samples, collected before and after docetaxel treatment, from 97 CRPC patients. RESULTS: Fourteen microRNAs were associated with serum prostate-specific antigen (PSA) response or overall survival, according to Mann-Whitney U or log-rank tests. Non-responders to docetaxel and patients with shorter survival generally had high pre-docetaxel levels of miR-200 family members or decreased/unchanged post-docetaxel levels of miR-17 family members. Multivariate Cox regression with bootstrapping validation showed that pre-docetaxel miR-200b levels, post-docetaxel change in miR-20a levels, pre-docetaxel haemoglobin levels and visceral metastasis were independent predictors of overall survival when modelled together. CONCLUSIONS: Our study suggests that circulating microRNAs are potential early predictors of docetaxel chemotherapy outcome, and warrant further investigation in clinical trials.
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Adenocarcinoma/tratamiento farmacológico , Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Biomarcadores de Tumor/sangre , Resistencia a Antineoplásicos/genética , MicroARNs/sangre , Neoplasias de la Próstata/tratamiento farmacológico , ARN Neoplásico/sangre , Taxoides/uso terapéutico , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Anciano , Anciano de 80 o más Años , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral/efectos de los fármacos , Docetaxel , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Curva ROC , Factores de Riesgo , Taxoides/farmacología , Resultado del TratamientoRESUMEN
The purpose of this report was to assess the safety and application of chlorhexidine (CHG)-containing dressings--shown to reduce central line infection rates markedly--for external ventricular drainages (EVDs) and lumbar drainages (LDs). Cerebrospinal fluid samples of patients receiving standard dressings and CHG-containing dressing (ten each) were analyzed by high-performance liquid chromatography for the presence of CHG. The application was evaluated. CHG was not detectable in all samples. The dressings' application for EVDs and LDs worked without problems. Thus, the use of CHG-containing dressings for EVDs and LDs seems to be safe. Further studies addressing their infection reduction potential are warranted.
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Antiinfecciosos Locales/uso terapéutico , Infecciones Bacterianas/prevención & control , Vendajes/efectos adversos , Derivaciones del Líquido Cefalorraquídeo/efectos adversos , Clorhexidina/uso terapéutico , Control de Infecciones/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antiinfecciosos Locales/efectos adversos , Antiinfecciosos Locales/análisis , Líquido Cefalorraquídeo/química , Clorhexidina/efectos adversos , Clorhexidina/análisis , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Adulto JovenRESUMEN
Competitive bodybuilding is a weightlifting sport similar to powerlifting, strongman competition and Olympic weightlifting, which aims to increase muscle mass, symmetry, and body definition. Although data regarding rates of injury, overuse syndromes and pain during routine training is available for these other disciplines, it is rare for competitive bodybuilding. The aim of this study was to investigate rates of injury, pain during workouts and/or overuse syndromes, as well as the influence of particular intrinsic and external factors. Data was collected using questionnaires from 71 competitive and elite bodybuilders. The information included training routines and prior injuries. Participants were recruited from bodybuilding clubs in Germany. 45.1% of athletes reported symptoms while training. The overall injury rate was computed to be 0.12 injuries per bodybuilder per year (0.24 injuries per 1 000 h of bodybuilding). Athletes over 40 exhibited higher rates of injury (p=0.029). Other investigated parameters showed no effects. Most injuries occurred in the shoulder, elbow, lumbar spine and knee regions. A large proportion of bodybuilders complained of pain not resulting in interruptions of training/competition. The injury rate is low compared to other weightlifting disciplines such as powerlifting, Olympic weightlifting or strongman competition. In comparison to team or contact sports the injury rate is minimal.
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Trastornos de Traumas Acumulados/epidemiología , Levantamiento de Peso/lesiones , Adolescente , Adulto , Conducta Competitiva/fisiología , Femenino , Alemania/epidemiología , Humanos , Extremidad Inferior/lesiones , Masculino , Persona de Mediana Edad , Dolor/epidemiología , Entrenamiento de Fuerza/efectos adversos , Estudios Retrospectivos , Traumatismos Vertebrales/epidemiología , Extremidad Superior/lesiones , Adulto JovenRESUMEN
PURPOSE: Noninvasive pressure support ventilation is intended to relieve the load on respiratory muscles and to prevent exhaustion. This includes continuous positive airway pressure (CPAP) as well as pressure support ventilation (PSV). Speckle tracking echocardiography (STE) allows quantification of tissue deformation by tracing characteristic grayscale patterns, independent of the acquisition angle. The aim of the present study was to assess the applicability of using STE as a way to investigate diaphragm movement using deformation analysis as a parameter for respiratory workload. MATERIALS AND METHODS: Healthy male subjects (nâ=â13, 27â±â7 years) were treated while in a seated supine position with the following respirator settings: regular breathing, 5 mbar CPAP, CPAP +â5 / +â10 / +â15 mbar PSV. A 2â-â4 MhZ M5S phased array sector transducer was used on a Vivid E 9 (GE, Horton, Norway) to visualize the diaphragm. The inspiratory peak transverse strain was measured as a parameter of maximal inspiratory muscle workload and compared to the M-mode-based fractional thickening (FT). RESULTS: Both the FT and the transverse strain increased significantly under CPAP and PSV. The transverse strain correlated well with the FT (râ=â0.753; pâ<â0.001). CONCLUSION: The results measured by STE were comparable to the M-mode-based measurements. The capturing of a larger diaphragmatic sample area and movement tracking possibly lead to higher precision compared to one-dimensional M-mode. The use of STE in patients might provide a reproducible, bedside method to analyze the respiratory workload. Due to the larger sampling area, it might prove superior to mere M-mode acquisition.