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Background: Anthracyclines are associated with cardiac dysfunction. Little is known about the interplay of pre-existing hypertension and treatment response. We aimed to investigate the relationship between hypertension and the development of cancer therapy-related cardiac dysfunction (CTRCD) in pediatric patients treated with anthracycline chemotherapy. Methods: Pediatric patients with cancer who received anthracycline chemotherapy from 2013 to 2021 were retrospectively included. Serial cardiac assessments were conducted during and after chemotherapy. The primary outcome was the development of CTRCD, classified as mild, moderate, or severe according to contemporary definitions. Results: Among 190 patients undergoing anthracycline chemotherapy, 34 patients (17.9 %) had hypertension (24 patients Stage 1, and 10 patients Stage 2) at baseline evaluation. Patients underwent chemotherapy for a median of 234.4 days (interquartile range 127.8-690.3 days) and were subsequently followed up. Hypertension was frequent during follow-up 31.3 % (0-3 months), 15.8 % (3-6 months), 21.9 % (0.5-1 years), 24.7 % (1-2 years), 31.1 % (2-4 years) and 35.8 % (beyond 4 years) (P for trend < 0.001). Freedom from mild CTRCD at 5 years was 45.0 %, freedom from moderate CTRCD was 87.8 % at 5 years. Baseline hypertension did not increase the risk of mild (HR 0.77, 95 % CI: 0.41-1.42, P = 0.385) or moderate CTRCD (HR 0.62, 95 % CI: 0.14-2.72, P = 0.504). Patients with baseline hypertension showed different global longitudinal strain (P < 0.001) and LVEF (P < 0.001) patterns during follow-up. Conclusions: Pediatric patients often develop CTRCD post-anthracycline chemotherapy. Those with pre-existing hypertension show a unique treatment response, despite no increased CTRCD risk, warranting further investigation.
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Echocardiography is pivotal for diagnosis and monitoring of hypertrophic cardiomyopathy (HCM) and can evaluate myocardial function using myocardial work (MW) calculations. Echocardiography is often supplemented by cardiovascular magnetic resonance (CMR) imaging, which can detect myocardial fibrosis using late gadolinium enhancement (LGE). We sought to study the relationship between baseline LGE and MW at baseline and during follow-up in pediatric HCM patients. During the study period (2008-2023), 75 patients were followed up for HCM. In 14 patients (age 14.2 ± 2.8 years, 50.0% male, 6.4 ± 2.9 years follow-up), both LGE-CMR and echocardiography were performed. Global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency (GWE) were measured, and myocardial fibrosis was estimated by qualitative assessment of LGE. Patients with LGE (n = 7) exhibited significantly impaired baseline MW, including GWI (mean difference, MD - 487.4 mmHg %, 95% CI [- 866.8 mmHg % to - 108.3 mmHg %], p = 0.027), GCW (MD - 536.8 mmHg %, 95% CI [- 929.8 mmHg % to - 144.4 mmHg %], p = 0.020), and GWE (MD - 4.4%, 95% CI [- 8.1% to - 0.7%], p = 0.039). Regional analysis revealed impaired MW indices in segments with LGE, notably basal and mid septal segments. GWI demonstrated high diagnostic performance for LGE presence (sensitivity 93%, specificity 88%, and area under receiver operating characteristic curve 0.85). Baseline LGE presence had no significant impact on MW deterioration during follow-up. MW is significantly impaired in HCM patients with myocardial fibrosis, highlighting potential utility of echocardiography-derived MW analysis as a valuable tool.
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Lion's Mane (Hericium erinaceus) has historically been used as traditional medicine in Asia and Europe for its potential benefits in fighting infection and cancer. It has gained interest in the neurodegenerative disease field because of its mechanisms of action; these include anti-inflammation, neuroprotection, and promoting neurite growth demonstrated in various cell and animal models. A very small, double-blind, placebo-controlled trial in patients with mild cognitive impairment showed a temporary improvement in cognitive function; this finding has yet to be replicated. However, there have been no studies in ALS cell or animal models or in humans with ALS. Lion's Mane appears safe and inexpensive when consumed in powder or capsule, but one anaphylactic case was reported after a patient consumed fresh Lion's Mane mushroom. Currently, we do not have enough information to support the use of Lion's Mane for treating ALS. We support further research in ALS disease models and clinical trials to study its efficacy.
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Agaricales , Esclerosis Amiotrófica Lateral , Enfermedades Neurodegenerativas , Animales , Humanos , Europa (Continente)RESUMEN
Aligned and suspended carbon nanotubes can outperform randomly oriented networks in electronic biosensing and thin-film electronics. However, carbon nanotubes tend to bundle and form random networks. Here, we show that carbon nanotubes spontaneously align in an ammonium deoxycholate surfactant gel even under low shear forces, allowing direct writing and printing of nanotubes into electrically conducting wires and aligned thin layers across trenches. To demonstrate its application potential, we directly printed arrays of disposable electrical biosensors, which show femtomolar sensitivity in the detection of DNA and SARS-CoV-2 RNA.
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Técnicas Biosensibles , Nanotubos de Carbono , ARN Viral , Electrónica , ElectricidadRESUMEN
OBJECTIVES: The COVID-19 pandemic affected medical care for chronic diseases. This study aimed to systematically assess the pandemic impact on oncological care in Germany using a rapid review. METHODS: MEDLINE, Embase, study and preprint registries and study bibliographies were searched for studies published between 2020 and 2 November 2022. Inclusion was based on the PCC framework: population (cancer), concept (oncological care) and context (COVID-19 pandemic in Germany). Studies were selected after title/abstract and full-text screening by two authors. Extracted data were synthesized using descriptive statistics or narratively. Risk of bias was assessed and summarized using descriptive statistics. RESULTS: Overall, 77 records (59 peer-reviewed studies and 18 reports) with administrative, cancer registry and survey data were included. Disruptions in oncological care were reported and varied according to pandemic-related factors (e.g., pandemic stage) and other (non-pandemic) factors (e.g., care details). During higher restriction periods fewer consultations and non-urgent surgeries, and delayed diagnosis and screening were consistently reported. Heterogeneous results were reported for treatment types other than surgery (e.g., psychosocial care) and aftercare, while ongoing care remained mostly unchanged. The risk of bias was on average moderate. CONCLUSIONS: Disruptions in oncological care were reported during the COVID-19 pandemic in Germany. Such disruptions probably depended on factors that were insufficiently controlled for in statistical analyses and evidence quality was on average only moderate. Research focus on patient outcomes (e.g., longer term consequences of disruptions) and pandemic management by healthcare systems is potentially relevant for future pandemics or health emergencies.
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ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here, we review caffeine which has plausible mechanisms for slowing ALS progression. However, pre-clinical studies are contradictory, and a large case series showed no relationship between caffeine intake and ALS progression rate. While low doses of caffeine are safe and inexpensive, higher doses can cause serious side effects. At this time, we cannot endorse caffeine as a treatment to slow ALS progression.
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Background Blood speckle tracking echocardiography allows for direct quantification of interventricular and aortic flow profiles, principally in children. Here, we sought to demonstrate the feasibility and reproducibility of blood speckle tracking echocardiography in the aortas of healthy children. Methods and Results One hundred healthy White children evaluated for the screening of congenital heart disease were prospectively enrolled. Echocardiographic examinations were performed using a Vivid E 95 ultrasound system, with blood speckle tracking from a focused and zoomed view of the aortic root and the ascending aorta. Vortex position, height (mm), width (mm), sphericity index, and area (cm2) were measured and indexed by body surface area. Median (interquartile range) age was 8.2 (5.6-11.0) years, median (interquartile range) weight was 28 (19-35) kg, and median (interquartile range) body surface area was 1.01 (0.79-1.16) m2. Vortices were visualized in only a single phase of the cardiac cycle in 25 subjects-14 (56.0%) were evident in early diastole and 11 (44.0%) in late systole. Vortices visualized in diastole had a mean area of 0.27±0.1 cm2/m2, while those in systole had a mean area of 0.34±0.12 cm2/m2. In a subset of 20 patients, inter- and intraobserver coefficient of variation and intraclass correlation coefficients were determined and showed good reproducibility. Conclusions We demonstrate feasibility and reproducibility of blood speckle tracking and identified vortical flow patterns in the aortic root and ascending aorta in healthy children. These data may serve as a baseline for evaluating aortic flow patterns in children with congenital and acquired heart disease.
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Ecocardiografía , Cardiopatías Congénitas , Humanos , Niño , Reproducibilidad de los Resultados , Ecocardiografía/métodos , Aorta/diagnóstico por imagen , Ultrasonografía , Cardiopatías Congénitas/diagnóstico por imagenRESUMEN
Background: Population-based cancer survival estimates can provide insight into the real-world impacts of healthcare interventions and preventive services. However, estimation of survival rates obtained from population-based cancer registries can be biased due to missed incidence or incomplete vital status data. Long-term survival estimates in particular are prone to overestimation, since the proportion of deaths that are missed, for example through unregistered emigration, increases with follow-up time. This also applies to registry-based long-term prevalence estimates. The aim of this report is to introduce a method to detect missed deaths within cancer registry data such that long-term survival of cancer patients does not exceed survival in the general population. Methods: We analyzed data from 15 German epidemiologic cancer registries covering the years 1970-2016 and from Surveillance, Epidemiology, and End Results (SEER)-18 registries covering 1975-2015. The method is based on comparing survival times until exit (death or follow-up end) and ages at exit between deceased patients and surviving patients, stratified by diagnosis group, sex, age group and stage. Deceased patients with both follow-up time and age at exit in the highest percentile were regarded as outliers and used to fit a logistic regression. The regression was then used to classify each surviving patient as a survivor or a missed death. The procedure was repeated for lower percentile thresholds regarding deceased persons until long-term survival rates no longer exceeded the survival rates in the general population. Results: For the German cancer registry data, 0.9% of total deaths were classified as having been missed. Excluding these missed deaths reduced 20-year relative survival estimates for all cancers combined from 140% to 51%. For the whites in SEER data, classified missed deaths amounted to 0.02% of total deaths, resulting in 0.4 percent points lower 20-year relative survival rate for all cancers combined. Conclusion: The method described here classified a relatively small proportion of missed deaths yet reduced long-term survival estimates to more plausible levels. The effects of missed deaths should be considered when calculating long-term survival or prevalence estimates.
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Post hypoxic myoclonus (PHM) is considered a poor prognostic sign and may influence decisions regarding withdrawal of treatment. PHM is generally categorized in literature as either acute or chronic (also commonly referred to as Lance-Adams Syndrome) based on the onset of myoclonus. However, it may be more accurate to differentiate between the various presentations of PHM based on the clinical characteristics and electroencephalogram (EEG) findings for prognostication. Here, we describe a case of a 33-year-old female who presented after a cardiopulmonary arrest. MRI of the brain and cervical spine on admission were unremarkable. Twelve hours later, she developed generalized, stimulus-sensitive myoclonus suggestive of acute PHM. Various medications were trialed, and her symptoms eventually improved on clonazepam. On day 14, she started having resting and intention myoclonus, and dysarthria, consistent with LAS. Several adjustments were again made to her regimen, and she was eventually switched from clonazepam to baclofen which improved her resting myoclonus. This case highlights that PHM can present differently and have a markedly different outcome. It is important to develop a better understanding of the various types of PHM so as to avoid premature withdrawal of care.
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ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review astaxanthin which has plausible mechanisms for slowing ALS progression including antioxidant, anti-inflammatory, and anti-apoptotic effects. While there are no ALS-specific pre-clinical studies, one verified "ALS reversal" occurred in a person using a combination of alternative therapies which included astaxanthin. There have been no trials of astaxanthin in people living with ALS. Natural astaxanthin appears to be safe and inexpensive. Based on the above information, we support further pre-clinical and/or clinical trials of astaxanthin in disease models and PALS, respectively, to further elucidate efficacy.
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Esclerosis Amiotrófica Lateral , Terapias Complementarias , Humanos , Esclerosis Amiotrófica Lateral/tratamiento farmacológicoRESUMEN
BACKGROUND: Myocardial work (MW) is an index of LV function based on pressure-strain loops and brachial cuff pressure measurement. MW has been proposed as more sensitive than conventional functional parameters, as it accounts for afterload and myocardial deformation. However, many studies have been limited to assessment of global MW indices, neglecting regional differences in cardiac associated with hypertension and consequent cardiac remodeling. We aimed to quantify regional MW in pediatric hypertension and compare the findings in renal or renovascular hypertension (RHTN) with essential hypertension (EHTN). METHODS: We retrospectively assessed conventional markers of LV function, and both global and regional MW indices in 78 patients (49 males, 15.4 ± 2.94 years) with EHTN and RHTN. RESULTS: Peak systolic strain (PSS) in the basal septal segment was significantly impaired in patients with RHTN compared to EHTN (-13.00% [-15.50%; -13.00%] vs. -15.00% [-17.50%; -13.50%], P = 0.034). Similarly, basal septal MW indices were significantly elevated in patients with EHTN compared to RHTN, including MW efficiency (MWE) (95.0% [93.0%; 98.0%] vs. 94.0% [89.0%; 95.0%], P = 0.004) and constructive work (CW) (1700 mm Hg% (409 mm Hg%) vs. 1520 mm Hg% (336 mm Hg%), P = 0.037). Wasted work (WW) was significantly elevated in the RHTN group (79.0 mm Hg% [28.5 mm Hg%; 104 mm Hg%] vs. 105 mm Hg% [62.0 mm Hg%; 164 mm Hg%], P = 0.010). CONCLUSION: Significant differences in basal septal PSS and MW indices were observed between EHTN and RHTN. These findings highlight the usefulness of regional MW indices in assessing disease and may help differentiate between etiologies of pediatric hypertension.
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Hipertensión Renovascular , Hipertensión , Masculino , Humanos , Niño , Estudios Retrospectivos , Corazón , Función Ventricular Izquierda , Volumen SistólicoRESUMEN
ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review ozone therapy. Ozone therapy has possible mechanisms for slowing ALS progression based on its antioxidant, anti-inflammatory, and mitochondrial effects. A non-peer-reviewed report suggests that ozone treatment may slow progression in a mTDP-43 mouse model of ALS. One verified "ALS reversal" occurred on a cocktail of alternative treatments including ozone. There are no ALS trials using ozone to treat PALS. There can be potentially serious side effects associated with ozone therapy, depending on the dose. Based on the above information, we support an investigation of ozone therapy in ALS cell or animal models but cannot yet recommend it as a treatment in PALS.
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Esclerosis Amiotrófica Lateral , Ratones , Animales , Humanos , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Modelos Animales de Enfermedad , MitocondriasRESUMEN
ALSUntangled reviews alternative and off-label treatments on behalf of people with ALS who ask about them. Here we review rituximab, a drug which specifically depletes B lymphocytes. We show a current lack of evidence for a role of these cells in ALS progression. The one patient we found who described using Rituximab for their ALS found no benefit. Given all this, and the known serious risks of rituximab, we advise against its use as an ALS treatment.
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Esclerosis Amiotrófica Lateral , Rituximab , Humanos , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Uso Fuera de lo Indicado , Rituximab/uso terapéuticoRESUMEN
Experimental data on pulmonary regurgitation has linked right ventricular longitudinal function to left ventricular filling pressure in animals with induced and treated pulmonary regurgitation but this relationship has not been investigated in patients with repaired Tetralogy of Fallot (rToF). The aim of this study was to determine if right ventricular longitudinal function assessed using cardiovascular magnetic resonance (CMR) is associated with left ventricular filling pressure in patients with rToF. A second objective of this study was to determine if direction of septal movement is related to right ventricular pressure load in rToF. Eighteen patients with rToF undergoing CMR and heart catheterization prior to pulmonary valve replacement were retrospectively included and catheter-based pressure measurements were compared with CMR-derived RV regional function. Left ventricular filling pressure was measured as precapillary wedge pressure (PCWP). Longitudinal contribution to RV stroke volume correlated with PCWP (r = 0.48; p = 0.046) but not with RV EF or pulmonary regurgitation. Neither RV longitudinal strain nor TAPSE showed correlation with PCWP. Longitudinal contribution to stroke volume was lower for the RV compared to the LV (49 vs 54%; p = 0.039). Direction of septal movement did not show a correlation with RV end-systolic pressure. Right ventricular longitudinal pumping is associated with left ventricular filling pressure in rToF-patients and this inter-ventricular coupling may explain LV underfilling in patients with pulmonary regurgitation and rToF and may be of value to determine right ventricular dysfunction. RV systolic pressure, however, cannot be assessed from the direction of septal movement, in these patients.
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Insuficiencia de la Válvula Pulmonar , Tetralogía de Fallot , Disfunción Ventricular Derecha , Humanos , Estudios Retrospectivos , Valor Predictivo de las Pruebas , Imagen por Resonancia Magnética , Función Ventricular DerechaRESUMEN
ALSUntangled reviews alternative and off-label treatments for people with amyotrophic lateral sclerosis (PALS). Here we review glucocorticoids. Neuroinflammation plays a prominent role in amyotrophic lateral sclerosis (ALS) pathogenesis, so some hypothesize that glucocorticoids might be an effective ALS therapy through their immunosuppressive effects. In this paper, we review the available evidence for glucocorticoids in ALS, including one pre-clinical study with a genetic mouse model of ALS, nine case reports (ranging from 1 to 26 patients each), and four clinical trials. We also review the possible side effects (including steroid myopathy) and the costs of therapy. We graded the level of evidence as follows: Mechanism, D; Pre-Clinical, F; Cases, B; Trials, F; Risks, C. Our review of the current evidence concludes that glucocorticoids do not offer clinical benefit in ALS and confer serious risks. Thus, ALSUntangled does not recommend glucocorticoids as a treatment for ALS.
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Esclerosis Amiotrófica Lateral , Humanos , Ratones , Animales , Esclerosis Amiotrófica Lateral/genética , Glucocorticoides/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
ALSUntangled reviews alternative and off label treatments with a goal of helping patients make more informed decisions about them. Here we review ketogenic diets. We shows that these have plausible mechanisms, including augmenting cellular energy balance and reducing excitotoxicity, neuroinflammation and oxidative stress. We review a mouse model study, anecdotal reports and trials in ALS and other diseases. We conclude that there is yet not enough data to recommend ketogenic diets for patients with ALS, especially in light of the many side effects these can have.
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Esclerosis Amiotrófica Lateral , Dieta Cetogénica , Animales , Humanos , Ratones , Esclerosis Amiotrófica Lateral/dietoterapia , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Since the beginning of the COVID-19 pandemic, there has been a high demand for rapid evidence syntheses to answer urgent public health questions. This article provides an overview of different types of reviews for public health questions and a synthesis of existing recommendations for the preparation of reviews. The aim is to support the planning of one's own review and the critical evaluation of published reviews. METHODS: The basis of this summary is an extensive search for guidelines and recommendations for different review types. Furthermore, internal journal clubs were held to determine knowledge needs and to critically discuss the various review types. Relating to the dissemination of results, fact sheets were developed for the individual review types including the most important information, prerequisites and work steps, as well as a decision tree for identifying the appropriate review type for the respective question. RESULTS: Of the review types identified, Systematic, Rapid, Scoping, Umbrella, and Narrative Reviews were considered in more detail because they are particularly relevant to public health issues. Together with scoping and umbrella reviews, systematic reviews have the highest resource requirements due to the demands for extensive, systematic evidence synthesis and reproducibility. Rapid methods can accelerate the review process, for example by a very narrowly formulated question, a limited literature search, or the execution of certain steps by one instead of two persons. DISCUSSION: Systematic Reviews may be considered as the gold standard, but they were developed primarily for clinical questions relating to interventions. This article, however, focusses on review types that consider the diversity of questions as well as the predominant use of quantitative methods in the field of public health. The fact sheets developed and the decision tree should enable low-threshold access to reviews while linking the perspectives of research and resource planning. They complement existing guidelines and recommendations. CONCLUSION: To answer the diverse spectrum of public health questions, various types of reviews with various requirements and approaches are available. Given this diversity, a systematic introduction can be helpful for researchers planning or assessing a review.