Large-cell neuroendocrine carcinoma of the lung (LCNEC) is a rare disease with poor prognosis and limited treatment options. Neuroendocrine tumors frequently show overactivation of the mTOR pathway. ...Based on the good activity of the mTOR inhibitor everolimus in different types of neuroendocrine tumors and the results of a previous phase I trial, we evaluated the efficacy and safety of everolimus in combination with carboplatin and paclitaxel as upfront treatment for patients with advanced LCNEC.
In this prospective, multicenter phase II trial chemotherapy-naive patients with stage IV LCNEC received 5 mg everolimus daily combined with paclitaxel 175 mg/m2 and carboplatin AUC 5 every 3 weeks for a maximum of four cycles followed by maintenance everolimus 5 mg daily until progression. Efficacy parameters were determined based on central radiologic assessment.
Forty-nine patients with a mean age of 62 ±9 years and a predominance of male (71%) smokers (98%) were enrolled in 10 German centers. The overall response rate was 45% (95% confidence interval CI 31%–60%), the disease control rate 74% (CI 59%–85%), the median progression-free survival 4.4 (CI 3.2–6) months and the median overall survival 9.9 (CI 6.9–11.7) months. The progression-free survival rate at 3 months (primary end point) was 76% (CI 64%–88%) according to Kaplan–Meier. Grade-3/4 toxicities occurred in 51% of patients and mainly consisted of general physical health deterioration (8%), cytopenias (24%), infections (10%) and gastrointestinal problems (8%). Typical everolimus-related adverse events, like stomatitis, rash and ocular problems occurred only in a minority of patients (<15%) and were exclusively of grade 1–2.
Everolimus in combination with carboplatin and paclitaxel is an effective and well-tolerated first-line treatment for patients with metastatic LCNEC.
EudraCT number 2010-022273-34, NCT01317615.
To evaluate the incremental risk of congenital heart disease on mortality after noncardiac surgery in children.
We reviewed the clinical information network database of the University Hospital ...Consortium for the period January 1, 1993, through December 31, 1996, and identified 191 261 patients <18 years old having 1 or more noncardiovascular surgical procedures. Of these patients, 6.5% had a diagnosis of congenital heart disease. Patients having ambulatory surgery are excluded from this database. Short-term (1-, 2-, and 3-day) and 30-day mortality were compared, as well as mortality for neonates, infants (31 days to 1 year), and older children (1-17 years); mortality for the 100 most common surgical procedures, mortality for 10 relatively minor surgical procedures, and mortality in subgroups of patients with minor versus severe cardiac diagnoses.
Short-term and 30-day mortality was increased in the patients with congenital heart disease patients (30-day mortality odds ratio 3.5; 95% confidence limit, 3.2-3.9). Mortality was also increased in patients with congenital heart disease in the 2 youngest age groups, for the 100 most common operations, and for 10 relatively minor operations. Children with more severe heart disease diagnoses had higher mortality than did children carrying less serious cardiac diagnoses.
A diagnosis of congenital heart disease adds significant incremental risk of mortality in children requiring inpatient noncardiovascular surgery. This outcome difference is present for both minor and major surgical procedures, and regardless of whether mortality is measured at 1, 3, or 30 days. The incremental risk is greatest in neonates and infants where the presence of congenital heart disease is associated with a 2-fold increase in mortality from noncardiac surgery.
Background
Adolescent and young adult oncology (AYAO) patients and caregivers may experience significant psychosocial dysfunction and financial toxicity. Understanding early risk factors is critical ...to improving survivorship trajectories.
Methods
The authors conducted a cross‐sectional study of baseline survey data from a prospective cohort of AYAO patient‐caregiver dyads enrolled within 1 month of medical oncology treatment initiation. Posttraumatic stress symptoms (PTSS) were measured by the Impacts of Events Scale–Revised, and financial toxicity was measured with the Comprehensive Score (COst). The authors fit models of linear association between PTSS, financial toxicity, and other end points and pairwise associations of PTSS and financial toxicity within dyads.
Results
The analytic cohort contained 41 patients, 37 caregivers, and 34 complete dyads. Clinically‐concerning PTSS were observed among patients (44%) and caregivers (52%). The median COst scores were 20.0 for patients (quartiles, 12.5‐29.5) and 22.0 for caregivers (quartiles, 12.8‐26.0), which were consistent with high financial toxicity (patients, 46%; caregivers, 44%). PTSS were positively associated with financial toxicity (P = .013 for patients, P = .039 for caregivers), subjective distress (P < .001 for all), depressive (P < .001 for all) and anxiety symptoms (P = .005 for patients, P = .024 for caregivers), and poorer quality of life (P < .001 for patients, P = .003 for caregivers). A significant paired association was not found in PTSS (Pearson correlation coefficient PCC, 0.23; 95% confidence interval CI, −0.15 to 0.56). Financial toxicity was positively associated within dyads (PCC, 0.65; 95% CI, 0.36‐0.83).
Conclusions
At diagnosis, AYAO patients and caregivers exhibit substantial PTSS, which are associated with greater financial toxicity and other psychosocial distress.
At cancer diagnosis, adolescent and young adult oncology patients and caregivers exhibit substantial posttraumatic stress symptoms, which are associated with high financial toxicity and other psychosocial distress. In paired analyses, a significant association between patient and caregiver posttraumatic stress symptoms is not found; financial toxicity is positively associated within dyads.
Введение. Вероятность хирургического вмешательства всегда предопределяет стрессорное состояние индивидуума, поэтому целесообразен поиск путей оптимизации и (или) коррекции неблагоприятного ...воздействия. Цель исследования – выяснение механизма антистрессорной активности витамина В1 в условиях операционного вмешательства. Материал и методы. Интенсивность метаболического процесса исследовалась на лизатах крови доноров (п=19) и пациентов, страдающих раком желудка (п=64) третьей стадии, оперированных в плановом порядке в возрасте 51-70 лет, взятой из локтевой вены за трое суток до операции, после премедикации, в наиболее травматичный момент операции, после экстубации, а также в первые и третьи сутки послеоперационного периода. Хирургическое вмешательство проводилось под комбинированной многокомпонентной анестезией с использованием закиси азота, оксибутирата натрия и эпидуральной блокады. Содержание В1 и его производных в крови находили методом ион-парной обращенно-фазовой ВЭЖХ. Результаты. В крови доноров и пациентов, страдающих раком желудка, наблюдается повышенное содержание тиаминмонофосфата и свободного тиамина. Скорость гидролитической тиаминмонофосфатазной реакции при этом не высока. На этапах премедикации и максимальной травматичности концентрация монофосфорного эфира быстро снижается при активации монофосфатазы. Очевидно, что гидролиз тиаминмонофосфата является скорость-лимитирующим звеном обменного процесса витамина В1. Уровень свободного тиамина на всех этапах остается устойчиво повышенным. Тиаминмонофосфатазная активность проявляется при двух pH-оптимумах – 6,0 и 9,0. Гидролиз тиаминмонофосфата при pH 9,0 катализируется щелочной фосфатазой. В области pH 6,0, помимо тиаминмонофосфорного эфира, фермент гидролизует только п-нитрофенилфосфат, флавинмононуклеотид и фосфотирозин, что позволяет отнести его к кислой фосфатазе печёночного типа. Отмеченные изменения в обмене В1 в условиях стресса касаются главным образом некоферментных форм – тиаминмоно-, трифосфата и свободного тиамина, расходуемых на этапах восстановления тиолов как компонентов инсулиносинтеза. Выводы. Использование витамина В1 позволяет оптимизировать развитие стрессорной реакции на всех этапах хирургического лечения. Его защитное действие реализуется посредством активации инсулин-синтетической функции поджелудочной железы, повышающей уровень иммунореактивного инсулина в крови. Формирование наиболее благоприятных физиологических условий для инсулиносинтеза обеспечивает повышенный «фон» свободного тиамина, создающийся за счет гидролиза некоферментных форм витамина. Прослежена связь метаболизма тиамина с обменом В2 и регуляцией внутриклеточных сигнальных путей.
Recognizing that receiving healthcare can be time intensive and burdensome, time toxicity has been conceptualized as the time spent by patients seeking healthcare. This study investigates the ...association between age at diagnosis and time toxicity for patients with Metastatic Breast Cancer (MBC) and identifies major components of care that confer the greatest time toxicity.
We conducted a retrospective cohort study among patients with MBC aged 67 or older using the SEER-Medicare database. We assessed time toxicity using the number of encounter days patients interacted with the healthcare system per 100 days, within the first year of starting cancer treatment. We used a Poisson model to analyze the association between age and encounter days, adjusting for clinical and sociodemographic factors. We stratified the mean encounter days for each age cohort by treatment types.
The final sample included 2949 patients; 51.4% were between 70 and 79 years old, and 81.3% were white. Although unadjusted analysis showed an association between older age and more encounter days (Rate Ratio (RR) 1.12; 95% CI 1.02, 1.22), there was no significant association after adjusting for comorbidities and treatment type. Patients with more than three comorbidities had significantly higher encounter days compared to those without comorbidities RR 1.36 (95% CI 1.26, 1.46). Receipt of radiotherapy RR: 1.45 95% CI (1.37, 1.54) was associated with more encounter days compared to not receiving radiotherapy, while receipt of bone-modifying agents was associated with fewer encounter days compared to not using Bone modifying agents RR 0.75 (95% CI 0.70, 0.79).
Our study identified comorbidities and cancer treatment modality, including radiotherapy, as the factors affecting time toxicity in older patients with MBC. Assessment of an individual's comorbid medical conditions and types of treatment planned are crucial to understanding age-related impacts on encounter days and to support shared decision making in older patients.
For some professionally, vocationally, or technically oriented careers, curricula delivered in higher education establishments may focus on teaching material related to a single discipline. By ...contrast, multidisciplinary, interdisciplinary, and transdisciplinary teaching (MITT) results in improved affective and cognitive learning and critical thinking, offering learners/students the opportunity to obtain a broad general knowledge base. Chemistry is a discipline that sits at the interface of science, technology, engineering, mathematics, and medicine (STEMM) subjects (and those aligned with or informed by STEMM subjects). This article discusses the significant potential of inclusion of chemistry in MITT activities in higher education and the real-world importance in personal, organizational, national, and global contexts. It outlines the development and implementation challenges attributed to legacy higher education infrastructures (that call for creative visionary leadership with strong and supportive management and administrative functions), and curriculum design that ensures inclusivity and collaboration and is pitched and balanced appropriately. It concludes with future possibilities, notably highlighting that chemistry, as a discipline, underpins industries that have multibillion dollar turnovers and employ millions of people across the world.
Melanins are a class of biopolymers that are widespread in nature, with diverse origins, compositions, and functions, and their chemical and optoelectronic properties render them potentially useful ...for application in materials science for various biotechnological applications. For patients with alkaptonuria, the accumulation of homogentisic acid (HGA) in their bodies is associated with the concomitant deposition of pyomelanin, which is a pigment that contains significant amounts of polymerized HGA (polyHGA) in the bodily tissues of the patients. The polymerization of HGA under various different conditions in vitro is investigated using a selection of different analytical chemistry techniques to understand if there may be a correlation between the conditions and pigment deposition in vivo, and their potential for application as green/sustainable and components of electronic devices.
Homogentisic acid (HGA) polymerization to form polyHGA (a simplified version of pyomelanin) is investigated in the absence/presence of enzymes at physiologically relevant pH values. Their chemical, paramagnetic, and electrical properties are analyzed to assess if there may be a correlation between the conditions and pigment deposition in vivo and their prospects for use as sustainable resources for advanced biotechnological applications.
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•A method to distinguish forged from genuine £20 banknotes has been developed.•Spectra may be recorded from paper or polymer film areas of the note for this purpose.•The method may be ...used with a simple bench-top FTIR.•Results may be supported by the use of IR-microscopy.•The method could readily be adapted for use by non-laboratory trained personnel.
Bank of England notes of £20 denomination have been studied using infrared spectroscopy in order to generate a method to identify forged notes. An aim of this work was to develop a non-destructive method so that a small, compact Fourier transform infrared spectrometer (FT-IR) instrument could be used by bank workers, police departments or others such as shop assistants to identify forged notes in a non-lab setting. The ease of use of the instrument is the key to this method, as well as the relatively low cost. The presence of a peak at 1400cm−1 arising from νasym (CO32-) from the blank paper section of a forged note proved to be a successful indicator of the note’s illegality for the notes that we studied. Moreover, differences between the spectra of forged and genuine £20 notes were observed in the ν(OH) (ca. 3500cm−1), ν(CH) (ca. 2900cm−1) and ν(CO) (ca. 1750cm−1) regions of the IR spectrum recorded for the polymer film covering the holographic strip. In cases where these simple tests fail, we have shown how an infrared microscope can be used to further differentiate genuine and forged banknotes by producing infrared maps of selected areas of the note contrasting inks with background paper.
A simple, specific and sensitive HPLC assay for levofloxacin in serum, bile, soft tissue and bone was evaluated and validated. The samples were prepared by protein precipitation with acids and ...methanol, which yielded high recoveries (for serum and bile>98% and for bone and soft tissue>90%). The compounds were separated on a reversed phase column with an acidic mobile phase containing triethylamine. The eluate was monitored by fluorescence detection. The HPLC assay is linear over the usable concentration range (0.1-40 microg/ml) and it provides good validation data for accuracy and precision. Although comparison of HPLC results to the results of a microbiological assay showed congruent results (regression coefficients>0.967). HPLC should be the method of choice for determination of levofloxacin in biological matrices.
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