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Approved spectrofluorimetric strategies for assurance of three modern antineoplastic drugs; Tepotinib, Sotorasib and Darolutamide in their dose forms and biological liquids utilizing mercurochrome

Luminescence. 2022 Feb 10. doi: 10.1002/bio.4206. Online ahead of print.

ABSTRACT

Approved, straightforward, fast and delicate spectrofluorimetric strategy has been developed for the estimation of tepotinib (TEPO), sotorasib (SOTO) and darolutamide (DARO) as a new antineoplastic drugs. Spectrofluorimetric strategy was based on quantitative fluorescence quenching of MER at 538 nm after being excited at 350 nm by the addition of cited drugs in presence of acetate buffer (pH 3.5). The degree of fluorescence quenching is directly proportional to the concentrations of the cited drugs within the concentration range of 0.5-10.0, 0.2-10 and 0.4-10.0 μg mL-1 for TEPO, SOTO and DARO, respectively. Mean ± S.D. were calculated for the studied drugs as follows; 99.9±0.87, 99.72±1.08 and 100.21±1.44, for TEPO, SOTO and DARO, respectively. LOD values were 0.16, 0.05 and 0.11 μg mL-1 while LOQ values were 0.5, 0.15 and 0.36 μg mL-1 for TEPO, SOTO and DARO, respectively. Statistical comparison of comes about with those gotten by detailed strategies given great understanding and uncovered that there were no noteworthy contrasts in exactness and exactness between strategies. The proposed strategy was connected effectively to analyze measurement shapes containing the examined drugs. Moreover, the recommended fluorimetric strategy was connected for examination of TEPO, SOTO and DARO in human plasma and urine test.

PMID:35142060 | DOI:10.1002/bio.4206

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Serum IL-35 levels is a new candidate biomarker of cancer-related cachexia in stage IV non-small cell lung cancer

Thorac Cancer. 2022 Feb 9. doi: 10.1111/1759-7714.14307. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer-related cachexia is a major cause of treatment resistance and poor prognosis, which is characterized by anorexia and skeletal muscle depletion. To date, there have been no reports on the relationship between IL-35 and cancer-related cachexia in patients with stage IV non-small cell lung cancer.

METHODS: Serum IL-35 levels in 86 patients with stage IV NSCLC were measured and statistically analyzed based on patients’ clinicopathological parameters. Serum albumin levels, C-reactive protein, and skeletal muscle index (SMI) of the patients were also determined. In vivo studies using a mouse model were also conducted by subcutaneously injecting immunodeficiency (SCID) mice with overexpressing IL-35 cell lines and determining their daily food intake, bodyweight and muscle atrophy. Cachexia indicators were measured again after administering the mice with an anti-IL35 neutralizing antibody.

RESULTS: Patients with stage IV NSCLC had significantly higher serum IL-35 levels than the healthy controls. Similarly, circulating IL-35 levels were significantly higher in patients with cachexia than those without. The SMI values of patients with high serum IL-35 levels were significantly lower than those with low serum IL-35 levels. Mice subcutaneously injected with LLC PLV-IL-35 cell lines exhibited anorexia, weight loss, and muscle atrophy. Moreover, these symptoms were significantly reduced after administering the mice with an anti-IL35 neutralizing antibody.

CONCLUSIONS: This study reveals that high serum IL-35 expression is associated with non-small cell lung cancer cachexia and skeletal muscle atrophy. These findings highlight its potential as a biomarker and therapeutic target for controlling cachexia of advanced lung cancer.

PMID:35142058 | DOI:10.1111/1759-7714.14307

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Selecting Candidates for Organ-Preserving Strategies After Neoadjuvant Chemoradiotherapy for Rectal Cancer: Development and Validation of a Model Integrating MRI Radiomics and Pathomics

J Magn Reson Imaging. 2022 Feb 10. doi: 10.1002/jmri.28108. Online ahead of print.

ABSTRACT

BACKGROUND: Histopathologic evaluation after surgery is the gold standard to evaluate treatment response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). However, it cannot be used to guide organ-preserving strategies due to poor timeliness.

PURPOSE: To develop and validate a multiscale model incorporating radiomics and pathomics features for predicting pathological good response (pGR) of down-staging to stage ypT0-1N0 after nCRT.

STUDY TYPE: Retrospective.

POPULATION: A total of 153 patients (median age, 55 years; 109 men; 107 training group; 46 validation group) with clinicopathologically confirmed LARC.

FIELD STRENGTH/SEQUENCE: A 3.0-T; fast spin echo T2 -weighted and single-shot EPI diffusion-weighted images.

ASSESSMENT: The differences in clinicoradiological variables between pGR and non-pGR groups were assessed. Pretreatment and posttreatment radiomics signatures, and pathomics signature were constructed. A multiscale pGR prediction model was established. The predictive performance of the model was evaluated and compared to that of the clinicoradiological model.

STATISTICAL TESTS: The χ2 test, Fisher’s exact test, t-test, the minimum redundancy maximum relevance algorithm, the least absolute shrinkage and selection operator logistic regression algorithm, regression analysis, receiver operating characteristic curve (ROC) analysis, Delong method. P < 0.05 indicated a significant difference.

RESULTS: Pretreatment radiomics signature (odds ratio [OR] = 2.53; 95% CI: 1.58-4.66), posttreatment radiomics signature (OR = 9.59; 95% CI: 3.04-41.46), and pathomics signature (OR = 3.14; 95% CI: 1.40-8.31) were independent factors for predicting pGR. The multiscale model presented good predictive performance with areas under the curve (AUC) of 0.93 (95% CI: 0.88-0.98) and 0.90 (95% CI: 0.78-1.00) in the training and validation groups, those were significantly higher than that of the clinicoradiological model with AUCs of 0.69 (95% CI: 0.55-0.82) and 0.68 (95% CI: 0.46-0.91) in both groups.

DATA CONCLUSION: A model incorporating radiomics and pathomics features effectively predicted pGR after nCRT in patients with LARC.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 4.

PMID:35142001 | DOI:10.1002/jmri.28108

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Health-related quality of life and menstrual problems in adolescents

J Paediatr Child Health. 2022 Feb 10. doi: 10.1111/jpc.15895. Online ahead of print.

ABSTRACT

AIM: To evaluate whether the health-related quality-of-life (HRQoL) scores would be different for adolescents with menstrual problems as compared to those with normal menstruation after taking into account clinical, socio-demographic and life-style factors.

METHODS: The Paediatric Quality of Life Inventory 4.0 scale was used to assess HRQoL in 126 schoolgirls of 16 ± 0.4 years old. The adolescents completed semi-structured questionnaires containing information on social and demographic characteristics, life-style features and menstrual questionnaires that included the following: age of menstruation, menstrual cycle length, duration of production, the number of pads used per day, menstrual pain and drug administration to relieve dysmenorrhea. The menstrual problems were classified into three main groups: dysmenorrhoea, oligomenorrhoea, and heavy menstrual bleeding. Anthropometric measurements were performed by a physician. Medical history was obtained from school medical charts.

RESULTS: Ninety-seven (77%) girls had menstrual problems. Dysmenorrhoea (n = 92, 73%) was the most frequent of these, followed by oligomenorrhoea (n = 13, 10.3%) and heavy menstrual bleeding (n = 6, 4.8%). Thirteen (10.3%) girls had combined disorders. A multivariate analysis adjusted for life-style factors found an independent association of any menstrual problems, oligomenorrhoea and dysmenorrhoea with low HRQoL scores in the emotional functioning domain. For adolescents with oligomenorrhoea, an association with low total scale scores was also shown but it did not reach statistical significance.

CONCLUSION: The prevalence of menstrual problems is high among schoolgirls. Medical professionals working with adolescents should know that girls with menstrual problems are highly likely to have a poor quality of life, especially those with oligomenorrhoea.

PMID:35141982 | DOI:10.1111/jpc.15895

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Regional citrate and systemic heparin are adequate to maintain filter half-life for COVID-19 patients on continuous renal replacement therapy

Semin Dial. 2022 Feb 9. doi: 10.1111/sdi.13061. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of our study is to compare clotting of CRRT filters in patients with COVID-19-associated AKI versus septic shock-associated AKI.

METHODS: Retrospective study of adult ICU patients with COVID-19 compared to those with septic shock admitted to a tertiary hospital April-October 2020. Independent t test and chi-square test used to determine statistical significance of CRRT filter clotting between the two groups. Time-to-event data analyzed with Kaplan-Meier curves. Analyses performed on Microsoft Excel and MedCalc.

RESULTS: Twenty-seven ICU patients with AKI requiring CRRT were included, 13 with COVID-19 and 14 non-COVID-19 patients with septic shock. The mean half-life of CRRT hemofilter was similar in COVID-19 patients compared to non-COVID-19 patients (27.4 vs. 27.5 h, p = 0.79). The number of CRRT hemofilter changes per day was similar in both groups (0.6 filter changes per day, p = 0.84). However, significantly more patients with COVID-19 were on systemic heparin (69% vs. 13%, p = 0.02).

CONCLUSION: We found that COVID-19 patients with AKI requiring CRRT had similar CRRT hemofilter half-life compared with sepsis-associated AKI patients with use of regional citrate and systemic heparin. Further studies are needed to find which methods of anticoagulation are optimal in patients with COVID-19 infection with AKI requiring CRRT.

PMID:35141966 | DOI:10.1111/sdi.13061

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Supplemental or dietary intake of omega-3 fatty acids for the treatment of periodontitis: A meta-analysis

J Clin Periodontol. 2022 Feb 10. doi: 10.1111/jcpe.13603. Online ahead of print.

ABSTRACT

AIM: This study evaluated the intervention effect of omega-3 fatty acids on changes in periodontal parameters.

MATERIALS AND METHODS: This meta-analysis included English-language studies published between 2010 and 2020, which were extracted from the Cochrane Library, EMBASE, and PubMed databases. The effects of omega-3 fatty acid intervention were investigated using the amount of omega-3 intake, periodontal pocket depth (PPD), clinical attachment loss (CAL), and bleeding on probing (BOP). The random-effects model was generated for data analysis. To obtain robustness of the model, sensitivity analysis was implemented. Subgroup analyses were performed based on the intervention period for each parameter.

RESULTS: All 13 studies included in the meta-analysis were interventional randomized controlled trials. Two studies implemented omega-3 fatty acid-rich diets, while eleven studies used supplements. Risk of bias was low and publication bias was not shown. Meta-analysis showed a statistically significant PPD reduction (standardized mean difference; SMD = -0.81 mm, absolute mean difference; MD = -0.44 mm), CAL gain (SMD = -0.77 mm, MD = -0.51 mm), and BOP reduction (SMD = -0.65%, MD = -9.45%) for the omega-3 fatty acids intervention overall.

CONCLUSION: This study suggests that supplemental or dietary intake of omega-3 fatty acids for the treatment of periodontitis may positively impact on periodontitis.

PMID:35141945 | DOI:10.1111/jcpe.13603

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The relationship between bioelectrical impedance parameters and pulmonary artery stiffness in obese subjects

Echocardiography. 2022 Feb 9. doi: 10.1111/echo.15320. Online ahead of print.

ABSTRACT

OBJECTIVES: Obesity is a public health problem that needs to be treated and it occurs as a result of excessive fat accumulation in the body. The relationship between obesity and pulmonary hypertension is well known. The aim of this study is to evaluate the relationship between pulmonary artery stiffness, right ventricular functions and bioelectrical impedance parameters in obese, overweight, and healthy individuals.

METHODS: In this study, 41 obese (17 female and 24 male, mean age 43.5±10.3), 39 overweight (20 female and 19 male, mean age 38.6±10.4), 34 healthy control group (19 female and 15 male, mean age 40.5±8.6) were included. Anthropometric measurements and bioelectrical impedance parameters of all participants were performed. Right ventricular functions and pulmonary artery stiffness were evaluated by using conventional echocardiography.

RESULTS: Right ventricle myocardial performance index, pulmonary artery stiffness values were statistically different between groups. Positive correlation was observed between pulmonary artery stiffness and Body Mass Index, Waist and Hip circumferences. Significant negative correlation was observed between muscle to fat ratio and pulmonary artery stiffness. In the linear regression analysis, it was observed that the muscle to fat ratio was independent predictor of pulmonary artery stiffness (β = -1.835; 95%CI(-2.434 – – .784); p < 0.001).

CONCLUSIONS: This study showed that right ventricular function was impaired and pulmonary artery stiffness increased in obese individuals. These findings could be considered as early markers of pulmonary hypertension in obese patients who do not yet have clinical evidence of cardiovascular disease.

PMID:35141938 | DOI:10.1111/echo.15320

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A microfluidic approach for studying microcolonization of Escherichia coli O157:H7 on leaf trichome-mimicking surfaces under fluid shear stress

Biotechnol Bioeng. 2022 Feb 10. doi: 10.1002/bit.28057. Online ahead of print.

ABSTRACT

Escherichia coli O157:H7 have previously been associated with disease outbreaks associated with leafy green vegetables. However, the physical mechanisms that determine the spatial organization of bacteria onto leafy greens are still not clear. Microfluidics with embedded trichome-mimicking microposts were employed to investigate the role of shear flow and configuration of trichomes on E. coli O157:H7 microcolonization. We characterized the 3D microcolonization of green fluorescent protein (GFP)-tagged E. coli O157:H7 using multiphoton fluorescence microscopy and compared their differences under static (no flow; incubated for 36 h at 37°C) and fluid shear conditions (750 nL/min for 36 h at 37°C). For micropatterned trichome arrays, we demonstrated that natural wax-mixed polydimethylsiloxane (PDMS) retains similar topographies and contact angles to the surface of trichome-bearing leafy greens. Our results showed that E. coli O157:H7 under fluid shear stress aligned their colonization parallel to the direction of flow. In a static condition, their colonization had no preferential alignment, with statistically similar angular distributions in all directions. In addition, depending on dimensions of the trichome arrays and flow conditions, different bacterial microcolonization patterns grew radially from initial attachment; they formed into filamentous structures and developed into bridges by surface hydrophobicity and flow-induced shear with a nutrient-rich medium. Collectively, these results demonstrate how the consequences of bacterial colonization in response to shear flow can affect pathogenic bacterial contamination of leafy greens and biofilm architectures. This article is protected by copyright. All rights reserved.

PMID:35141878 | DOI:10.1002/bit.28057

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The Curing Coma Campaign International Survey on Coma Epidemiology, Evaluation, and Therapy (COME TOGETHER)

Neurocrit Care. 2022 Feb 9. doi: 10.1007/s12028-021-01425-8. Online ahead of print.

ABSTRACT

BACKGROUND: Although coma is commonly encountered in critical care, worldwide variability exists in diagnosis and management practices. We aimed to assess variability in coma definitions, etiologies, treatment strategies, and attitudes toward prognosis.

METHODS: As part of the Neurocritical Care Society Curing Coma Campaign, between September 2020 and January 2021, we conducted an anonymous, international, cross-sectional global survey of health care professionals caring for patients with coma and disorders of consciousness in the acute, subacute, or chronic setting. Survey responses were solicited by sequential emails distributed by international neuroscience societies and social media. Fleiss κ values were calculated to assess agreement among respondents.

RESULTS: The survey was completed by 258 health care professionals from 41 countries. Respondents predominantly were physicians (n = 213, 83%), were from the United States (n = 141, 55%), and represented academic centers (n = 231, 90%). Among eight predefined items, respondents identified the following cardinal features, in various combinations, that must be present to define coma: absence of wakefulness (81%, κ = 0.764); Glasgow Coma Score (GCS) ≤ 8 (64%, κ = 0.588); failure to respond purposefully to visual, verbal, or tactile stimuli (60%, κ = 0.552); and inability to follow commands (58%, κ = 0.529). Reported etiologies of coma encountered included medically induced coma (24%), traumatic brain injury (24%), intracerebral hemorrhage (21%), and cardiac arrest/hypoxic-ischemic encephalopathy (11%). The most common clinical assessment tools used for coma included the GCS (94%) and neurological examination (78%). Sixty-six percent of respondents routinely performed sedation interruption, in the absence of contraindications, for clinical coma assessments in the intensive care unit. Advanced neurological assessment techniques in comatose patients included quantitative electroencephalography (EEG)/connectivity analysis (16%), functional magnetic resonance imaging (7%), single-photon emission computerized tomography (6%), positron emission tomography (4%), invasive EEG (4%), and cerebral microdialysis (4%). The most commonly used neurostimulants included amantadine (51%), modafinil (37%), and methylphenidate (28%). The leading determinants for prognostication included etiology of coma, neurological examination findings, and neuroimaging. Fewer than 20% of respondents reported routine follow-up of coma survivors after hospital discharge; however, 86% indicated interest in future research initiatives that include postdischarge outcomes at six (85%) and 12 months (65%).

CONCLUSIONS: There is wide heterogeneity among health care professionals regarding the clinical definition of coma and limited routine use of advanced coma assessment techniques in acute care settings. Coma management practices vary across sites, and mechanisms for coordinated and sustained follow-up after acute treatment are inconsistent. There is an urgent need for the development of evidence-based guidelines and a collaborative, coordinated approach to advance both the science and the practice of coma management globally.

PMID:35141860 | DOI:10.1007/s12028-021-01425-8

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Association of Integrated Mental Health Services with Physical Health Quality Among VA Primary Care Patients

J Gen Intern Med. 2022 Feb 9. doi: 10.1007/s11606-021-07287-2. Online ahead of print.

ABSTRACT

BACKGROUND: Integrated care for comorbid depression and chronic medical disease improved physical and mental health outcomes in randomized controlled trials. The Veterans Health Administration (VA) implemented Primary Care-Mental Health Integration (PC-MHI) across all primary care clinics nationally to increase access to mental/behavioral health treatment, alongside physical health management.

OBJECTIVE: To examine whether widespread, pragmatic PC-MHI implementation was associated with improved care quality for chronic medical diseases.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 828,050 primary care patients with at least one quality metric among 396 VA clinics providing PC-MHI services between October 2013 and September 2016.

MAIN MEASURE(S): For outcome measures, chart abstractors rated whether diabetes and cardiovascular quality metrics were met for patients at each clinic as part of VA’s established quality reporting program. The explanatory variable was the proportion of primary care patients seen by integrated mental health specialists in each clinic annually. Multilevel logistic regression models examined associations between clinic PC-MHI proportion and patient-level quality metrics, adjusting for regional, patient, and time-level effects and clinic and patient characteristics.

KEY RESULTS: Median proportion of patients seen in PC-MHI per clinic was 6.4% (IQR=4.7-8.7%). Nineteen percent of patients with diabetes had poor glycemic control (hemoglobin A1c >9%). Five percent had severely elevated blood pressure (>160/100 mmHg). Each two-fold increase in clinic PC-MHI proportion was associated with 2% lower adjusted odds of poor glycemic control (95% CI=0.96-0.99; p=0.046) in diabetes. While there was no association with quality for patients diagnosed with hypertension, patients without diagnosed hypertension had 5% (CI=0.92-0.99; p=0.046) lower adjusted odds of having elevated blood pressures.

CONCLUSIONS AND RELEVANCE: Primary care clinics where integrated mental health care reached a greater proportion of patients achieved modest albeit statistically significant gains in key chronic care quality metrics, providing optimism about the expected effects of large-scale PC-MHI implementation on physical health.

PMID:35141854 | DOI:10.1007/s11606-021-07287-2