Randomized phase II trial of the clinical and biological effects of two dose levels of gefitinib in patients with recurrent colorectal adenocarcinoma.

PURPOSE: The clinical objective of this trial was to evaluate gefitinib in patients with metastatic colorectal cancer that had progressed despite prior treatment. Serial tumor biopsies were performed when possible and analyzed for activation of the epidermal growth factor receptor (EGFR) signaling pathway. Serial serum samples were measured for amphiregulin and transforming growth factor-alpha (TGFalpha). PATIENTS AND METHODS: One hundred fifteen patients were randomly assigned to receive gefitinib 250 or 500 mg orally once a day. One hundred ten patients were assessable for clinical efficacy. Biologic evaluation was performed on paired tumor samples from 28 patients and correlated with clinical outcome. RESULTS: Median progression-free survival was 1.9 months (95% CI, 1.8 to 2.1 months) and 4-month progression-free survival rate was 13% +/- 5%. One patient achieved a radiographic partial response (RR = 1%; 95% CI, 0.01% to 5%). Median survival was 6.3 months (95% CI, 5.1 to 8.2 months). The most common adverse events were skin rash, diarrhea, and fatigue. In the biopsy cohort, expression of total or activated EGFR, activated Akt, activated MAP-kinase, or Ki67 did not decrease following 1 week of gefitinib. However, a trend toward decreased post-treatment levels of activated Akt and Ki67 was observed in patients with a PFS higher than the median, although these did not reach the .05 level of significance. CONCLUSION: Gefitinib is inactive as a single agent in patients with previously treated colorectal cancer. In tumor samples, gefitinib did not inhibit activation of its proximal target, EGFR. Trends were observed for inhibition of downstream regulators of cellular survival and proliferation in patients achieving longer progression-free survival.     

Severe pulmonary hemorrhage in a 3‐week‐old neonate with COVID‐19 infection: A case report

Our patient is a 3‐week‐old female neonate, presented with complaints of low‐grade fever and a congested nose for one day. Eventually, she developed progressive desaturation, hypotension, and poor perfusion due to severe pulmonary hemorrhage. Then, she developed cardiac arrest and was declared dead.     

Long-Term Effect of Gluten-Free Diets on Nutritional Status,Body Composition,and Associated Factors in Adult Saudi Females with Celiac Disease

This cross-sectional study examines the influence of long-term gluten-free diet (GFD) consumption on nutritional status, body composition, and associated factors in adult Saudi females with celiac diseases (CD). Fifty-one patients who have been diagnosed with CD and have been on GFD for more than 1 year were included in this study where data regarding their dietary pattern, as well as a complete analysis of their anthropometric parameters, vitamins B12 and D levels, and complete blood count (CBC), were collected. Data have shown that all included patients showed a reduced intake in all micro and macro-nutrients, as well as vitamin D, folate, calcium, and iron. However, the vast majority of all measured hematological parameters and blood indices were within the expected reference range. In addition, 51%, 43.1%, and 60.8% of the patients showed low waist/hip ratio (WHR), decreased level of total body fat (BF), and decreased level of visceral fat (VF), respectively, whereas 33.3% were slim. The poor educational level and some psychosocial factors were associated with the poor nutritional status of the patients. In conclusion, the GFD-dependent intake by female patients with CD adversely affects their nutritional intake and anthropometric indices and leads to a deficiency in major nutrients, vitamins, and ions.     

Gemcitabine and Cisplatin as Neo-Adjuvant for Cholangiocarcinoma Patients Prior to Liver Transplantation: Case-Series

Background: The management of cholangiocarcinoma is continually reviewed on a current evidence basis to develop practice guidelines and consensus statements. However, the standardized treatment guidelines are still unclear for cholangiocarcinoma patients who are listed for liver transplantation. We aimed to validate and evaluate the potential efficacy of chemotherapy combination of Gemcitabine and Cisplatin as a neo-adjuvant treatment for cholangiocarcinoma patients before liver transplantation. Methods: In this prospective case series, patients with locally advanced, unresectable, hilar, or intrahepatic cholangiocarcinoma with no evidence of extrahepatic disease or vascular involvement were treated with a combination of neoadjuvant gemcitabine and cisplatin with no radiation. All patients included received chemotherapy prior to being listed for liver transplantation at a single cancer center according to an open-labeled, and center-approved clinical management protocol. The primary endpoints were the overall survival and recurrence-free survival after liver transplantation. Results: Between 1 March 2016, and 15 March 2022, 10 patients (8 males and 2 females) with a median age of 62.71(interquartile range: 60.02–71.87) had a confirmed diagnosis of intrahepatic or hilar cholangiocarcinoma and underwent liver transplantation. Median days of neoadjuvant therapy for a given combination of gemcitabine and cisplatin were 181 (IRQ: 120–250). Nine patients (90%) were reported with no recurrence or metastasis, and only 1 patient had confirmed metastasis (10%); days for metastasis after transplantation were 612 for this patient. All patients received a combination of gemcitabine and cisplatin as neo-adjuvant while awaiting liver transplantation. The median days of follow-up were 851 (813–967). Overall survival was 100% (95% CI 100–100%) at both years one and two; 75% (95% CI 13–96%) at years three to five. One patient died at eight hundred and eighty-five days. No adverse events were reported after liver transplantation including the patient who was confirmed with recurrence. Conclusions: Our finding demonstrated that neo-adjuvant gemcitabine and cisplatin with no radiation prior to liver transplantation resulted in excellent outcomes for patients with cholangiocarcinoma.     

Women's empowerment and fertility preferences of married women: analysis of demographic and health survey’2016 in Timor-Leste

A recently independent state, Timor-Leste, is progressing towards socioeconomic development, prioritizing women empowerment while its increased fertility rate (4.1) could hinder the growth due to an uncontrolled population. Currently, limited evidence shows that indicators of women''s empowerment are associated with fertility preferences and rates. The objective of this study was to assess the association between women empowerment and fertility preferences of married women aged 15 to 49 years in Timor-Leste using nationally representative survey data. The study was conducted using the data of the latest Timor-Leste Demographic and Health Survey 2016. The study included 4040 rural residents and 1810 urban residents of Timor-Leste. Multinomial logistic regression has been performed to assess the strength of association between the exposures indicating women''s empowerment and outcome (fertility preference). After adjusting the selected covariates, the findings showed that exposures that indicate women empowerment in DHS, namely, the employment status of women, house and land ownership, ownership of the mobile phone, and independent bank account status, contraceptive use, and the attitude of women towards negotiating sexual relations are significantly associated with fertility preferences. The study shows higher the level of education, the less likely were the women to want more children, and unemployed women were with a higher number of children. Our study also found that the attitude of violence of spouses significantly influenced women''s reproductive choice. However, employment had no significant correlation with decision-making opportunities and contraceptive selection due to a lack of substantial data. Also, no meaningful data was available regarding decision-making and fertility preferences. Our findings suggest that women''s empowerment governs decision-making in fertility preferences, causing a decline in the fertility rate.     

Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells

Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic invasomes (INVA) covered with Phospholipon 90G and apamin (APA). The Box–Behnken statistical design was implemented to enhance the composition. Using Design-Expert software (Stat-Ease Inc., Minneapolis, MN), the INVA component quantities were optimized to obtain spherical particles with the smallest size, that is, a diameter of 167.8 nm. 2ME-INVA-APA significantly inhibited A549 cells and exhibited IC₅₀ of 1.15 ± 0.04 µg/mL, which is lower than raw 2ME (IC₅₀ 5.6 ± 0.2 µg/mL). Post 2ME-INVA-APA administration, a significant rise in cell death and necrosis was seen among the A549 cells compared to those treated with plain formula or 2ME alone. This effect was indicated by increased Bax expression and reduced Bcl-2 expression, as well as mitochondrial membrane potential loss. Moreover, the cell cycle analysis showed that 2ME-INVA-APA arrests the G2-M phase of the A549 cells. Additionally, it was observed that the micellar formulation of the drug increased the cell count in pre-G1, thereby exhibiting phenomenal apoptotic potential. Furthermore, it up-regulates caspase-9 and p53 and downregulates TNF-α and NF-κβ. Collectively, these findings showed that our optimized 2ME-INVA-APA could easily seep through the cell membrane and induce apoptosis in relatively low doses.     

A Numerical Measurement Method for Dynamic Granular Materials Based on Computer Vision

Granular materials are widespread in nature and human production, and their macro-mechanical behavior is significantly affected by granule movement. The development of computer vision has brought some new ideas for measuring the numerical information (including the amount of translation, the rotation angle, velocity, acceleration, etc.) of dynamic granular materials. In this paper, we propose a numerical measurement method for dynamic granular materials based on computer vision. Firstly, an improved video instance segmentation (VIS) network is introduced to perform end-to-end multi-task learning, and its temporal feature fusion module and tracking head with long-sequence external memory can improve the problems of poor video data quality and high similarity in appearance of granular materials, respectively. Secondly, the numerical information can be extracted through a series of post-processing steps. Finally, the effectiveness of the measurement method is verified by comparing the numerical measurement results with the real values. The experimental results indicate that our improved VIS obtains an average precision (AP) of 76.6, the relative errors and standard deviations are maintained at a low level, and this method can effectively be used to measure the numerical information of dynamic granular materials. This study provides an intelligent proposal for the task of measuring numerical information of dynamic granular materials, which is of great significance for studying the spatial distribution, motion mode and macro-mechanical behavior of granular materials.     

Hemangioma of the maxillary sinus: A benign and rare cause of epistaxis

Hemangioma of the facial sinuses is a rare pathology, and given the lack of clinical specificity, the differential diagnosis with a malignant lesion often arises. We report the case of a 32-year-old patient who consulted for recurrent epistaxis of moderate severity. The preoperative diagnosis of a hemangioma of the left maxillary sinus was based on computed tomography and magnetic resonance imaging data, confirmed by the anatomopathological study of the surgical specimen, preceded by an embolization that facilitated the endoscopic surgical excision.     

Global Research Trends in Lithium Toxicity from 1913 to 2015: A Bibliometric Analysis

Lithium salts have been used to treat psychiatric disorders since the 1940s and are currently used in prophylaxis and treatment of depression and bipolar disorder. Therefore, we conducted this study to assess lithium toxicity‐related publications using bibliometric approaches from a health point of view to assess global research trends in the lithium toxicity field to offer guidance to future research in this field. The data were retrieved from the online version of Scopus database on 6 August 2016. All records with the term ‘lithium’ in the title were retrieved, and those related to lithium toxicity were evaluated. There were a total of 1241 publications related to lithium toxicity published from 1913 to 2016. Articles (971 or 78.2%) were the most common type, followed by letters (179 or 14.4%) and reviews (61 or 4.9%). The annual publication of articles increased slightly after 1950 and the total number of publications related to lithium toxicity fluctuated with three peaks occurred in 1978, 1985 and 2014. The USA was the predominant country (25.38%), followed by the UK (7.82%), France (6.85%) and Canada (3.55%). Denmark had the highest productivity of publication after standardization by gross domestic product and population size. The average number of citations per article was 9.24, and the h‐index for all publications in the field of lithium toxicity was 46. The highest h‐index value was achieved by the USA (31) followed by the UK (21) and Canada (13). The Lancet was the highest ranked journal with 27 articles, followed by American Journal of Psychiatry with 23 articles. This study provides a bibliometric analysis on the global research trends in lithium toxicity studies during 1913–2015. There has been a progressive increase in the number of publications related to lithium toxicity published in the last decade, and most of the studies related to lithium toxicity arose from the USA and the UK.