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.     

Neurodegenerative disorder and diffuse brain calcifications due to FARSB mutation in two siblings

Pathogenic mutations in the FARSB gene are associated with neurodevelopmental disorder involving the brain, liver, and lungs. We report genetic analysis of a family including two affected members with this disorder, which revealed a homozygous pathogenic missense variant, FARSB: {"type":"entrez-nucleotide","attrs":{"text":"NM_005687.4","term_id":"743405629","term_text":"NM_005687.4"}}NM_005687.4:c.853G > A:p.E285K in both affected patients. The parents were heterozygous for this variant.     

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.     

Correlation of vitreous chamber depth with ocular biometry in high axial myopia

Purpose:The proportion of axial length (AL) occupied by vitreous chamber depth (VCD), or VCD:AL, consistently correlates to ocular biometry in the general population. Relation of VCD:AL to ocular biometry in high myopia is not known. The purpose of this study is to evaluate the relation of VCD and VCD:AL to ocular biometry of highly myopic eyes.Methods:This was a cross-sectional retrospective study of records of 214 myopic eyes (<−1 D SE, aged 20–40 years) attending the refractive surgery services. High axial myopia was defined as AL >26.5 mm. Eyes with posterior staphyloma and myopic maculopathy were excluded. Records were assessed for measurements of AL, central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), white to white diameter (WTW), and vitreous chamber depth (VCD). Groups were formed based on increasing AL, while the sum of CCT, ACD, and LT was recorded as anterior segment depth (AS). The main outcome measure was the correlation of VCD and VCD:AL to ocular biometry. A comparison was also performed based on of degree of axial myopia.Results:Mean age of the patients was 27.0 ± 5.2 years. VCD showed a very strong correlation with AL (R = 0.98, P < 0.001) but did not correlate to any anterior parameter. VCD:AL showed moderate negative relation with AS (R = −0.43, P < 0.001) and ACD (R = −0.3, P < 0.001), while it had a weakly negative relation with LT (R = −0.18, P = 0.006). VCD:AL showed strong negative relation (R > ~0.7) with AS in all individual groups of AL. Among anterior parameters, WTW showed the most consistent relation with ocular biometry.Conclusion:VCD:AL is a better correlate of ocular biometry in high myopia as compared to VCD. However, the correlation is weaker than that noted by previous studies done on the general population. Longitudinal studies of VCD:AL in the younger age group is recommended.     

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.