Estimation of Serum Levels of Heavy Metals in Patients with Chronic Invasive Fungal Rhinosinusitis Before the COVID-19 Era: A Pilot Study

Objective:Various metals play role in the survival and pathogenesis of the invasive fungal disease. The objectives of this study were to compare the levels of heavy metals in patients with chronic invasive fungal rhinosinusitis (CIFR) and healthy controls, and to analyze their role in disease outcome.Methods:Twenty-three patients (15 with invasive mucormycosis and 8 with invasive aspergillosis, Group 1), and 14 healthy controls (Group 2) were recruited. Blood samples were collected from each group into ion-free tubes and analyzed for serum levels of Nickel (Ni), Copper (Cu), Zinc (Zn), Gallium (Ga), Arsenic (As), Selenium (Se), Rubidium (Rb), Strontium (Sr), Cadmium (Cd), and Lead (Pb). The final outcome of the patients during their hospital stay was categorized clinico-radiologically as improved or worsened, or death.Results:The levels of all metals were higher in Group 1 except for As and Pb. However, the differences in Cu (p=0.0026), Ga (p=0.002), Cd (p=0.0027), and Pb (p=0.0075) levels were significant. Higher levels of Zn (p=0.009), Se (p=0.020), and Rb (p=0.016) were seen in the invasive aspergillosis subgroup. Although Zn (p=0.035), As (p=0.022), and Sr (p=0.002) levels were higher in patients with improved outcome, subgroup analysis showed no differences.Conclusion:The levels of some heavy metals in CIFR significantly differ from those of the general population and also vary with the type of the disease and its outcome. These levels may not have a direct effect on the outcome of the patient, but they do play a role in the pathogenesis of the invading fungus

Comparison between early and delayed facial nerve decompression in traumatic facial nerve paralysis - A retrospective study

ABSTRACT Purpose To study the intraoperative findings in case of early and delayed decompression of facial nerve paralysis and compare their results. Methods Retrospective data analysis of 23 cases of longitudinal temporal bone fracture with House-Brackmann grade V and VI facial nerve paralysis. All cases were thoroughly evaluated and underwent facial nerve decompression through the transmastoid approach. All cases were under regular follow-up till the date of manuscript submission. Results Clinical improvement of the facial nerve function was observed for early vs. delayed facial nerve decompression. In the early decompression group, facial nerve function improved to grade II in eight cases (80%) and grade III in two cases (20%), whereas in the delayed decompression group it improved to grade II in one case (7.70%), grade III in four cases (30.76%), grade IV in seven cases (53.84%), and grade V in one case (7.70%). Conclusions Early decompression of facial nerve provides better results than delayed decompression because it enables early expansion of the nerve

Treatment Patterns and Survival in Locally Advanced or Metastatic Biliary Tract Cancer Using SEER Medicare Data

Background and Aims: Biliary tract cancer (BTC) is a rare, lethal, heterogeneous group of cancers often diagnosed at an advanced stage. While gemcitabine plus cisplatin is the standard of care for first-line treatment of locally advanced or metastatic BTC, no globally accepted standard of care currently exists for second-line treatment of BTC following chemotherapy. However, the treatment landscape is evolving with approvals for therapies targeting actionable mutations. This study aimed to characterize treatment patterns and survival in patients with locally advanced or metastatic BTC. Methods: Patients with advanced or metastatic BTC in the Surveillance, Epidemiology, and End Results Medicare database between 2010 and 2015 (N = 2063) were included; patients with nonprimary BTC were excluded. Patient and clinical characteristics, line and type of therapy, and overall survival of patients were analyzed. Results: Only 45.5% (n = 938) of patients initiated systemic therapy within 90 days of diagnosis. The most common event following diagnosis was initiation of first-line therapy, and the most common event following first-line treatment was death. Median survival ranged from 5.0 months for patients receiving second-line fluoropyrimidine to 9.7 months for patients receiving second-line gemcitabine. Duration of therapy ranged from 0.7 months for patients receiving second-line fluoropyrimidine to 3.7 months for patients receiving first-line gemcitabine plus cisplatin therapy. Conclusion: Overall survival from diagnosis was poor and influenced by age, sex, stage, mobility limitations, comorbidity burden, poverty, and previous cancer. Treatment patterns varied for patients who progressed following first-line therapy, as there was no consensus second-line treatment for locally advanced or metastatic BTC without clinically targetable mutations

Ras Pathway Activation and MEKi Resistance Scores Predict the Efficiency of MEKi and SRCi Combination to Induce Apoptosis in Colorectal Cancer

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. The RAS pathway is activated in more than 55% of CRC and has been targeted for therapeutic intervention with MEK inhibitors. Unfortunately, many patients have de novo resistance, or can develop resistance to this new class of drugs. We have hypothesized that much of this resistance may pass through SRC as a common signal transduction node, and that inhibition of SRC may suppress MEK inhibition resistance mechanisms. CRC tumors of the Consensus Molecular Subtype (CMS) 4, enriched in stem cells, are difficult to successfully treat and have been suggested to evade traditional chemotherapy agents through resistance mechanisms. Here, we evaluate targeting two pathways simultaneously to produce an effective treatment by overcoming resistance. We show that combining Trametinib (MEKi) with Dasatinib (SRCi) provides enhanced cell death in 8 of the 16 tested CRC cell lines compared to treatment with either agent alone. To be able to select sensitive cells, we simultaneously evaluated a validated 18-gene RAS pathway activation signature score along with a 13-gene MEKi resistance signature score, which we hypothesize predict tumor sensitivity to this dual targeted therapy. We found the cell lines that were sensitive to the dual treatment were predominantly CMS4 and had both a high 18-gene and a high 13-gene score, suggesting these cell lines had potential for de novo MEKi sensitivity but were subject to the rapid development of MEKi resistance. The 13-gene score is highly correlated to a score for SRC activation, suggesting resistance is dependent on SRC. Our data show that gene expression signature scores for RAS pathway activation and for MEKi resistance may be useful in determining which CRC tumors will respond to the novel drug combination of MEKi and SRCi

Differential methylation of G-protein coupled receptor signaling genes in gastrointestinal neuroendocrine tumors

Abstract Neuroendocrine tumors (NETs) of the small intestine undergo large chromosomal and methylation changes. The objective of this study was to identify methylation differences in NETs and consider how the differentially methylated genes may impact patient survival. Genome-wide methylation and chromosomal copy number variation (CNV) of NETs from the small intestine and appendix were measured. Tumors were divided into three molecular subtypes according to CNV results: chromosome 18 loss (18LOH), Multiple CNV, and No CNV. Comparison of 18LOH tumors with MultiCNV and NoCNV tumors identified 901 differentially methylated genes. Genes from the G-protein coupled receptor (GPCR) pathways are statistically overrepresented in the differentially methylated genes. One of the highlighted genes from the GPCR pathway is somatostatin (SST), a clinical target for NETs. Patient survival based on low versus high methylation in all samples identified four significant genes (p < 0.05) OR2S2, SMILR, RNU6-653P, and AC010543.1. Within the 18LOH molecular subtype tumors, survival differences were identified in high versus low methylation of 24 genes. The most significant is TRHR (p < 0.01), a GPCR with multiple FDA-approved drugs. By separating NETs into different molecular subtypes based on chromosomal changes, we find that multiple GPCRs and their ligands appear to be regulated through methylation and correlated with survival. These results suggest opportunities for better treatment strategies for NETs based on molecular features