Real world results of locally advanced and metastatic lung cancer patients treated with platinum doublet chemotherapy in first line: Moroccan cohort.

BACKGROUND: Doublet platin-chemotherapy was the old standard treatment for different histology types of advanced and metastatic lung cancer (LC) and is still an option for patients who are not eligible for immune checkpoint inhibitors. However, in low- and middle-income countries, chemotherapy, either in monotherapy or in combination with platinum, is still the only accessible option in public institutions. The efficacy of different platin-based chemotherapy in patients with LC who are treatment-naïve is unknown. METHODS: In this retrospective study, we selected patients with advanced and metastatic (IIIB-IVB) non-squamous non-small cell LC (NSCLC), squamous NSCLC, and lung neuroendocrine tumours (small cell LC (SCLC), large cell neuroendocrine, and atypical carcinoid) aged beyond 18 years who received first-line chemotherapy (docetaxel, gemcitabine, etoposide, paclitaxel, pemetrexed, and vinorelbine) combined with platinum between January 1, 2013, and December 31, 2022. Within the population with non-squamous NSCLC, squamous NSCLC, and neuroendocrine tumours, progression-free survival (PFS) and overall survival (OS) were the primary assessed endpoints. Hematologic safety was the secondary endpoint. RESULTS: Overall, 611 patients were included. In the group of patients with non-squamous NSCLC (n = 390), there was no statistical difference between subgroups of patients who received first-line platin-chemotherapy. The median PFS was 182 (95 % confidence interval [CI], 167-208) days (hazard ratio for progression: NR [Not Reached]; p = 0.37), and the median OS was 446 (95 % CI, 405-559) days (hazard ratio for death: 1.31; 95 % CI, 0.94 - 1.82; p = 0.1). In the group of patients with squamous NSCLC (n = 149), we note the absence of statistical significance between subgroups of patients who received platin-based chemotherapy. The median PFS was 195 (95 % CI, 142-238; hazard ratio for progression: 1.21, 95 % CI, 0.29-5.02; p = 0.27), while the median OS was 428 (95 % CI, 324-940) days (hazard ratio for death: 1.76; 95 % CI, 0.93 to 3.3; p = 0.32). The absence of significance has been noticed in the neuroendocrine subgroup of patients who received first etoposide-platinum, vinorelbine-platinum, or paclitaxel-platinum (n = 72). The median PFS was 216 (95 % CI, 193-277) days; hazard ratio for progression: 1.74, 95 % CI, 0.41-7.27; p = 0.69, while the median OS was 273 (95 % CI, 241-459) days (hazard ratio for death: 2.95; 95 % CI, 0.4-21.7; p = 0.51). Grade 3-4 neutropenia grade was the predominant adverse event associated with chemotherapy in almost 11 % of patients. CONCLUSION: Moving forward, treatment strategies must be refined for patients, with an emphasis on increasing the number of patients who can benefit from emergent approaches in order to guarantee a wider, deeper, and longer-lasting outcome.

The Impact of Local Control on Overall Survival after Y-90 Selective Internal Radiotherapy of Liver Metastases in Oligometastatic Cancer: A Retrospective Analysis.

Y-90 Selective Internal Radiotherapy (SIRT) is an ablative therapy used for inoperable liver metastasis. The purpose of this investigation was to examine the impact of local control after SIRT on overall survival (OS) in oligometastatic patients. A retrospective, single-institution study identified oligometastatic patients with ≤5 non-intracranial metastases receiving unilateral or bilateral lobar Y-90 SIRT from 2009 to 2021. The primary endpoint was OS defined from Y-90 SIRT completion to the date of death or last follow-up. Local failure was classified as a progressive disease at the target lesion(s) by RECIST v1.1 criteria starting at 3 months after SIRT. With a median follow-up of 15.7 months, 33 patients were identified who had a total of 79 oligometastatic lesions treated with SIRT, with the majority histology of colorectal adenocarcinoma (n = 22). In total, 94% of patients completed the Y-90 lobectomy. Of the 79 individual lesions treated, 22 (27.8%) failed. Thirteen patients received salvage liver-directed therapy following intrahepatic failure; ten received repeat SIRT. Median OS (mOS) was 20.1 months, and 12-month OS was 68.2%. Intralesional failure was associated with worse 1 y OS (52.3% vs. 86.2%, p = 0.004). These results suggest that intralesional failure following Y-90 may be associated with inferior OS, emphasizing the importance of disease control in low-metastatic-burden patients.

Mercury in the Southwestern Atlantic reef-building coral Montastraea cavernosa (Cnidaria, Scleractinia).

Coastal ecosystems, such as coral reefs, are particularly vulnerable to mercury contamination due to direct contact with terrestrial sources. Here, we evaluated, for the first time, the concentration of mercury in coral reefs in the Southwestern Atlantic using the amphi-atlantic scleractinian coral Montastraea cavernosa. Sampling was realized over an extension of 200 km along different coral reefs. Our data show mercury values ranging from 0.01 to 0.27 mg kg-1 in the tissue and 0.001 to 0.06 mg kg-1 in the skeleton and higher values when compared to coral worldwide. The concentration of mercury in the tissue from Todos os Santos Bay was higher than in open sea regions but also higher compared to other coral reefs of the world, while the skeleton concentration did not indicate any differences when compared to the open sea regions. The data presented is of concern as we consider the importance of coral reefs and should be used in future environmental management planning.

Metabolic remodeling by RNA polymerase gene mutations is associated with reduced ß-lactam susceptibility in oxacillin-susceptible MRSA.

The emergence of oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA) has imposed further challenges to the clinical management of MRSA infections. When exposed to ß-lactam antibiotics, these strains can easily acquire reduced ß-lactam susceptibility through chromosomal mutations, including those in RNA polymerase (RNAP) genes such as rpoBC, which may then lead to treatment failure. Despite the increasing prevalence of such strains and the apparent challenges they pose for diagnosis and treatment, there is limited information available on the actual mechanisms underlying such chromosomal mutation-related transitions to reduced ß-lactam susceptibility, as it does not directly associate with the expression of mecA. This study investigated the cellular physiology and metabolism of six missense mutants with reduced oxacillin susceptibility, each carrying respective mutations on RpoBH929P, RpoBQ645H, RpoCG950R, RpoCG498D, RpiAA64E, and FruBA211E, using capillary electrophoresis-mass spectrometry-based metabolomics analysis. Our results showed that rpoBC mutations caused RNAP transcription dysfunction, leading to an intracellular accumulation of ribonucleotides. These mutations also led to the accumulation of UDP-Glc/Gal and UDP-GlcNAc, which are precursors of UTP-associated peptidoglycan and wall teichoic acid. Excessive amounts of building blocks then contributed to the cell wall thickening of mutant strains, as observed in transmission electron microscopy, and ultimately resulted in decreased susceptibility to ß-lactam in OS-MRSA. IMPORTANCE: The emergence of oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA) strains has created new challenges for treating MRSA infections. These strains can become resistant to ß-lactam antibiotics through chromosomal mutations, including those in the RNA polymerase (RNAP) genes such as rpoBC, leading to treatment failure. This study investigated the mechanisms underlying reduced ß-lactam susceptibility in four rpoBC mutants of OS-MRSA. The results showed that rpoBC mutations caused RNAP transcription dysfunction, leading to an intracellular accumulation of ribonucleotides and precursors of peptidoglycan as well as wall teichoic acid. This, in turn, caused thickening of the cell wall and ultimately resulted in decreased susceptibility to ß-lactam in OS-MRSA. These findings provide insights into the mechanisms of antibiotic resistance in OS-MRSA and highlight the importance of continued research in developing effective treatments to combat antibiotic resistance.

Long-term outcomes of the BalMedic bovine pericardial bioprosthetic valve in female patients ≤50 years: a multicenter retrospective study.

Background: A bioprosthetic valve is recommended for women of childbearing age who require cardiac valve replacement in order to minimize the risk of blood clot formation. However, it should be noted that compared to mechanical valves, bioprosthetic valves have a shorter lifespan and a higher likelihood of requiring reoperation during follow-up. To assess the long-term postoperative results, including the incidence of structural valve deterioration (SVD) and other clinical outcomes, in female patients aged 50 years and younger who underwent BalMedic bovine pericardial bioprosthetic valve replacement, a multicenter retrospective study was implemented in China. Methods: Between 2004 and 2015, a cohort of 86 female patients across three medical centers underwent the implantation of 97 bioprosthetic valves. The primary outcome measure was overall survival (OS), while the secondary outcome measures were preliminary evidence of reoperation, SVD incidence, and bioprosthetic valve-related complications. Results: In this cohort study, 21 patients (24.4%, 21/86) died, while 37 patients (43.0%, 37/86) underwent a second valve replacement. The OS rates at 5 and 10 years were 97.56% and 71.93%, respectively. Additionally, the reoperation-free rates at 5 and 10 years were 92.83% and 80.68%, respectively. Similarly, the rates of freedom from SVD at 5 and 10 years were 95.65% and 51.82%, respectively, and the average duration of bioprosthetic valve replacement in our study was 9.34±3.31 years. Conclusions: Despite the recruitment of younger female patients of child-bearing age in our cohort, the OS, reoperation-free survival, and SVD-free rates of the BalMedic bovine pericardial bioprosthetic valve were not inferior to those of the other age groups in the study or those reported in the literature.

Efficacy of cytoreductive surgery for metastatic upper tract urothelial carcinoma: a Surveillance, Epidemiology and End Results (SEER) study of 508 patients.

Background: Cisplatin-based combination chemotherapy alone is currently considered the standard of care for patients with metastatic upper tract urothelial carcinoma (mUTUC). However, less research has been done on the efficacy of other combinations. In this study, we explored the role of cytoreductive surgery in patients with mUTUC receiving different types of systemic therapy. Methods: Data from 9,436 anonymized records were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2008-2018. Of these, 508 individuals received systemic therapy subsequent to being diagnosed with mUTUC. These patients had all been treated with systemic therapies such as chemotherapy and/or radiotherapy. Patients were stratified into either a non-surgical or surgical group based on cytoreductive surgery status before systemic therapeutics commenced. Kaplan-Meier curves were used to compare overall survival (OS) and cancer-specific survival (CSS). Cox's proportional hazard models were then used to analyze prognostic factors related to OS and CSS. Results: Of the 508 cases, 36.8% (n=187) had received cytoreductive surgery with systemic treatments. The remaining 63.2% (n=321) received either chemotherapy and/or radiotherapy alone. Kaplan-Meier curves showed that 11.6% had 3-year OS [95% confidential interval (CI): 7.1-17.3] for cytoreductive surgery with systemic treatment and 4.9% (95% CI: 2.7-8.0) for systemic treatment alone (P=0.001). The 3-year CSS was 14.9% for cytoreductive surgery plus systemic treatment (95% CI: 9.4-21.7%) and 6.0% (95% CI: 3.4-9.8%) for systemic treatments alone (P=0.003). Under multivariate regression analysis, primary ureter site OS had a hazard ratio (HR) of 0.74 (95% CI: 0.58-0.95, P=0.02) and a CSS HR of 0.72 (95% CI: 0.56-0.94, P=0.01). The cytoreductive surgery OS HR was 0.79 (95% CI: 0.65-0.95, P=0.02) and the CSS HR was 0.75 (95% CI: 0.61-0.92, P=0.006). Additionally, chemotherapy had an OS HR of 0.46 (95% CI: 0.33-0.0.65, P<0.001) and a CSS HR of 0.44 (95% CI: 0.31-0.63, P<0.001). Bones and liver metastases were also indicative of poorer prognosis. Validation was conducted through subgroup analysis which suggested cytoreductive surgery was effective only for patients who received chemotherapy or combined chemo-radiotherapy but not for radiotherapy alone. Conclusions: Cytoreductive surgery provided significantly increased OS and CSS for mUTUC patients who received chemotherapy or combined chemo-radiotherapy in this study. In addition, the primary tumor and metastatic sites were shown to be related to improved patient survival although this was a small and relatively homogeneous cohort of study, sample therefore, further research is required.

Genetic Profiling and Survival Outcomes in Romanian Colorectal Cancer Patients.

BACKGROUND: The increasing incidence of colorectal cancer is one of the most frequently addressed medical topics worldwide. It represents the third most commonly diagnosed cancer in both men and women globally, with significant implications for public health. Mortality for this type of malignancy remains high, second only to lung cancer. Given their clinical relevance, the identification and understanding of KRAS and BRAF mutations have become crucial components of personalized medicine approaches in colorectal cancer. Hence, our desire is to carry out a research that analyzes the impact of these mutations in terms of survival and mortality on patients diagnosed with colorectal cancer. METHODS: We conducted a retrospective study spanning from 2018 to 2022, which involved 118 patients diagnosed with colorectal cancer. The patients were selected from the databases of the Oradea County Emergency Clinical Hospital and Pelican Oradea Hospital. Genetic testing was performed at the "Resident Laboratory" clinic. Subsequently, patients were divided into two groups of equal size based on the presence or absence of mutations. RESULTS: The survival rate one year after the diagnosis of colorectal cancer is 84.74% (N=50/59) for the mutant group versus 67.96% (N=40/59) for the wild-type group. The survival rate at five years from the diagnosis of colorectal cancer is 25.93% (N=15/59) for patients with wild-type tumors compared to 33.54% (N=20/59) for patients with tumors with mutant status (p=0.483, HR=1.153, CI 95% 0.7661-1.735). The five-year survival rate, depending on the mutation present, highlights the fact that the average overall survival for those with the KRAS mutation is 38.6 months (CI 95% 35.22-41.97) and for those with the BRAF mutation is 8.3 months (CI 95% 5.42-11.17) (p=0.039). The mortality rate for mutant KRAS is 44.89% (N=22/50), while for those with mutant BRAF, it is 100% (N=6/6). CONCLUSIONS: We observed no statistically significant difference in overall survival rate and disease-free interval between the two studied groups, but the overall survival was better for those with mutations present (38.64 months versus 31.07 months for wild-type tumors). The mortality rate is higher among tumors with wild-type status (p=0.005), in the first year after the diagnosis of colorectal cancer. The BRAF mutation confers a much worse prognosis than the KRAS mutation, from both the survival analysis and the mortality rate.

Values of a novel comprehensive prognostic nutritional index (FIDA) in the prognosis of non-small cell lung cancer.

Background: This study focuses on determining the prognostic and predictive value of the comprehensive prognostic nutrition index (FIDA) in individuals undergoing treatment for Non-Small-Cell Lung Carcinoma (NSCLC). Methods: This retrospective analysis encompassed 474 of NSCLC patients treated from January 2010 through December 2019. Employing the Lasso-COX regression approach, eight blood parameters were identified as significant prognostic indicators. These parameters contributed to the formulation of the comprehensive prognostic nutrition index FIDA. Utilizing X-tile software, the patient cohort was categorized into either a high or low FIDA group based on an established optimal threshold. The cohort was then randomly segmented into a training set and a validation set using SPSS software. Subsequent steps involved conducting univariate and multivariate regression analyze to develop a prognostic nomogram. The effectiveness of this nomogram was evaluated by calculating the AUC. Results: Analysis of survival curves for both the training and validation sets revealed a poorer prognosis in the high FIDA group compared to the low FIDA group. This trend persisted across various subgroups, including gender, age, and smoking history, with a statistical significance (p<0.05). Time-dependent ROC and diagnostic ROC analyses affirmed that FIDA serves as an effective diagnostic and prognostic marker in NSCLC. Moreover, Cox regression multivariate analysis established FIDA as an independent prognostic factor for NSCLC. The prognostic nomogram, integrating FIDA and clinical data, demonstrated substantial prognostic utility and outperformed the traditional TNM staging systemin predicting overall survival (OS). Conclusion: FIDA emerges as a dependable predictor of outcomes for patients with NSCLC. It offers a practical, cost-effective tool for prognostication in regular clinical applications.

Advancing lung adenocarcinoma prognosis and immunotherapy prediction with a multi-omics consensus machine learning approach.

Lung adenocarcinoma (LUAD) is a tumour characterized by high tumour heterogeneity. Although there are numerous prognostic and immunotherapeutic options available for LUAD, there is a dearth of precise, individualized treatment plans. We integrated mRNA, lncRNA, microRNA, methylation and mutation data from the TCGA database for LUAD. Utilizing ten clustering algorithms, we identified stable multi-omics consensus clusters (MOCs). These data were then amalgamated with ten machine learning approaches to develop a robust model capable of reliably identifying patient prognosis and predicting immunotherapy outcomes. Through ten clustering algorithms, two prognostically relevant MOCs were identified, with MOC2 showing more favourable outcomes. We subsequently constructed a MOCs-associated machine learning model (MOCM) based on eight MOCs-specific hub genes. Patients characterized by a lower MOCM score exhibited better overall survival and responses to immunotherapy. These findings were consistent across multiple datasets, and compared to many previously published LUAD biomarkers, our MOCM score demonstrated superior predictive performance. Notably, the low MOCM group was more inclined towards 'hot' tumours, characterized by higher levels of immune cell infiltration. Intriguingly, a significant positive correlation between GJB3 and the MOCM score (R = 0.77, p < 0.01) was discovered. Further experiments confirmed that GJB3 significantly enhances LUAD proliferation, invasion and migration, indicating its potential as a key target for LUAD treatment. Our developed MOCM score accurately predicts the prognosis of LUAD patients and identifies potential beneficiaries of immunotherapy, offering broad clinical applicability.

Nil per os in the management of oropharyngeal dysphagia-exploring the unintended consequences.

Nil per os (NPO), also referred to as Nil by Mouth (NBM), is a health-related intervention of withholding food and fluids. When implemented in the context of a person with dysphagia, NPO aims to mitigate risks of aspiration. However, evidence demonstrating that NPO is beneficial as an intervention for people with dysphagia is lacking. This paper explores the theoretical and empirical evidence relating to the potential benefits and adverse effects of NPO and asserts that NPO is not a benign intervention. This paper argues for applying an ethics framework when making decisions relating to the use of NPO as an intervention for dysphagia, in particular addressing informed consent and a person's right to self-determination.

A novel inflammatory nutrient index for predicting survival outcomes in patients with non-small cell lung cancer.

Background: Lung cancer is one of the most common contributors to cancer-related deaths worldwide. This study aimed to develop a new blood index on the basis of the patient's systemic inflammation and nutritional status, which can be used to predict the prognosis of patients with non-small cell lung cancer (NSCLC). Methods: Pre-treatment blood markers were analyzed in 556 NSCLC patients from 2010 to 2019. A least absolute shrinkage and selection operator (LASSO) method was used to select indicators to establish a new integrated biomarker (PNAGR). Kaplan-Meier survival curves were used to assess the prognostic impact of platelet-to-lymphocyte ratio (PLR), albumin (ALB), and the PNAGR. The prognostic value was verified using univariate and multivariate Cox analyses. Results: We used four biomarkers including PLR, ALB, 1/albumin-to-globulin ratio (1/AGR), and neutrophil/albumin-to-globulin ratio (N/AGR) were used to screen for the PNAGR using LASSO. Patients with high PNAGR demonstrated lower overall survival (OS) compared to those with low PNAGR. In both univariate and multivariate analyses, PNAGR was revealed as an independent prognostic factor for OS. The predictive power of PNAGR [area under the curve (AUC): 0.753] was higher than that of the metrics alone. Conclusions: PNAGR is a novel and effective clinical prognostic tool with good clinical predictive value for NSCLC patients.

MFAP2 induces epithelial-mesenchymal transformation of osteosarcoma cells by activating the Notch1 pathway.

Background: Osteosarcoma (OS) is a malignancy originating from mesenchymal tissue. Microfibril-associated protein 2 (MFAP2) plays a crucial role in cancer, notably promoting epithelial-mesenchymal transition (EMT). However, its involvement in OS remains unexplored. Methods: MFAP2 was silenced in U2OS cells using shRNA targeting MFAP2 (sh-MFAP2) and validated by quantitative real-time polymerase chain reaction (qRT-PCR). We extracted gene chip data of MFAP2 from multiple databases (GSE28424, GSE42572, and GSE126209). Correlation analyses between MFAP2 and the Notch1 pathway identified through the gene set variation analysis (GSVA) enrichment analysis were conducted using the Pearson correlation method. Cellular behaviors (viability, migration, and invasion) were assessed via the Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays. EMT markers (N-cadherin, vimentin, and ß-catenin) and Notch1 levels were examined by western blotting and qRT-PCR. Cell morphology was observed microscopically to evaluate EMT. Finally, the role of MFAP2 in OS was validated through a xenograft tumor model. Results: OS cell lines exhibited higher MFAP2 mRNA expression than normal osteoblasts. MFAP2 knockdown in U2OS cells significantly reduced viability, migration, and invasion, along with downregulation of N-cadherin and vimentin, as well as upregulation of ß-catenin. MFAP2 significantly correlated with the Notch1 pathway in OS and its knockdown inhibited Notch1 protein expression. Furthermore, Notch1 activation reversed the inhibitory effects of MFAP2 knockdown on the malignant characteristic of U2OS cells. Additionally, MFAP2 knockdown inhibited tumor growth, expression levels of EMT markers, and Notch1 expression in OS tumor tissues. Conclusions: Our study revealed that MFAP2 was an upstream regulator of the Notch1 signaling pathway to promote EMT in OS. These findings suggested MFAP2 as a potential OS therapy target.

Os Subepicondylare Mediale in the Elbow: A Radiographic Case Report of a Sesamoid Bone.

Sesamoid and accessory bones are small, oval-shaped structures that develop within tendons that pass over bony prominences. Although rare, accessory bones in the elbow region hold clinical significance because they can cause diagnostic uncertainty. We present the case of a 47-year-old previously healthy female patient who presented with left elbow pain and was discovered to have a sesamoid bone distal to the medial epicondyle of the humerus. On examination, the patient's left elbow was tender, but her range of motion was in normal range. Plain radiographs identified a small, oval-shaped bony fragment; further radiographic investigations were conducted. Computed tomography and ultrasound were performed to rule out diagnostic uncertainties. A diagnosis of os subepicondylare mediale, a rare sesamoid bone, was established through a thorough investigation of the well-circumscribed structure in accordance with the most current literature.

Highlights of ophthalmological manifestations in newly diagnosed acute leukemia: a correlation with hematological parameters.

Acute leukemia is a hematological malignancy affecting different organ systems including the eye and orbit through direct infiltration of tissues or secondary to hematological abnormalities. Ophthalmological manifestations in acute leukemia are variable ranging from asymptomatic presentation to serious manifestations that can alter the disease course and treatment. The purpose of this study is to detect the incidence of different ophthalmological manifestations in newly diagnosed acute leukemia patients and to assess the relationship between ocular findings and hematological characteristics and the sequel of these neoplasms. A cross-sectional study with analytical components was conducted on 222 newly diagnosed acute myeloid and acute lymphoblastic leukemia patients who presented at Oncology Center Mansoura University (OCMU) between January 2022 and February 2023. All patients underwent a complete ophthalmic evaluation at Mansoura Ophthalmology Center (MOC). The mean age was 43.45 ± 17.35 years (range, 17-85), and M/F was 137 (61.7%)/85 (38.3%). One-hundred and forty-four (64.9%) had acute myeloid leukemia (AML), and 78 (35.1%) had acute lymphoblastic leukemia (ALL). Ophthalmic manifestations were detected in 96 patients (43.2%). Among them, 4 (1.8%) had poor visual acuity. Retinal hemorrhage (19.8%) and Roth spots (17.1%) were the most common ocular manifestations. Other ophthalmological manifestations observed were orbital involvement (3.2%), ocular motility issues (1.4%), subconjunctival hemorrhage (5.9%), conjunctival chemosis (0.9%),lid swelling (4.1%), lid ecchymosis (3.2%), lagophthalmos (0.5%), lid ptosis (1.8%), retinal venous congestion & tortuosity (4.1%), preretinal hemorrhage (3.2%), vitreous hemorrhage (3.2%), macular affection (2.3%), retinal infiltration (1.8%), exudative retinal detachment (ERD) (1.8%), cotton-wool spots (0.9%), retinal vein occlusion (0.5%), papilledema (2.8%), optic disc infiltration (1.8%), disc pallor (1.8%).AML patients were significantly associated with a higher frequency of ocular affection, retinal hemorrhages, and Roth spots (P 0.028, 0.003, and 0.046, respectively) compared to ALL patients. Retinal hemorrhage was statistically significantly associated with anemia (P 0.021). Ophthalmological manifestations of acute leukemia are heterogeneous; they can be detected at initial presentations or relapse. Some manifestations are asymptomatic, others can affect visual acuity or even alter the disease course. Cooperation between ophthalmologists and haemato-oncologists is crucial for recognizing ocular involvement and disease management.

METTL3 promotes the progression of osteosarcoma through the N6-methyladenosine modification of MCAM via IGF2BP1.

BACKGROUND: The molecular mechanisms of osteosarcoma (OS) are complex. In this study, we focused on the functions of melanoma cell adhesion molecule (MCAM), methyltransferase 3 (METTL3) and insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) in OS development. METHODS: qRT-PCR assay and western blot assay were performed to determine mRNA and protein expression of MCAM, METTL3, IGF2BP1 and YY1. MTT assay and colony formation assay were conducted to assess cell proliferation. Cell apoptosis, invasion and migration were evaluated by flow cytometry analysis, transwell assay and wound-healing assay, respectively. Methylated RNA Immunoprecipitation (MeRIP), dual-luciferase reporter, Co-IP, RIP and ChIP assays were performed to analyze the relationships of MCAM, METTL3, IGF2BP1 and YY1. The functions of METTL3 and MCAM in tumor growth were explored through in vivo experiments. RESULTS: MCAM was upregulated in OS, and MCAM overexpression promoted OS cell growth, invasion and migration and inhibited apoptosis. METTL3 and IGF2BP1 were demonstrated to mediate the m6A methylation of MCAM. Functionally, METTL3 or IGF2BP1 silencing inhibited OS cell progression, while MCAM overexpression ameliorated the effects. Transcription factor YY1 promoted the transcription level of METTL3 and regulated METTL3 expression in OS cells. Additionally, METTL3 deficiency suppressed tumor growth in vivo, while MCAM overexpression abated the effect. CONCLUSION: YY1/METTL3/IGF2BP1/MCAM axis aggravated OS development, which might provide novel therapy targets for OS.

Preoperative Low Creatine Kinase as a Poor Prognostic Factor in Patients with Colorectal Cancer.

PURPOSE: This study aimed to evaluate the clinicopathological and prognostic significance of preoperative serum creatine kinase (CK) levels in colorectal cancer. METHODS: This study analyzed 1169 patients with colorectal cancer at stages 0 (n = 35), I (n = 301), II (n = 456), III (n = 339), and IV (n = 38). The CK cut-off value was 52 U/L to predict recurrence based on receiver operative characteristics curve. Clinicopathological factors were compared between the low (< 52 U/L) and high CK groups (≥ 52 U/L). The multivariate analysis evaluated relapse-free survival (RFS) and overall survival (OS) following CK status. RESULTS: The female sex, elderly age (≥ 75), deep tumor (pT4), and carcinoembryonic antigen (+) were independently associated with low CK status. The recurrent rate was significantly higher in the low CK group than in the high CK group (19.1% vs. 11.7%, p < 0.001). Elderly age, pT4, pN (+), preoperative carbohydrate antigen (CA) 19-9 (+), and low CK status were independent risk factors for RFS. Elderly age, pT4, pN (+), preoperative CA19-9 (+), and low CK status were independent risk factors for OS. CONCLUSION: Preoperative low CK status was associated with deep tumors and was a poor prognostic factor in patients with colorectal cancer.

Prognostic value of tumor-stroma ratio in clear cell renal cell carcinoma after surgery.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common urological tumors, and its incidence is increasing year by year. Tumor stroma ratio (TSR) can reflect the amount of stromal component around tumor cells, and can independently predict the prognosis of tumor. This study aims to evaluate the prognostic value of TSR in ccRCC patients. Methods: From January 2010 to December 2015, clinical and histopathological data of patients with ccRCC patients who underwent surgical operation were collected. Using TSR (50%) as the cut-off value, the patients were divided into low-TSR group (<50%) and high-TSR group (≥50%). The clinicopathological characteristics and survival status of patients were compared between the two groups. Univariate and multivariate analyses were used to identify the prognostic factors for overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS). Results: The mean age of 569 patients was 56.84±12.76 years old. There were 401 males and 168 females. According to the TSR, patients were divided into low-TSR group (n=333, 58.5%) and high-TSR group (n=236, 41.5%). The median follow-up time was 67.0 months (interquartile range, 33.0-72.0 months). The 5-year OS, CSS and MFS were 91.2%, 94.6% and 91.0%, respectively. The 5-year OS, CSS and MFS were 84.2%,89.7% and 82.7% in the high-TSR group and 96.1%, 98.0% and 96.0% in the low-TSR group (P<0.05). Multivariate analysis showed that age >60 years [hazard ratio (HR) =2.455, 95% confidence interval (CI): 1.292-4.668, P=0.006), tumor grade (HR =6.580, 95% CI: 3.276-13.216, P<0.001) and TSR (HR =2.611, 95% CI: 1.265-5.387, P=0.009) were independent prognostic factors for OS. Multivariate analysis showed that tumor stage (HR =3.213, 95% CI: 1.437-7.184, P=0.004), tumor grade (HR =6.102, 95% CI: 2.664-13.976, P<0.001) and TSR (HR =2.653, 95% CI: 1.063-6.621, P=0.03) were independent prognostic factors for CSS. Multivariate analysis showed that tumor stage (HR =4.805, 95% CI: 2.677-8.624, P<0.001), tumor grade (HR =6.423, 95% CI: 3.432-12.020, P<0.001), hemorrhage (HR =0.514, 95% CI: 0.265-0.996, P=0.049) and TSR (HR =2.370, 95% CI: 1.264-4.443, P=0.007) were independent prognostic factors for MFS. Conclusions: TSR is a new independent prognostic risk factor for ccRCC patients. The assessment of TSR is simple and cost-effective, and it is a useful supplement added to the pathological evaluation system.

Lymphocytic Host Response and other Prognostic Factors in Early Stage Squamous Cell Carcinoma of Tongue: Retrospective Analysis from a Tertiary Cancer Center.

Aswin Anapathoor NagarajanIntroduction The tongue is the most common site of malignancy in the oral cavity, and squamous cell carcinoma is the commonest histology. The prognosis remains unfavorable despite treatment, resulting in higher mortality rates. Early stage carcinoma of the tongue is a distinct entity and is primarily treated with either surgery or radiotherapy. Various factors have been implicated in the prognosis of early stage tongue carcinomas. The main objective of this study is to access whether the lymphocytic host response (LHR) and other prognostic factors influence the survival. Patients and Methods The data of 129 patients with Stage I and Stage II (T1-2, N0) tongue cancer treated in our institute from January 2012 to December 2016 were retrospectively abstracted from the hospital case records. The various clinical and pathological factors were recorded. The Kaplan-Meier model was used for survival analysis. The disease-free survival (DFS) and the overall survival (OS) with respect to stage and LHR were calculated. Results On multivariate analysis, site of lesion, comorbidities, habits, grade of the tumor, perineural infiltration (PNI) did not influence the survival. The main factor which was found to be significant in DFS was LHR. The DFS was better for the patients who had lymphocytic infiltration of ≥ 70% (strong LHR) when compared with <70%(weak LHR) ( p = 0.037). The OS with respect to stage ( p = 0.608) and LHR ( p = 0.164) was not found to be statistically significant. Conclusion The patients with weak LHR had less DFS when compared with patients with strong LHR. Larger studies are needed to evaluate whether adding adjuvant therapy may benefit the patients with weak LHR in early stage tongue cancer.

Enfortumab vedotin-related cutaneous toxicity correlates with overall survival in patients with urothelial cancer: a retrospective experience.

Introduction: Enfortumab vedotin (EV) is an antibody drug conjugate approved for advanced urothelial cancer, consisting of a monomethyl auristatin E payload linked to a human monoclonal antibody targeting nectin-4. No validated biomarker predictive of or correlated with response exists for EV. Cutaneous toxicity is among the most common EV-related toxicities and typically emerges in early cycles. This retrospective experience of patients with urothelial cancer treated with EV monotherapy evaluated whether EV-related cutaneous toxicity correlated with improved outcomes including progression-free (PFS) and overall (OS) survival and overall response rate (ORR). Patients and methods: Patients treated with EV monotherapy at Johns Hopkins were identified, and baseline characteristics, treatment, and toxicity details were extracted through chart review. Univariable Cox hazard ratios (HRs) were calculated for assessing the effect of baseline patient characteristics and cutaneous toxicity in PFS and OS. Based on the univariable analysis and known risk factors, all subsequent analyses were adjusted for: Eastern Cooperative Oncology Group performance status, visceral metastases at baseline, gender as well as EV dose, and weight to account for dosing differences. Multivariable Cox proportional HRs were used for comparing PFS and OS between patients with and without cutaneous toxicity, assessing toxicity and EV dose as a time-dependent variables. Adjusted p-values were calculated to compare ORR and disease control rate (DCR) between groups using the Poisson regression model. Results: Of the 78 patients analyzed, 42 (53.8%) experienced EV-related cutaneous toxicity that appeared early during treatment (median time to occurrence 0.5 months from EV initiation). Cutaneous toxicity correlated with significantly improved OS [HR, 0.48; 95% confidence interval (CI), 0.25, 0.9; P = 0.0235], ORR (68.3% vs. 20.7%, P = 0.0033) and DCR (82.9% vs. 48.3%, P = 0.0122). Median PFS was numerically longer in the cutaneous toxicity group (6.3 vs. 1.7 months), although no significance was achieved in the multivariable analysis (HR, 0.62; 95% CI: 0.35, 0.108; P = 0.0925). Conclusion: In this retrospective study, EV-related cutaneous toxicity was associated with improved patient outcomes. Confirming this observation and understanding its mechanism could lead to discovery of a new clinical biomarker of EV response that can emerge in the first cycle.