Anticipated time to seek medical advice for possible lung cancer symptoms and barriers to timely presentation in Palestine: a national cross-sectional study.

BACKGROUND: Lung cancer (LC) has poor survival outcomes mainly due to diagnosis at late stages. This study explored the anticipated time to seek medical advice for possible LC symptoms and barriers to early presentation in Palestine. METHODS: This cross-sectional study recruited adult participants from hospitals, primary healthcare centers, and public spaces of 11 governorates using convenience sampling. A modified, translated-into-Arabic version of the validated LC awareness measure was used to assess LC symptom awareness, the time needed to seek medical advice and barriers to early presentation. RESULTS: A total of 4762 participants were included. The proportion that would immediately seek medical advice for possible LC symptoms varied according to the symptoms' nature. For respiratory symptoms, this ranged from 15.0% for 'painful cough' to 37.0% for 'coughing up blood'. For non-respiratory symptoms, this ranged from '4.2% for 'unexplained loss of appetite' to 13.8% for 'changes in the shape of fingers or nails'. Participants with good LC symptom awareness were more likely to seek medical advice within a week of recognizing most LC symptoms. About 13.0% would delay their visit to see a doctor after recognizing an LC symptom. The most reported barriers were emotional with 'disliking the visit to healthcare facilities' (59.8%) as the leading barrier. CONCLUSION: LC respiratory symptoms were more likely to prompt early seeking of medical advice. Good LC symptom awareness was associated with a higher likelihood of help-seeking within a week. Educational interventions are needed to promote LC awareness and address the perceived barriers to early presentation in low-resource settings, such as Palestine.

A Pseudo-near isogenic F2 population strategy for rapid QTL cloning.

Near isogenic F2 (NIF2) population frequently developed by conventional backcross has dramatically contributed to QTL identification in plants. Developing such a NIF2 population is time-consuming. Thus, it is urgent to rapidly produce a NIF2 population for QTL cloning. Here, we proposed a rapid QTL cloning strategy by generating a Pseudo-near isogenic F2 population (Pseudo-NIF2), which segregates at the target QTL but is fixed at other QTLs for the target trait. Nineteen QTLs for GL, GW, and TGW were detected in the F2 population from the cross between Zhenshan 97 and Egy316. To verify the efficiency of Pseudo-NIF2 in QTL quick cloning, the novel moderate QTL qGL10.1 which explained 9.1% and 5.6% of grain length variation in F2 and F2:3 populations was taken as an example. An F2 plant (F2-120), which segregated at qGL10.1 but fixed at other 8 QTLs for grain length, was screened to generate a Pseudo-NIF2 population by selfing cross. In the Pseudo-NIF2 population, the segregation ratio of plants with long grains to short grains fits 3:1, indicating that one gene controlled the variation of grain length. Based on the Pseudo-NIF2 and its progeny, qGL10.1 was fine mapped to a 19.3-kb region, where a gene OsMADS56 was verified as the candidate by functional polymorphism between parental alleles. Pseudo-NIF2 strategy is a rapid way for QTL cloning, which saves 3 to 4 cropping seasons compared to the conventional way. Applying the method for cloning QTL with moderate or major effects is promising. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01408-x.

Early-Life Microbial Restitution Reduces Colitis Risk Promoted by Antibiotic-Induced Gut Dysbiosis in Interleukin 10-/- Mice.

BACKGROUND & AIMS: Perturbations in the early-life gut microbiome are associated with increased risk for complex immune disorders like inflammatory bowel diseases. We previously showed that maternal antibiotic-induced gut dysbiosis vertically transmitted to offspring increases experimental colitis risk in interleukin (IL) 10 gene deficient (IL10-/-) mice, a finding that may result from the loss/lack of essential microbes needed for appropriate immunologic education early in life. Here, we aimed to identify key microbes required for proper development of the early-life gut microbiome that decrease colitis risk in genetically susceptible animals. METHODS: Metagenomic sequencing followed by reconstruction of metagenome-assembled genomes was performed on fecal samples of IL10-/- mice with and without antibiotic-induced dysbiosis to identify potential missing microbial members needed for immunologic education. One high-value target strain was then engrafted early and/or late into the gut microbiomes of IL10-/- mice with antibiotic-induced dysbiosis. RESULTS: Early-, but not late-, life engraftment of a single dominant Bacteroides strain of non-antibiotic-treated IL10-/- mice was sufficient to restore the development of the gut microbiome, promote immune tolerance, and prevent colitis in IL10-/- mice that had antibiotic-induced dysbiosis. CONCLUSIONS: Restitution of a keystone microbial strain missing in the early-life antibiotic-induced gut dysbiosis results in recovery of the microbiome, proper development of immune tolerance, and reduced risk for colitis in genetically prone hosts.

Vinblastine-induced posterior reversible encephalopathy syndrome.

Posterior reversible encephalopathy syndrome has recently been recognized as an entity characterized by central neurological and radiological manifestations. There are increasing reports of posterior reversible encephalopathy syndrome associated with the use of chemotherapeutic agents. We herein present a case of posterior reversible encephalopathy syndrome occurring in a patient with Hodgkin's lymphoma after taking two courses of adriamycin, bleomycin, vinblastine, dacarbazine chemotherapy. A prompt recognition of posterior reversible encephalopathy syndrome associated with vinblastine and discontinuation of this drug is paramount to prevent severe neurological damage.

Immune thrombocytopenia among patients with cancer and its response to treatment.

OBJECTIVES: The aim of this study was to determine the rate of immune thrombocytopenia (ITP) in adult Jordanian patients diagnosed with cancer, to correlate this rate with the type of cancer and to assess the response of ITP in patients with cancer to treatment. METHODS: All adult patients aged 16 years or older who had been diagnosed with cancer at King Abdullah University Hospital (KAUH) between September 2002 and October 2017 were included in this study. Their medical records were reviewed for the diagnosis of ITP. RESULTS: The total number of patients diagnosed with cancer at KAUH between September 2002 and October 2017 was 8318. The majority of patients had solid cancers (87.0%), and hematological cancers constituted 13%. Fifteen (0.2%) patients with cancer had ITP. ITP was significantly more common in patients with lymphomas (1.3%) than in patients with solid cancers (0.1%) (P < .005). In the multivariate analysis and after adjusting for age and gender, patients with lymphomas were 15.2 times more likely to be diagnosed with ITP than were patients with solid cancer. CONCLUSIONS: Patients with lymphomas had higher rates of ITP than did patients with solid cancers. Treatment of ITP-associated cancer may improve the platelets count.

Adequate hemodialysis improves anemia by enhancing glucose-6-phosphate dehydrogenase activity in patients with end-stage renal disease.

BACKGROUND: We conducted this study to determine the erythrocyte glucose-6-phosphate dehydrogenase (G6PD) activity level in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) and to determine the effect of hemodialysis adequacy on G6PD activity levels and its impact on anemia. METHODS: Eighty-two patients (48 men and 34 women) receiving regular hemodialysis for ESRD through arteriovenous fistulae for at least one year prior to the start of the study were enrolled in this study. G6PD activity levels were measured in all patients and the average Kt/V was used as a parameter of HD adequacy. Patients were divided into two groups according to Kt/V values. Group 1 included 45 patients with Kt/V(˃)1.2 (adequate HD), and group 2 included 37 patients with Kt/V(˃)1.2 (inadequate HD). The average hemoglobin level and the weekly dose of an erythropoietin-stimulating agent, epoetin alpha (ESA), for each patient were calculated for one year. RESULTS: The mean (SD) erythrocyte G6PD activity for all patients on hemodialysis was 7.64 ± 1.85 U/g Hb. Patients who had received adequate hemodialysis had a significantly higher average erythrocyte G6PD (mean (SD) = 9.2 ± 0.7 U/g Hb) compared to patients who had inadequate hemodialysis (mean (SD) = 5.7 ± 0.7 U/g Hb) (P-value <0.005). The mean hemoglobin concentration was significantly higher in patients with adequate hemodialysis compared to those with inadequate hemodialysis. CONCLUSION: Our study demonstrated the beneficial effect of adequate hemodialysis in correcting anemia by enhancing the erythrocyte G6PD activity in patients.

The effect of microbiome therapy on COVID-19-induced gut dysbiosis: A narrative and systematic review.

AIMS: Emerging evidence highlights the role of COVID-19 in instigating gut dysbiosis, with repercussions on disease severity and bidirectional gut-organ communication involving the lung, heart, brain, and liver. This study aims to evaluate the efficacy of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) in addressing gut dysbiosis associated with COVID-19, as well as their impact on related disease severity and clinical outcomes. MATERIALS AND METHODS: We systematically review 27 studies exploring the efficacy of different microbiome-modulating therapies: probiotics, prebiotics, synbiotics, and fecal microbiota transplantation as potential interventions for COVID-19. KEY FINDINGS: The probiotics and synbiotics investigated encompassed a spectrum of eight bacterial and fungal genera, namely Lactobacillus, Bifidobacterium, Streptococcus, Enterococcus, Pediococcus, Bacillus, Saccharomyces, and Kluyveromyces. Noteworthy prebiotics employed in these studies included chestnut tannin, galactooligosaccharides, fructooligosaccharides, xylooligosaccharide, and resistant dextrin. The majority of the investigated biotics exhibited positive effects on COVID-19 patients, manifesting in symptom alleviation, inflammation reduction, and notable decreases in mortality rates. Five studies reported death rates, showing an average mortality ranging from 0 % to 11 % in the intervention groups, as compared to 3 % to 30 % in the control groups. Specifically, probiotics, prebiotics, and synbiotics demonstrated efficacy in diminishing the duration and severity of symptoms while significantly accelerating viral and symptomatic remission. FMT emerged as a particularly effective strategy, successfully restoring gut microbiota and ameliorating gastrointestinal disorders. SIGNIFICANCE: The insights gleaned from this review significantly contribute to our broader comprehension of the therapeutic potential of biotics in addressing COVID-19-related gut dysbiosis and mitigating secondary multi-organ complications.

Stroke as an unusual initial presentation of 'malignant' middle cerebral artery infarction involvement in systemic lupus erythematosus.

Introduction and importance: SLE, or systemic lupus erythematosus, is a chronic autoimmune condition of uncertain origin characterized by the presence of autoantibodies that target the body's own antigens. Case presentation: A 16-year-old female presented at the emergency room with a right-sided lip droop and subsequently developed symptoms consistent with a malignant hemispheric infarction, including altered consciousness, hemiplegia, and forced gaze deviation. Her laboratory results were within the normal range. However, a brain MRI revealed cerebral edema and a massive infarction in the middle cerebral artery (MCA) region. Subsequently, her serologic profile was indicative of SLE, leading to a later diagnosis. Clinical discussion: The patient in this case presented with symptoms suggestive of a stroke. A CT scan showed MCA occlusion, leading to a diagnosis of malignant MCA syndrome. The patient was also diagnosed with systemic lupus erythematosus, which is associated with an increased risk of stroke. Inflammation-induced thrombosis and CNS vasculitis are potential mechanisms linking SLE and stroke. Conclusion: This case serves as an example of a sudden and potentially life-threatening presentation of SLE, underscoring the importance of early detection and targeted treatment that can influence the course of the disease.

Multi-Institutional Study Evaluating the Role of Circulating Tumor DNA in the Management of Appendiceal Cancers.

PURPOSE: Conventional surveillance methods are poorly sensitive for monitoring appendiceal cancers (AC). This study investigated the utility of circulating tumor DNA (ctDNA) in evaluating systemic therapy response and recurrence after surgery for AC. METHODS: Patients from two specialized centers who underwent tumor-informed ctDNA testing (Signatera) were evaluated to determine the association between systemic therapy and ctDNA detection. In addition, the accuracy of ctDNA detection during surveillance for the diagnosis of recurrence after complete cytoreductive surgery (CRS) for grade 2-3 ACs with peritoneal metastases (PM) was investigated. RESULTS: In this cohort of 94 patients with AC, most had grade 2-3 tumors (84.0%) and PM (84.0%). Fifty patients completed the assay in the presence of identifiable disease, among which ctDNA was detected in 4 of 7 (57.1%), 10 of 16 (62.5%), and 19 of 27 (70.4%) patients with grade 1, 2, and 3 diseases, respectively. Patients who had recently received systemic chemotherapy had ctDNA detected less frequently (7 of 16 [43.8%] v 26 of 34 [76.5%]; odds ratio, 0.22 [95% CI, 0.06 to 0.82]; P = .02). Among 36 patients with complete CRS for grade 2-3 AC-PM, 16 (44.4%) developed recurrence (median follow-up, 19.6 months). ctDNA detection was associated with shorter recurrence-free survival (median 11.3 months v not reached; hazard ratio, 14.1 [95% CI, 1.7 to 113.8]; P = .01) and showed high accuracy for the detection of recurrence (sensitivity 93.8%, specificity 85.0%). ctDNA was more sensitive than carcinoembryonic antigen (62.5%), CA19-9 (25.0%), and CA125 (18.8%) and was the only elevated biomarker in four (25%) patients with recurrence. CONCLUSION: This study revealed a reduced ctDNA detection frequency after systemic therapy and accurate recurrence assessment after CRS. These findings underscore the role of ctDNA as a predictive and prognostic biomarker for grade 2-3 AC-PM management.

Automated, High-Throughput Platform to Generate a High-Reliability, Comprehensive Rectal Cancer Database.

PURPOSE: Dynamic operations platforms allow for cross-platform data extraction, integration, and analysis, although application of these platforms to large-scale oncology enterprises has not been described. This study presents a pipeline for automated, high-fidelity extraction, integration, and validation of cross-platform oncology data in patients undergoing treatment for rectal cancer at a single, high-volume institution. METHODS: A dynamic operations platform was used to identify patients with rectal cancer treated at MD Anderson Cancer Center between 2016 and 2022 who had magnetic resonance imaging (MRI) imaging and preoperative treatment details available in the electronic health record (EHR). Demographic, clinicopathologic, tumor mutation, radiographic, and treatment data were extracted from the EHR using a methodology adaptable to any disease site. Data accuracy was assessed by manual review. Accuracy before and after implementation of synoptic reporting was determined for MRI data. RESULTS: A total of 516 patients with localized rectal cancer were included. In the era after institutional adoption of synoptic reports, the dynamic operations platform extracted T (tumor) category data from the EHR with 95% accuracy compared with 87% before the use of synoptic reports, and N (lymph node) category with 88% compared with 58%. Correct extraction of pelvic sidewall adenopathy was 94% compared with 78%, and extramural vascular invasion accuracy was 99% compared with 89%. Neoadjuvant chemotherapy and radiation data were 99% accurate for patients who had synoptic data sources. CONCLUSION: Using dynamic operations platforms enables automated cross-platform integration of multiparameter oncology data with high fidelity in patients undergoing multimodality treatment for rectal cancer. These pipelines can be adapted to other solid tumors and, together with standardized reporting, can increase efficiency in clinical research and the translation of actionable findings toward optimizing patient outcomes.

Moyamoya disease in a 2-year-old patient from the middle east: a case report and literature review.

Introduction and importance: Moyamoya disease (MMD) is a condition characterized by progressive narrowing of arteries in the brain and abnormal development of small collateral vessels. It is commonly found in East Asia but has never been reported in Palestine. Case presentation: A 2-year-old female, part of a twin born to non-consanguineous parents, presented with recurring seizures and developmental regression. The physical examination revealed signs of hypotonia, reflex abnormalities, and bilateral Babinski signs. Comprehensive laboratory tests and imaging investigations confirmed the diagnosis of MMD, marking this patient as the reported case in Palestine. Clinical discussion: The diagnostic criteria for this condition were revised in 2021 to focus on findings seen in angiography and magnetic resonance angiography (MRA) scans. MMD has not been curative so far, and the management is focused on preventing complications, sometimes with surgical revascularization, including its different approaches: direct, indirect, and a combination of both. Conclusion: This case highlights the importance of identifying MMD in regions where it is uncommon to be diagnosed. It emphasizes the need for diagnosis and appropriate intervention to reduce complications.

Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma.

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p < 0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRASG12R had a similar OS (median 34 months), while patients with KRASQ61 and KRASG12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2-3.0, p = 0.006] and 22 months [HR: 1.7, 95% CI 1.3-2.3, p < 0.001], respectively). There was enrichment of KRASG12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2-2.4, p = 0.001) and enrichment of KRASG12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05-2.99, p = 0.04). Similar findings were observed in the external validation cohort (PanCAN's Know Your Tumor® dataset, n = 408).

Serum Tumor Markers and Outcomes in Patients With Appendiceal Adenocarcinoma.

Importance: Serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA125) have been useful in the management of gastrointestinal and gynecological cancers; however, there is limited information regarding their utility in patients with appendiceal adenocarcinoma. Objective: To assess the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes and pathologic and molecular features in patients with appendiceal adenocarcinoma. Design, Setting, and Participants: This is a retrospective cohort study at a single tertiary care comprehensive cancer center. The median (IQR) follow-up time was 52 (21-101) months. Software was used to query the MD Anderson internal patient database to identify patients with a diagnosis of appendiceal adenocarcinoma and at least 1 tumor marker measured at MD Anderson between March 2016 and May 2023. Data were analyzed from January to December 2023. Main Outcomes and Measures: Association of serum tumor markers with survival in patients with appendiceal adenocarcinoma. Cox proportional hazards regression analyses were also performed to assess associations between clinical factors (serum tumor marker levels, demographics, and patient and disease characteristics) and patient outcomes (overall survival). Results: A total of 1338 patients with appendiceal adenocarcinoma were included, with a median (range) age at diagnosis of 56.5 (22.3-89.6) years. The majority of the patients had metastatic disease (1080 patients [80.7%]). CEA was elevated in 742 of the patients tested (56%), while CA19-9 and CA125 were elevated in 381 patients (34%) and 312 patients (27%), respectively. Individually, elevation of CEA, CA19-9, or CA125 were associated with worse 5-year survival; elevated vs normal was 81% vs 95% for CEA (hazard ratio [HR], 4.0; 95% CI, 2.9-5.6), 84% vs 92% for CA19-9 (HR, 2.2; 95% CI, 1.4-3.4), and 69% vs 93% for CA125 (HR, 4.6; 95% CI, 2.7-7.8) (P < .001 for all). Quantitative evaluation of tumor markers was associated with outcomes. Patients with highly elevated (top 10th percentile) CEA, CA19-9, or CA125 had markedly worse survival, with 5-year survival rates of 59% for CEA (HR, 9.8; 95% CI, 5.3-18.0), 64% for CA19-9 (HR, 6.0; 95% CI, 3.0-11.7), and 57% for CA125 (HR, 7.6; 95% CI, 3.5-16.5) (P < .001 for all). Although metastatic tumors had higher levels of all tumor markers, when restricting survival analysis to 1080 patients with metastatic disease, elevated CEA, CA19-9, or CA125 were all still associated worse survival (HR for CEA, 3.4; 95% CI, 2.5-4.8; P < .001; HR for CA19-9, 1.8; 95% CI, 1.2-2.7; P = .002; and HR for CA125, 3.9; 95% CI, 2.4-6.4; P < .001). Interestingly, tumor grade was not associated with CEA or CA19-9 level, while CA-125 was slightly higher in high-grade tumors relative to low-grade tumors (mean value, 18.3 vs 15.0; difference, 3.3; 95% CI, 0.9-3.7; P < .001). Multivariable analysis identified an incremental increase in the risk of death with an increase in the number of elevated tumor markers, with an 11-fold increased risk of death in patients with all 3 tumor markers elevated relative to those with none elevated. Somatic mutations in KRAS and GNAS were associated with significantly higher levels of CEA and CA19-9. Conclusions and Relevance: In this retrospective study of serum tumor markers in patients with appendiceal adenocarcinoma, CEA, CA19-9, and CA125 were associated with overall survival in appendiceal adenocarcinoma. Given their value, all 3 biomarkers should be included in the initial workup of patients with a diagnosis of appendiceal adenocarcinoma.

Evaluation of protein C and S levels in patients with COVID-19 infection and their relation to disease severity.

Background: The COVID-19 pandemic has been associated with millions of deaths around the world. One of the important causes of death associated with COVID-19 was pulmonary thromboembolism. The risk for venous thromboembolism was markedly increased in patients with COVID-19 especially those admitted to the intensive care unit. The aims of our study were to measure the protein C and S levels in COVID-19-infected patients in comparison with the normal population and to assess the correlation of protein C and S levels in the plasma to the severity of infection. Methods: This was a case-control study measuring the protein C and S levels in patients infected with COVID-19 at the time of diagnosis compared to the normal population. The study included one hundred participants, sixty of them are patients with COVID-19, and forty of them are normal healthy adults. The patient group was subclassified into three subgroups according to disease severity: mild, moderate, and severe COVID-19 infections. Results: The activity of protein C in the patient group serum was significantly lower than that in the control group serum (79.35 ± 26.017 vs 97.43 ± 15.007; p < 0.001). Protein S is also significantly decreased in patients' serum when compared to the control group (70.233 ± 22.476 vs 91 ± 14.498; p < 0.001). There was a statistically significant decrease in the levels of protein C and S associated with the increase in disease severity (p < 0.05). However, protein S showed no statistically significant difference between the moderate and severe disease subgroups. Conclusion: The study concluded that the levels of protein C and S activities were both decreased in patients with COVID-19 when compared to the healthy population. It also concluded that the decrease in their levels is statistically significant in relation to the disease severity.

Statistically learning the functional landscape of microbial communities.

Microbial consortia exhibit complex functional properties in contexts ranging from soils to bioreactors to human hosts. Understanding how community composition determines function is a major goal of microbial ecology. Here we address this challenge using the concept of community-function landscapes-analogues to fitness landscapes-that capture how changes in community composition alter collective function. Using datasets that represent a broad set of community functions, from production/degradation of specific compounds to biomass generation, we show that statistically inferred landscapes quantitatively predict community functions from knowledge of species presence or absence. Crucially, community-function landscapes allow prediction without explicit knowledge of abundance dynamics or interactions between species and can be accurately trained using measurements from a small subset of all possible community compositions. The success of our approach arises from the fact that empirical community-function landscapes appear to be not rugged, meaning that they largely lack high-order epistatic contributions that would be difficult to fit with limited data. Finally, we show that this observation holds across a wide class of ecological models, suggesting community-function landscapes can be efficiently inferred across a broad range of ecological regimes. Our results open the door to the rational design of consortia without detailed knowledge of abundance dynamics or interactions.

The relative prevalence of the Omicron variant within SARS-CoV-2 infected cohorts in different countries: A systematic review.

The Omicron variant of SARS-CoV-2 was detected in October 2021 and exhibited high transmissibility, immune evasion, and reduced severity when compared to the earlier variants. The lesser vaccine effectiveness against Omicron and its reduced severity created vaccination hesitancy among the public. This review compiled data reporting the relative prevalence of Omicron as compared to the early variants to give an insight into the existing variants, which may shape the decisions regarding the targets of the newly developed vaccines. Complied data revealed more than 90% prevalence within the infected cohorts in some countries. The BA.1 subvariant predominated over the BA.2 during the early stages of the Omicron wave. Moreover, BA.4/BA.5 subvariants were detected in South Africa, USA and Italy between October 2021 and April 2022. It is therefore important to develop vaccines that protect against Omicron as well as the early variants, which are known to cause more severe complications.

Impact of KRAS Mutations and Co-mutations on Clinical Outcomes in Pancreatic Ductal Adenocarcinoma.

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 PDAC patients (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p<0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRASG12R had a similar OS (median 34 months), while patients with KRASQ61 and KRASG12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2-3.0, p=0.006] and 22 months [HR: 1.7, 95% CI 1.3-2.3, p<0.001], respectively). There was enrichment of KRASG12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2-2.4, p=0.001) and enrichment of KRASG12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05-2.99, p=0.04). Similar findings were observed in the external validation cohort (PanCAN's Know Your Tumor® dataset, n=408).

The Clinical Significance of CEA, CA19-9, and CA125 in Management of Appendiceal Adenocarcinoma.

Importance: Serum tumor markers CEA, CA19-9, & CA125 have been useful in the management of gastrointestinal and gynecological cancers, however there is limited information regarding their utility in patients with appendiceal adenocarcinoma. Objective: Assessing the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes, pathologic, and molecular features in patients with appendiceal adenocarcinoma. Design: This is a retrospective study with results reported in 2023. The median follow-up time was 43 months. Setting: Single tertiary care comprehensive cancer center. Participants: Under an approved Institutional Review Board protocol, the Palantir Foundry software system was used to query the MD Anderson internal patient database to identify patients with a diagnosis of appendiceal adenocarcinoma and at least one tumor marker measured at MD Anderson between 2016 and 2023. Results: A total of 1,338 patients with appendiceal adenocarcinoma were included, with a median age of 56.5 years. The majority of the patients had metastatic disease (80.7%). CEA was elevated in more than half of the patients tested (56%), while CA19-9 and CA125 were elevated in 34% and 27%, respectively. Individually, elevation of CEA, CA19-9, or CA125 were associated with worse 5-year survival; 82% vs 95%, 84% vs 92%, and 69% vs 93% elevated vs normal for CEA, CA19-9, and CA125 respectively (all p<0.0001). Quantitative evaluation of tumor markers increased prognostic ability. Patients with highly elevated (top 10th percentile) CEA, CA19-9 or CA125 had markedly worse survival with 5-year survival rates of 59%, 64%, and 57%, respectively (HR vs. normal : 9.8, 6.0, 7.6, all p<0.0001). Although metastatic tumors had higher levels of all tumor markers, when restricting survival analysis to 1080 patients with metastatic disease elevated CEA, CA19-9 or CA125 were all still associated worse survival (HR vs. normal : 3.4, 1.8, 3.9, p<0.0001 for CEA and CA125, p=0.0019 for CA19-9). Interestingly tumor grade was not associated with CEA or CA19-9 level, while CA-125 was slightly higher in high relative to low-grade tumors (18.3 vs. 15.0, p=0.0009). Multivariable analysis identified an incremental increase in the risk of death with an increase in the number of elevated tumor markers, with a 11-fold increased risk of death in patients with all three tumor markers elevated relative to those with none elevated. Mutation in KRAS and GNAS were associated with significantly higher levels of CEA and CA19-9. Conclusions: These findings demonstrate the utility of measuring CEA, CA19-9, and CA125 in the management of appendiceal adenocarcinoma. Given their prognostic value, all three biomarkers should be included in the initial workup of patients diagnosed with appendiceal adenocarcinoma.

Myths and Misconceptions Around Lung Cancer Causation in Palestine: Is It Time to Intervene?

PURPOSE: Having an accurate knowledge of what truly increases the likelihood of developing lung cancer (LC) may help people make better decisions about lifestyle changes that could potentially lower their risk. This study assessed current beliefs in LC causation myths among Palestinians and explored factors associated with displaying good recognition of such myths. METHODS: A national cross-sectional study was conducted from July 2019 to March 2020. A modified version of the Cancer Awareness Measure-Mythical Causes Scale was used for data collection. The awareness level of LC causation myths was determined based on the number of myths recognized to be incorrect: poor (0-4), fair (5-9), and good (10-13). RESULTS: A total of 4,817 participants completed the questionnaire of 5,174 approached (response rate = 93.1%). In total, 4,762 participants were included in the final analysis. Myths unrelated to food were more commonly recognized than food-related myths. The food-related myth most frequently recognized was eating burnt food (n = 1,427; 30.0%) followed by drinking from plastic bottles (n = 1,389; 29.2%). The food-related myth least commonly recognized was eating food containing additives (n = 737; 15.5%). The most frequently recognized myth unrelated to food was having a physical trauma (n = 2,903; 61%), whereas the least was using cleaning products (n = 1,140; 23.9%). Only 287 participants (6%) displayed good awareness. Having a chronic disease and knowing someone with cancer were associated with a decrease in the likelihood of displaying good awareness. Conversely, participants who were smoking cigarettes/shisha and those recruited from hospitals had an associated increase in the likelihood of displaying good awareness. CONCLUSION: This study found very poor awareness of LC causation myths, with only 6% recognizing ≥10 myths. Initiatives addressing LC mythical causes are needed.

Subcutaneous panniculitis-like T-cell lymphoma: an unusual cause of right thigh hypertrophy.

A man in his mid-20s presented with a painless swelling over his right thigh, which had been progressively increasing over 3 years. He underwent an excisional biopsy for the same, which showed reactive lymphadenopathy. Since the last year and a half, he developed a lower abdominal wall swelling with mild redness over it. In addition, over the last few months before presentation to haematology outpatient clinic, he experienced bouts of fever, night sweats, anorexia, weight loss and right inguinal lymphadenopathy. On examination, splenomegaly was identified. In view of the patients' symptoms, he underwent a positron emission tomography scan, which showed hypermetabolic activity in the subcutaneous tissue sparing the lymph nodes and spleen. A deep skin punch biopsy taken from his right thigh was consistent with the diagnosis of subcutaneous panniculitis-like T-cell lymphoma αß T-cell phenotype. The patient was treated successfully with oral steroids and on routine follow-up, he is in remission for 5 years.