Iron Homeostasis-Related Parameters and Hepcidin/Ferritin Ratio: Emerging Sex-Specific Predictive Markers for Metabolic Syndrome.

Metabolic syndrome (MetS) is a worldwide public health challenge. Accumulating evidence implicates elevated serum ferritin and disruptions in iron metabolism as potential elements linked to an increased risk of MetS. This study investigates the relationship between iron homeostasis-including hepcidin levels, serum iron concentration, unsaturated iron-binding capacity (UIBC), and the hepcidin/ferritin (H/F) ratio-and MetS. In this descriptive cross-sectional study, 209 participants aged 24-70 were categorized into two groups: 103 with MetS and 106 without MetS. All participants underwent medical assessment, including anthropometric measures, indices of glycemic control, lipid profiles, and iron-related parameters. Participants were further stratified by the Homeostasis Model Assessment-Insulin Resistance index into three subgroups: insulin-sensitive (IS) (<1.9), early insulin resistance (EIR) (>1.9 to <2.9), and significant insulin resistance (SIR) (>2.9). Notable increments in serum ferritin and hepcidin were observed in the SIR group relative to the IS and EIR groups, with a significant association between metabolic parameters. The UIBC and serum ferritin emerged as significant predictors of MetS, particularly in men, with an area under the curve (AUC) of 0.753 and 0.792, respectively (p ≤ 0.001). In contrast, hepcidin was notably correlated with MetS in women, with an AUC of 0.655 (p = 0.007). The H/F ratio showed superior predictive capability for MetS across both sexes (at cutoff level = 0.67). Among women, this ratio had an AUC of 0.639 (p = 0.015), and for men, it had an AUC of 0.792 (p < 0.001). Hypertension proved an independent risk factor for MetS, affirming its role in metabolic dysregulation. The findings highlight a significant interconnection between iron homeostasis parameters and MetS, with sex-specific variations underscoring the importance of personalized diagnostic criteria. The crucial role of the H/F ratio and the UIBC as emerging predictive markers for MetS indicates their potential utility in identifying at-risk individuals. Further longitudinal research is essential to establish causality and explore the interplay between these biomarkers and MetS.

A First Metabolite Analysis of Norfolk Island Pine Resin and Its Hepatoprotective Potential to Alleviate Methotrexate (MTX)-Induced Hepatic Injury.

Drug-induced liver injury (DILI) represents a significant clinical challenge characterized by hepatic dysfunction following exposure to diverse medications. Methotrexate (MTX) is a cornerstone in treating various cancers and autoimmune disorders. However, the clinical utility of MTX is overshadowed by its ability to induce hepatotoxicity. The current study aims to elucidate the hepatoprotective effect of the alcoholic extract of Egyptian Araucaria heterophylla resin (AHR) on MTX-induced liver injury in rats. AHR (100 and 200 mg/kg) significantly decreased hepatic markers (AST, ALT, and ALP), accompanied by an elevation in the antioxidant's markers (SOD, HO-1, and NQO1). AHR extract also significantly inhibited the TGF-ß/NF-κB signaling pathway as well as the downstream cascade (IL-6, JAK, STAT-3, and cyclin D). The extract significantly reduced the expression of VEGF and p38 with an elevation in the BCL2 levels, in addition to a significant decrease in the IL-1ß and TNF-α levels, with a prominent effect at a high dose (200 mg/kg). Using LC-HRMS/MS analysis, a total of 43 metabolites were tentatively identified, and diterpenes were the major class. This study presents AHR as a promising hepatoprotective agent through inhibition of the TGF-ß/NF-κB and JAK/STAT3 pathways, besides its antioxidant and anti-inflammatory effects.

Ultrasound-Guided Versus Palpation-Guided Techniques to Achieve Vascular Access in Children Undergoing Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Pediatric heart surgery is a vital therapeutic option for congenital heart disease, which is one of the most prevalent causes of death in children. Arterial cannulation (AC) and central venous catheter (CVC) are required in pediatric cardiac surgery for continuous monitoring of the central venous pressure (CVP), replacement of fluid or blood products, close hemodynamic monitoring, and frequent sampling for arterial blood gases (ABG). A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) retrieved from PubMed, Embase Cochrane, Scopus, and WOS until February 2024. Risk ratio (RR) was used to report dichotomous outcomes, and mean difference (MD) was used to report continuous outcomes, both with a 95% confidence interval (CI) using the random-effects model. Thirteen RCTs with 1060 children were included. Regarding arterial cannulation, the ultrasound-guided technique (US) was associated with a statistically significant increase in successful cannulation [RR: 1.31 with 95% CI (1.10, 1.56), P < 0.0001], and first-attempt success [RR: 1.88 with 95% CI (1.35, 2.63), P < 0.0001]. However, US was not associated with any statistically significant difference in venous cannulation in both outcomes with [RR: 1.13 with 95% CI (0.98, 1.30), P = 0.10], [RR: 1.53 with 95% CI (0.86, 2.71), P = 0.15] respectively. Moreover, US was associated with a statistically significant decrease in the number of attempts either in arterial cannulation with [MD: - 0.73 with 95% CI (- 1.00, - 0.46), P < 0.0001] or in venous cannulation with [MD: - 1.34 with 95% CI (- 2.55, - 0.12), P = 0.03], and the time of attempted cannulation also either in arterial cannulation with [MD: - 2.27 with 95% CI (- 3.38, - 1.16), P < 0.0001] or in venous cannulation with [MD: - 4.13 with 95% CI (- 7.06, - 1.19), P < 0.0001]. US guidance improves successful cannulation rates and first-attempt success in arterial access and reduces the number of attempts and procedural time for arterial and venous access. It was also associated with a lower incidence of complications and procedure failure, particularly in arterial access. However, it was associated with a higher incidence of venous puncture.

Laparoscopic versus open orchiopexy in high inguinal undescended testes, randomized clinical trial.

BACKGROUND: Traditional open orchiopexy remains the standard treatment for palpable undescended testicles (UDT). However, laparoscopic orchiopexy has recently gained attention as an alternative approach. AIM AND OBJECTIVES: This study aimed to compare the outcomes of laparoscopic versus open orchiopexy for high-inguinal undescended testes. SUBJECTS AND METHODS: A prospective randomized comparative study was conducted, involving 208 children with high inguinal undescended testes. The patients were divided into two groups: group A (104 patients) underwent laparoscopic orchiopexy and group B (104 patients) underwent open orchiopexy. RESULTS: There was a significant difference in the final testicular position between the two groups. The follow-up after 1 year showed that 100% of patients in group A had a lower testicular position, compared to 72.6% in group B. Laparoscopic orchiopexy demonstrated better outcomes in terms of achieving a lower testicular position. CONCLUSION: Both Laparoscopic and Open Orchiopexy are safe and effective for the treatment of high inguinal undescended testes. However, Laparoscopic Orchiopexy was superior to Open Orchiopexy because it was associated with better outcomes with regard to the final testicular position at the bottom of the scrotum or at a lower level below the mid-scrotal point.

The efficacy and safety of botulinum toxin epicardial fat injection to prevent postoperative atrial fibrillation in patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

Background: Postoperative atrial fibrillation (POAF) is prevalent in about 30% to 60% of patients undergoing cardiac surgery, leading to worse outcomes. Botulinum toxin type A (BTX) epicardial injection has been proposed to prevent POAF by impairing cholinergic signaling. Methods: A systematic review and meta-analysis synthesized randomized controlled trials, which were retrieved by searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through November 23, 2022. RevMan version 5.4 was used to pool dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean differences (MD) presented with the corresponding confidence interval (CI). Results: Three randomized controlled trials with 509 patients (308 in the BTX group and 205 in the placebo group) were included in the analysis. There was no difference between BTX and placebo regarding POAF incidence (RR 0.81 with 95% CI [0.65, 1.00], P = 0.05), postoperative hospital length of stay in days (MD -0.03 with 95% CI [-0.54, 0.49], P = 0.91), all-cause mortality (RR 1.64 with 95% CI [0.22, 12.17], P = 0.63), any adverse event (RR 1.03 with 95% CI [0.94, 1.12], P = 0.51), or any serious adverse event (RR 0.89 with 95% CI [0.68, 1.15], P = 0.36). Conclusion: There was no difference between the epicardial fat injection of BTX versus placebo for preventing POAF.

The efficacy and safety of pre-hospital plasma in patients at risk for hemorrhagic shock: an updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Plasma is a critical element in hemostatic resuscitation post-injury, and its prompt administration within the prehospital setting may reduce the complications resulting from hemorrhage and shock. Our objective is to assess the efficacy and safety of prehospital plasma infusion in patients susceptible to hemorrhagic shock. METHODS: We conducted our study by aggregating randomized controlled trials (RCTs) sourced from PubMed, EMBASE, Scopus, Web of Science, and Cochrane CENTRAL up to January 29, 2023. Quality assessment was implemented using the Cochrane RoB 2 tool. Our study protocol is registered in PROSPERO under ID: CRD42023397325. RESULTS: Three RCTs with 760 individuals were included. There was no difference between plasma infusion and standard care groups in 24-h mortality (P = 0.11), 30-day mortality (P = 0.12), and multiple organ failure incidences (P = 0.20). Plasma infusion was significantly better in the total 24-h volume of PRBC units (P = 0.03) and INR on arrival (P = 0.009). For all other secondary outcomes evaluated (total 24-h volume of packed FFP units, total 24-h volume of platelets units, massive transfusion, vasopressor need during the first 24 h, any adverse event, acute lung injury, transfusion reaction, and sepsis), no significant differences were observed between the two groups. CONCLUSION: Plasma infusion in trauma patients at risk of hemorrhagic shock does not significantly affect mortality or the incidence of multiple organ failure. However, it may lead to reduced packed red blood cell transfusions and increased INR at hospital arrival.

Study of aqueous humour inflammatory mediators' levels in a cohort of Egyptian patients with diabetic macular oedema.

BACKGROUND: The aim was to study aqueous humour inflammatory mediators' levels in a cohort of Egyptian patients with diabetic macular oedema (DMO). METHODS: This was a case-control prospective study conducted on 2 groups: 25 eyes of 22 (11 females) patients seeking treatment for DMO as patients group, and 10 eyes of 10 (4 females) cataract patients as a control group. Aqueous humour was aspirated before intravitreal injection (patients' group) or cataract surgery (control group). Inflammatory mediators in aqueous humour were measured using a multiplex bead immunoassay kit of 27 pre-mixed cytokines. RESULTS: Eotaxin, interferon gamma-induced protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleukin-8 (IL-8/CXCL8) were found significantly higher in patients' group compared to control group (p = 0.043, 0.037, 0.001, 0.015 respectively). On the contrary, interferon-gamma (IFN-gamma) and granulocyte colony-stimulating factor (G-CSF) were found significantly higher in control group than patients' group (p = 0.003, 0.019 respectively). Basic fibroblast growth factor (Basic-FGF/FGF-2) and interleukin-1 receptor antagonist (IL-1ra) were found higher (but not statistically significant) in controls (p = 0.100 and 0.070 respectively). Additionally, a negative and significant correlation was found between Eotaxin level in aqueous humour and central macular thickness. CONCLUSIONS: Some mediators might be implicated in the pathogenesis of DMO either augmenting or suppressing role. Eotaxin, IP-10, MCP-1 and IL-8 might have a role in cases not responding to standard anti-vascular endothelial growth factor (VEGF) therapy. IL-1ra might have a protective role; therefore, the effectiveness of intravitreal injection of IL-1ra homologue needs to be studied in future clinical trials.

Cold polypectomy techniques for small and diminutive colorectal polyps: a systematic review and network meta-analysis of randomized controlled trials.

OBJECTIVE: In the management of small and diminutive polyps, cold polypectomy is favored over electrocautery polypectomy. However, the optimal cold polypectomy technique is still controversial. Hence, this review aims to investigate the most effective cold technique for small and diminutive colorectal polyps. METHODS: We conducted a systematic review and network meta-analysis synthesizing randomized controlled trials (RCTs) which were retrieved by systematically searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through 10 February 2023. R software, (R version 4.2.0) and meta-insight software were used to pool dichotomous outcomes using risk ratio (RR) presented with the corresponding confidence interval (CI). Our protocol was prospectively published in PROSPERO with ID: CRD42022345619. RESULTS: Nineteen RCTs with 3649 patients and 4800 polyps were included in our analysis. Cold techniques (cold forceps polypectomy (CFP), jumbo forceps polypectomy (JFP), dedicated cold snare polypectomy (D-CSP), conventional cold snare polypectomy (C-CSP), underwater cold snare polypectomy (U-CSP), and cold snare endoscopic mucosal resection (CS-EMR) were included in our comparative analysis. CFP was less effective in achieving complete histological resection than C-CSP (RR: 1.10 with 95% CI [1.03-1.18]), CS-EMR (RR: 1.12 with 95% CI [1.02-1.23]), D-CSP (RR: 1.17 with 95% CI [1.04-1.32]), and U-CSP (RR: 1.21 with 95% CI [1.07-1.38]). However, the rest of the comparisons showed no difference. CONCLUSION: CFP is the least effective method for small and diminutive polyps' removal, and any snare polypectomy technique will achieve better results, warranting more large-scale RCTs to investigate the most effective snare polypectomy technique.

The impact of abdominal compression devices on colonoscopy outcomes: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Colonoscopy is the gold standard method for colorectal cancer screening. Looping occurs in 91% of cases undergoing colonoscopy and can cause patient discomfort, prolonged cecal intubation time (CIT), and colon perforation. This meta-analysis investigates the impact of abdominal compression devices (ACD) on colonoscopy outcomes. METHODS: A systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), retrieved by systematically searching: PubMed, EMBASE, WOS, SCOPUS, and Cochrane through February 2nd, 2023. Continuous and dichotomous outcomes were pooled using mean difference (MD) and risk ratio (RR) along with confidence interval (CI) using Revman. Our review protocol was prospectively published on PROSPERO with ID: CRD42023397344. RESULTS: We included eight RCTs with a total of 1,889 patients. ACD was effective to decrease CIT (MD: -2.15 with a 95% CI [-3.49, -0.80], p = .002), postural change (RR: 0.57 with 95% CI [0.49, 0.66], p = .00001), and VAS pain score (MD: -1.49 with 95% CI [-1.81, -1.17], p = .0001). However, there was no difference between ACD and control groups regarding manual compression (RR: 0.65 with 95% CI [0.42, 1.00], p = .05), complete colonoscopy rate (CCR) (RR: 1.01 with 95% CI [0.99, 1.04], p = .31), and cecal intubation length (CIL) (MD: -2.25 with 95% CI [-7.64, 3.14], p = .41). CONCLUSION: ACD during colonoscopy may enhance patient comfort by reducing CIT, pain, and postural changes. Nevertheless, additional RCTs are necessary to validate these results and determine the most suitable approach to utilize ACD for colonoscopy.

The efficacy and safety of olokizumab for rheumatoid arthritis: a systematic review, pairwise, and network meta-analysis.

Olokizumab (OKZ) is a novel IL-6 inhibitor that directly targets IL-6 rather than its receptor. We aim to evaluate the efficacy and safety of OKZ for patients with rheumatoid arthritis (RA) and to investigate the optimal treatment regimen. A systematic review, pairwise, and network meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, CENTRAL, SCOPUS, EMBASE, and PubMed until August 31, 2022. We used the risk ratio (RR) and mean difference (MD) for dichotomous and continuous outcomes, respectively, presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022358082. Five RCTs with 2277 patients were included. OKZ significantly improved the American College of Rheumatology criteria (ACR) 20 (RR: 1.97 with 95% CI [1.49, 2.58], P = 0.00001), ACR50 (RR: 3.83 with 95% CI [2.13, 6.87], P = 0.00001), ACR70 (RR: 3.83 with 95% CI [2.13, 6.87], P = 0.00001), disease activity score 28 based on C-reactive protein (DAS28-CRP) (RR: 3.91 with 95% CI [2.65, 5.79], P = 0.00001), clinical disease activity index (CDAI) (RR: 2.80 with 95% CI [1.43, 5.48], P = 0.003), and health assessment questionnaire disability index (HAQ-DI) (MD: - 0.28 with 95% CI [- 0.38, - 0.18], P = 0.00001) after 12 weeks, compared to placebo. However, OKZ was also associated with a higher incidence of any adverse events (AEs) (RR: 1.15 with 95% CI [1.06, 1.25], P = 0.0005) and AEs leading to drug discontinuation (RR: 1.86 with 95% CI [1.05, 3.29], P = 0.03). OKZ is effective and with acceptable safety profile when administrated with methotrexate in patients with RA not adequately controlled by tumor necrosis factor inhibitors; however, more large-scale RCTs are still required to investigate the optimal dosing, long-term effects, and comparative efficacy versus established biological DMARDs. Key Points • OKZ is effective especially with methotrexate in RA patients.

Cold Versus Hot Snare Polypectomy for Colorectal Polyps: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: Endoscopic polypectomy is an excellent tool for colon cancer prevention. With the innovation of novel resection techniques, the best method is still being investigated. Hence, we aim to evaluate the efficacy and safety of cold snare polypectomy (CSP) versus hot snare polypectomy (HSP) for colorectal polyp resection. METHODS: A systematic review and meta-analysis synthesizing evidence from randomized controlled trials retrieved from PubMed, EMBASE, WOS, SCOPUS, and CENTRAL until July 16, 2022. We pooled dichotomous outcomes using risk ratio (RR) with the corresponding CI. This review's protocol was prospectively registered in PROSPERO with ID: CRD42022347496. RESULTS: We included 18 randomized controlled trials with a total of 4317 patients and 7509 polyps. Pooled RR favored HSP regarding the complete resection rate (RR: 0.96 with 95% CI: 0.95, 1, P = 0.03) and local recurrence incidence (RR: 5.74 with 95% CI: 1.27, 25.8, P = 0.02). Pooled RR favored CSP regarding the colonoscopy time (mean difference: -6.50 with 95% CI: -7.55, -5.44, P = 0.00001) and polypectomy time (mean difference: -57.36 with 95% CI: -81.74, -32.98, P = 0.00001). There was no difference regarding the incidence of immediate bleeding ( P = 0.06) and perforation ( P = 0.39); however, HSP was associated with more incidence of delayed bleeding ( P = 0.01), abdominal pain ( P = 0.007), and postresection syndrome ( P = 0.02). DISCUSSION: HSP is associated with a higher complete resection and lower recurrence rates; however, HSP is also associated with a higher incidence of adverse events. Therefore, improving the complete resection rate with CSP still warrants more innovation, giving the technique safety and shorter procedure duration.

Olokizumab's Effectiveness and Safety in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: In the development of rheumatoid arthritis, the cytokine interleukin-6 plays a role. An interleukin-6 cytokine-specific monoclonal antibody called olokizumab directly targets this cytokine. OKZ effectiveness and safety are being evaluated through this meta-analysis. METHOD: I looked up every published randomized controlled study on Clinicaltrials.gov, Scopus, Web of Science, Cochrane, and PubMed. I conducted the study using both the Mantel-Haenszel and inverse variance approaches. I evaluated bias in the included studies using the risk of bias tool 2. RESULTS: In this meta-analysis, five trials totalling 2227 participants, were examined. In contrast to the placebo group, the olokizumab group had a significantly higher incidence of American College of Rheumatology 20; RR = 1.83, 95% CI [1.69, 1.99], P < 0.00001. Regarding Health Assessment Questionnaire-Disability Index improvement, olokizumab significantly outperformed the placebo group; MD = -0.28, 95% CI [-0.32, -0.24], P < 0.00001. The incidence of treatment-emergent adverse events was significantly higher in the olokizumab group than in the placebo group; RR = 1.10, 95% CI [1.04, 1.17], P = 0.0006. Furthermore, the incidence of treatment-emergent serious adverse events did not differ significantly between the olokizumab group and the placebo group; RR = 0.85, 95% CI [0.60, 1.20], P = 0.35. CONCLUSION: In patients with rheumatoid arthritis, olokizumab combined methotrexate is well tolerated and more effective than placebo plus methotrexate.

Early perioperative versus postoperative meloxicam for pain control in patients undergoing orthopedic surgery: a systematic review and Meta-analysis of randomized controlled trials.

OBJECTIVE: Post-orthopaedic operative pain is a serious concern that often requires the administration of analgesics; however, the optimal time of analgesic administration is still inconclusive. Perioperative analgesia is administrating pre-emptive analgesia before and during the surgery followed by postoperative analgesia to decrease the procedure associated nociceptive response. We aim to assess perioperative meloxicam versus postoperative meloxicam for pain control after orthopaedic operations. METHODS: A systematic review and meta-analysis involving randomized controlled trials from PubMed, Embase, Scopus, WOS, and Cochrane until 28th May 2022. We pooled dichotomous outcomes using risk ratio (RR) presented with a 95% confidence interval (CI) and continuous outcomes using mean difference (MD) with 95% CI. We registered our protocol in PROSPERO with ID: CRD42022336046. RESULTS: We included five RCTs with 964 patients. All the included trials showed high risk of performance and detection biases because of lack of blinding. Pooled analysis favored perioperative meloxicam in reducing pain score after six hours (MD: -0.42 with 95% CI [-0.63, -0.21], p = .0001), 12 h (MD: -0.54 with 95% CI [-0.69, -0.39], p = .00001), and 24 h (MD: -0.23 with 95% CI [-0.36, -0.10]. Pooled analysis favored perioperative meloxicam in improving patient global assessment scale after 12 h (MD: -0.66 with 95% CI [-0.86, -0.46], p = .00001), 24 h (MD: -0.30 with 95% CI [-0.49, -0.11, p = .002), and 48 h (MD: -0.17 with 95% CI [-0.33, -0.01], p = .04). Pooled analysis favored perioperative meloxicam in reducing patient-controlled analgesia (MD: -4.25 with 95% CI [-5.96, -2.54], p = .00001). CONCLUSION: Short-term pain management after orthopaedic procedures is better accomplished with perioperative meloxicam than postoperative meloxicam. Before recommending perioperative meloxicam for pain control following orthopaedic surgeries, further multicentre trials are still warranted to examine the impact of perioperative meloxicam in different orthopaedic procedures.

Selective elimination of immunosuppressive T cells in patients with multiple myeloma.

Elimination of suppressive T cells may enable and enhance cancer immunotherapy. Here, we demonstrate that the cell membrane protein SLAMF7 was highly expressed on immunosuppressive CD8+CD28-CD57+ Tregs in multiple myeloma (MM). SLAMF7 expression associated with T cell exhaustion surface markers and exhaustion-related transcription factor signatures. T cells from patients with a high frequency of SLAMF7+CD8+ T cells exhibited decreased immunoreactivity towards the MART-1aa26-35*A27L antigen. A monoclonal anti-SLAMF7 antibody (elotuzumab) specifically depleted SLAMF7+CD8+ T cells in vitro and in vivo via macrophage-mediated antibody-dependent cellular phagocytosis (ADCP). Anti-SLAMF7 treatment of MM patients depleted suppressive T cells in peripheral blood. These data highlight SLAMF7 as a marker for suppressive CD8+ Treg and suggest that anti-SLAMF7 antibodies can be used to boost anti-tumoral immune responses in cancer patients.

AKT-dependent NOTCH3 activation drives tumor progression in a model of mesenchymal colorectal cancer.

Recently, a transcriptome-based consensus molecular subtype (CMS) classification of colorectal cancer (CRC) has been established, which may ultimately help to individualize CRC therapy. However, the lack of animal models that faithfully recapitulate the different molecular subtypes impedes adequate preclinical testing of stratified therapeutic concepts. Here, we demonstrate that constitutive AKT activation in intestinal epithelial cells markedly enhances tumor invasion and metastasis in Trp53ΔIEC mice (Trp53ΔIECAktE17K) upon challenge with the carcinogen azoxymethane. Gene-expression profiling indicates that Trp53ΔIECAktE17K tumors resemble the human mesenchymal colorectal cancer subtype (CMS4), which is characterized by the poorest survival rate among the four CMSs. Trp53ΔIECAktE17K tumor cells are characterized by Notch3 up-regulation, and treatment of Trp53ΔIECAktE17K mice with a NOTCH3-inhibiting antibody reduces invasion and metastasis. In CRC patients, NOTCH3 expression correlates positively with tumor grading and the presence of lymph node as well as distant metastases and is specifically up-regulated in CMS4 tumors. Therefore, we suggest NOTCH3 as a putative target for advanced CMS4 CRC patients.

Evaluation of mediastinal lymphadenopathy by diffusion weighted MRI; correlation with histopathological results.

INTRODUCTION: Diffusion weighted imaging (DWI) has shown its potential as a reliable noninvasive technique for tissue characterization. DWI reflects the tissue specific diffusion capacity which can be used for tissue characterization. Hypercellular tissue (e.g; malignant tumors) had restricted diffusion capacity with increased signals on DWI and low ADC values. Non-tumoral tissues show low cellularity, and diffusion capacity is not restricted resulting in signal loss on DWI and high apparent diffusion coefficient (ADC). Differential diagnosis of mediastinal lymphadenopathy is an issue of debate, especially in malignant benign differentiation. Diffusion weighted imaging with magnetic resonance could improve the diagnostic accuracy in differentiation between benign and malignant mediastinal nodes. OBJECTIVES: to determine the efficacy of diffusion weighted MRI in evaluation of mediastinal lymphadenopathy with histopathological correlation to differentiate benign from malignant lymph nodes. MATERIAL AND METHODS: 30 patients with mediastinal lymphadenopathy underwent diffusion weighted MRI. ADCs of lymph nodes were derived and constructed from b = 0 and b = 1000 sec/mm2 values by drawing regions of interests (ROI). Consequently, mediastinal nodes were studied, biopsies and histopathological analysis were done after MRI examination. RESULTS: The best cutoff point of ADC to differentiate benign from malignant lesions was 1.15 mm/sec (sensitivity 77%, specificity 92% and AUC 81.4%). Significant negative correlation of ADC by DW MRI and the size of the LNs. The mean ADC values in the lymphoma group was lower than in the sarcoidosis group, and the difference was statistically significant. CONCLUSION: The study supports that MRI with diffusion weighted images can differentiate benign from malignant mediastinal lymphadenopathy and differentiate lymphoma from sarcoidosis non-invasively.