Downregulation of plasma MiR-142-3p and MiR-26a-5p in patients with colorectal carcinoma

Background: Colorectal cancer is one of the most commonly diagnosed cancers and cancer- related death worldwide. Identification of new specific biomarkers could be helpful to detection of this malignancy. Altered plasma microRNA expression has been identified in many cancers, including colorectal cancer. Objectives: The main objective of this study was to identify the circulating microRNAs with the most expression changes in colorectal cancer patients compared with neoplasm free healthy individuals. Materials and Methods: MicroRNA expression profiling was performed on plasma samples of 37 colorectal cancer patients and 8 normal subjects using microRNA microarray. Quantitative real-time reverse transcription polymerase chain reaction was used to validate the two selected altered microR NAs. Plasma samples from 61 colorectal cancer patients and 24 normal subjects were used in our validation study. Results: In profiling study we found a panel of six plasma microRNAs with significant downregulation. MicroRNA-142-3p and microRNA-26a-5p were selected and validated by polymerase chain reaction. Our results demonstrated that expression levels of plasma microRNA-142-3p and microRNA-26a-5p were significantly downregulated in patients with colorectal cancer when compared to control group. Conclusions: Our findings suggest that downregulation of plasma microRNA-142-3p and microRNA-26a-5p might serve as novel noninvasive biomarkers in the diagnosis of colorectal cancer, although more studies are needed to highlight the theoretical strengths. © 2015, Iranian Journal of Cancer Prevention

Management of Postoperative Peritonitis in Low-resources Services

Background. Postoperative peritonitis (PP) reminds one of the most difficult complications in abdominal surgery with mortality rate 22.3 – 90 %.Methods. In Ivano-Frankivsk Regional (tertiary level) Clinical Hospital (Ivano-Frankivsk, Ukraine) during 2010–2017 were operated 8762 patients with acute and chronic diseases of digestive system (appendicitis, pancreatitis, cholecystitis, bowel obstruction, complicated ulcer of upper gastrointestinal truck, mesenteric vessels thrombosis, abdominal adhesion diseases, hernia, Chron\u27s diseases, abdominal trauma), among them in 209 (2.4 %) patients developed PP. Local PP (abscess of abdominal cavity) had 142 (67.9 %), diffuse PP – 67 (42.1 %) patients.Results. Clear local symptoms of peritonitis were absent in 178 (85.1 %) of 209 patients. General complication, such as acute respiratory failure had 95 (45.5 %), cardiovascular insufficiency – 68 (32.5 %), hepato-renal dysfunction - 46 (22 %) patients with PP. 129 (61.7 %) patients were treated by minimally invasive approach: 24 patients had laparoscopic lavage with drain of abdominal cavity abscess and 105 - ultrasound guided drain of abscess with catheter. 80 (38.3 %) patients had re-laparotomy (RL): 61 (91 %) from 67 with diffuse PP, 19 (13.4 %) from 142 patients – with local PP. 46 (57.5 %) patients underwent one RL, 26 (32.5 %) – two, 8 (10 %) patients – three RL. With increasing numbers of RL, increase mortality rate: after first RL died 7 (15.2 %) of 46 patients, after second RL – 12 (63.2 %) of 19, after third RL 6 (75 %) of 8 patients.Conclusions. Together with standard surgical methods and precise technique were used lavage of abdominal cavity with 8 – 12 litres of antiseptic solutions, solution for peritoneal dialysis intraabdominally, nasointestinal drain tube, what was favourable for faster treatment of abdominal sepsis, reducing number of RL and postoperative mortality

MiR-142-3p is downregulated in aggressive p53 mutant mouse models of pancreatic ductal adenocarcinoma by hypermethylation of its locus

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease with poor prognostic implications. This is partly due to a large proportion of PDACs carrying mutations in TP53, which impart gain-of-function characteristics that promote metastasis. There is evidence that microRNAs (miRNAs) may play a role in both gain-of-function TP53 mutations and metastasis, but this has not been fully explored in PDAC. Here we set out to identify miRNAs which are specifically dysregulated in metastatic PDAC. To achieve this, we utilised established mouse models of PDAC to profile miRNA expression in primary tumours expressing the metastasis-inducing mutant p53R172H and compared these to two control models carrying mutations, which promote tumour progression but do not induce metastasis. We show that a subset of miRNAs are dysregulated in mouse PDAC tumour tissues expressing mutant p53R172H, primary cell lines derived from mice with the same mutations and in TP53 null cells with ectopic expression of the orthologous human mutation, p53R175H. Specifically, miR-142-3p is downregulated in all of these experimental models. We found that DNA methyltransferase 1 (Dnmt1) is upregulated in tumour tissue and cell lines, which express p53R172H. Inhibition or depletion of Dnmt1 restores miR-142-3p expression. Overexpression of miR-142-3p attenuates the invasive capacity of p53R172H-expressing tumour cells. MiR-142-3p dysregulation is known to be associated with cancer progression, metastasis and the miRNA is downregulated in patients with PDAC. Here we link TP53 gain-of-function mutations to Dnmt1 expression and in turn miR-142-3p expression. Additionally, we show a correlation between expression of these genes and patient survival, suggesting that they may have potential to be therapeutic targets

Association of Circulating MicroRNA-142-3p with Graves Disease

تهدف هذه الدراسة الى التحري عن وجود دور محتمل للحامض النووي الرايبي الدقيق(miR-142-3p) في ظهور مرض اعتلال الغدةالدرقية المفرط (Graves disease ) وعلاقته مع افراز الاجسام المضادة لمستقبلات الهرمون المحفز للدرقية ( TSHR-Ab )تضمنتالدراسة اخذ عينات دم من اربعين مريضا يعانون من مرض اعتلال الغدة الدرقية المفرط وكانت نتيجة فحص وجود الاجسام المضادة لديهم(TSHR-Ab) موجبة. تم تقسيم المرضى الى مجموعتين (22 مريضا دون علاج و 18 مريضا يأخذ علاج) بالاضافة الى اربعين شخصا منالاصحاء كمجموعة ضابطة. جميع المرضى والاصحاء لايعانون من اي من امراض المناعة الذاتية. تم قياس مستوى تعبير (miR-142-3p)باستخدام تقنية (RT-PCR ). اظهرت النتائج ان هناك زيادة معنوية (p < 0.01 ) في تعبير) miR-142-3p) في مصل دم كل منمجموعتي المرضى مقارنة بالمجموعة الضابطة وفي المرضى الذين يكون لديهم وراثة بالعائلة مقارنة بالذين لم يكن لديهم. بينما كان الفرق فيمستوى تعبير ) miR-142-3p) غير معنوي ( p >0.05 ) بين مجموعتي المرضى. كما اظهرت النتائج ان هناك علاقة موجبة بين مستوىتعبير ) miR-142-3p) مع تركيز الاجسام المضادة (TSHR-Ab ) FT3 ,وFT4, بالاضافة الى ان هذا الحامض النووي الرايبي له قيمةتشخيصية دقيقة ذات حساسية (83%) وخصوصية (80%).نستنتج من هذه الدراسة ان الاختلاف في مستوى تعبير ) miR-142-3p) بينمرضى اعتلال الغدة الدرقية المفرط والاصحاء جعلته ذا قيمة تشخيصية جيدة و من علاقته الموجبة مع تركيز الاجسام المضادة ((TSHR-Ab نستنتجThis study aims to investigate the possible role of circulating microRNA-142-3p (miR-142-3p) in thedevelopment of graves disease (GD) and its association with the antibody directed against thyroidstimulating hormone receptor (TSHR-Ab) production in patients with GD. Forty patients with positiveTSHR-Ab enrolled in this study were divided ,based on treatment, into (22 untreated (newly diagnosed) and18 treated patients) and based on family history (30 with positive family history and 10 with negative familyhistory). In addition to forty healthy subjects with sex and age matching as a control group. The expressionlevel of circulating miR-142-3p was determined by two steps reverse transcription polymerase chain reaction(RT-PCR) technique. Results show that there is a significant elevation (p < 0.01) in the expression of miR-142-3p in the serum of both treated and untreated patients compared with controls and in patients withpositive family history compared with negative family history. While its expression is non-significantlylower (P > 0.05) in the serum of treated patients compared with untreated ones. It has been found that miR-142-3p expression was positively correlated with levels of TSHR-Ab, FT3, and FT4. In addition, the miR-142-3p expression has a good diagnostic accuracy with sensitivity (82%) and specificity (80%). Inconclusion, the differential expression of miR-142-3p between patients and healthy controls appears as apotential biomarker for diagnosis of GD and the positive correlation of miR-142-3p with TSHR-Absuggesting the contribution of this miRNA in the development of GD

The use of FDG-PET in the initial staging of 142 patients with follicular lymphoma: a retrospective study from the FOLL05 randomized trial of the Fondazione Italiana Linfomi

BACKGROUND: The role of [(18)F] fluorodeoxyglucose (FDG)-positron emission tomography (PET) in follicular lymphoma (FL) staging is not yet determined. PATIENTS AND METHODS: The aim of the present study was to investigate the role of PET in the initial staging of FL patients enrolled in the FOLL05-phase-III trial that compared first-line regimens (R-CVP, R-CHOP and R-FM). Patients should have undergone conventional staging and have available PET baseline to be included. RESULTS: A total of 142 patients were analysed. PET identified a higher number of nodal areas in 32% (46 of 142) of patients and more extranodal (EN) sites than computed tomography (CT) scan. Also, the Follicular Lymphoma International Prognostic Index (FLIPI) score increased in 18% (26 of 142) and decreased in 6% (9 of 142) of patients. Overall, the impact of PET on modifying the stage was highest in patients with limited stage. Actually, 62% (15 of 24) of cases with limited disease were upstaged with PET. CONCLUSIONS: The inclusion of PET among staging procedures makes the evaluation of patients with FL more accurate and has the potential to modify therapy decision and prognosis in a moderate proportion of patients. Further prospective clinical trials on FL should incorporate PET at different moments, and the therapeutic criteria to start therapy should be re-visited in the views of this new tool

Long-term survival after aortic valve replacement with the Mitroflow bioprosthesis : a comparative study

Background Recent case reports of early structural degeneration of the Mitroflow valve have cast doubts on the suitability of this bioprosthesis, particularly in the smaller sizes, and in younger patients. We studied long-term patient survival, in a comparative study, as a marker of success after aortic valve replacement. Methods Long-term survival in 142 consecutive patients implanted with the Mitroflow valve was compared, using the Kaplan-Meier method, with a control group of 149 patients receiving different bioprostheses. Ninety two percent of patients were over 70 years and the Mitroflow was used preferentially in smaller sizes. Results Long-term survival in patients who received a Mitroflow valve was equivalent to controls. Four documented cases of premature structural valve degeneration (3 Mitroflow, 1 Perimount) required a second intervention. Conclusions The Mitroflow compared favorably with other valves in our practice. Although a few patients required further treatment this had no significant adverse impact on overall survival.peer-reviewe

Effectiveness of ustekinumab dose escalation in Crohn's disease patients with insufficient response to standard-dose subcutaneous maintenance therapy

Background Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose-optimisation for ustekinumab nonresponse is limited.Aim To assess the effectiveness of dose escalation of ustekinumab.Methods This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard-dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation.Results A total of 142 patients (22 centres/14 countries) were included. The patients were dose-escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid-free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow-up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow-up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission.Conclusions Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing

Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications.

BCR/ABL1-like acute lymphoblastic leukaemia (ALL) is a subgroup of B-lineage acute lymphoblastic leukaemia that occurs within cases without recurrent molecular rearrangements. Gene expression profiling (GEP) can identify these cases but it is expensive and not widely available. Using GEP, we identified 10 genes specifically overexpressed by BCR/ABL1-like ALL cases and used their expression values - assessed by quantitative real time-polymerase chain reaction (Q-RT-PCR) in 26 BCR/ABL1-like and 26 non-BCR/ABL1-like cases to build a statistical "BCR/ABL1-like predictor", for the identification of BCR/ABL1-like cases. By screening 142 B-lineage ALL patients with the "BCR/ABL1-like predictor", we identified 28/142 BCR/ABL1-like patients (19·7%). Overall, BCR/ABL1-like cases were enriched in JAK/STAT mutations (P < 0·001), IKZF1 deletions (P < 0·001) and rearrangements involving cytokine receptors and tyrosine kinases (P = 0·001), thus corroborating the validity of the prediction. Clinically, the BCR/ABL1-like cases identified by the BCR/ABL1-like predictor achieved a lower rate of complete remission (P = 0·014) and a worse event-free survival (P = 0·0009) compared to non-BCR/ABL1-like ALL. Consistently, primary cells from BCR/ABL1-like cases responded in vitro to ponatinib. We propose a simple tool based on Q-RT-PCR and a statistical model that is capable of easily, quickly and reliably identifying BCR/ABL1-like ALL cases at diagnosis

Custom Made Candy Plug for Distal False Lumen Occlusion in Aortic Dissection: International Experience

Objective: To evaluate early and midterm outcomes of the Candy Plug (CP) technique for distal false lumen (FL) occlusion in thoracic endovascular aortic repair for aortic dissection (AD) in a more real world cohort of patients from an international multicentre registry. Methods: A multicentre retrospective study was conducted of all consecutive patients from the contributing centres with subacute and chronic AD treated with the CP technique from October 2013 to April 2020 at 18 centres. Results: A custom made CP was used in 155 patients (92 males, mean age 62 ± 11 years). Fourteen (9%) presented with ruptured false lumen aneurysms. Technical success was achieved in all patients (100%). Clinical success was achieved in 138 patients (89%). The median hospital stay was 7 days (1 – 77). The 30 day mortality rate was 3% (n = 5). Stroke occurred in four patients (3%). Spinal cord ischaemia occurred in three patients (2%). The 30 day computed tomography angiogram (CTA) confirmed successful CP placement at the intended level in all patients. Early complete FL occlusion was achieved in 120 patients (77%). Early (30 day) CP related re-intervention was required in four patients (3%). The early (30 day) stent graft related re-intervention rate was 8% (n = 12). Follow up CTA was available in 142 patients (92%), with a median follow up of 23 months (6 – 87). Aneurysmal regression was achieved in 68 of 142 patients (47%); the aneurysm diameter remained stable in 69 of 142 patients (49%) and increased in five of 142 patients (4%). A higher rate of early FL occlusion was detected in the largest volume centre patients (50 [88%] vs. 70 [71%] from other centres; p = .019). No other differences in outcome were identified regarding volume of cases or learning curve. Conclusion: This international CP technique experience confirmed its feasibility and low mortality and morbidity rates. Aortic remodelling and false lumen thrombosis rates were high and support the concept of distal FL occlusion in AD using the CP technique