Halochromic smart packaging film based on montmorillonite/polyvinyl alcohol-high amylose starch nanocomposite for monitoring chicken meat freshness.

Polyvinyl alcohol (PVA) was blended with high amylose starch (HAS) at a ratio of 3:1, and reinforced with montmorillonite (MMT K10) at different concentrations (1, 2, 5, and 7 % w/w of polymers) and anthocyanins (ANT) to develop an active and smart packaging film. MMT addition enhanced the film's mechanical, barrier, thermal, and water resistance properties. Incorporating ANT extracted from roselle calyx into the optimal nanocomposite film (MMT/PVA-HAS II) increased the films' antioxidant, pH-response, and antibacterial properties. FTIR, XRD, and SEM confirmed the intermolecular interactions and even distribution of ANT and MMT in the film matrix. Release rate of ANT was dependent on type of simulant, with higher rate in aqueous solutions compared to alcoholic/fatty food simulants, and cytotoxicity evaluation proved safety of films for food packaging applications. Storage experiments confirmed the potential applicability of the novel halochromic smart film as a promising candidate for monitoring chicken spoilage under abusive storage conditions.

Serum miRNA-21, miRNA-146a and plasma cell free DNA as novel biomarkers for assessing systemic lupus erythematosus activity.

BACKGROUND: MicroRNA and cell-free DNA have shown significant correlations with several autoimmune disorders including systemic lupus erythematosus (SLE). SLE has been associated with challenges in determining its activity, so that the need for biomarkers contributing to assessing its activity is emerging. The current study investigated miRNA-21, miRNA-146a and plasma cf-DNA in determination of SLE activity, in addition their association with clinical data including complement factor 3 (C3), complement factor(C4), anti-dsDNA, and other disease activity indices. METHODS AND RESULTS: Eighty subjects divided into; twenty active patients (with SLE-DAI2K score of 16-18) twenty inactive patients (with SLE-DAI2K score of 1-3), and forty healthy control participants) were included in this study. Serum miR-21, miR-146a, and plasma cf-DNA were quantified by real time PCR and their correlation with clinical data was statistically analyzed. The results demonstrated that active cases have significant upregulation of serum miRNA-21 and plasma cf-DNA. Moreover, miR-21 showed a negative, significant pertaining to C3, C4 and was positively related to Systemic Lupus Erythematosus Disease Activity Index 2 K score (SLE-DAI Index2K score) and Systemic-Lupus-Erythematosus-Disease Activity-Index 2 K activity (SLE-DAI 2 K activity). Also, Active group miRNA-146a was negatively, significantly correlated with C3, as well as a positive significant relationship with SLE-DAI2K score and SLEDAI 2 K activity, in addition to anti DNA Autoantibodies. Furthermore, miR-21 and cf-DNA demonstrated a differential value through Receiver Operating Characteristic (ROC) curve's study. CONCLUSIONS: the present study illustrated miR-21, miR-146a, and cf-DNA relationship with SLE clinical data. In addition to their potential value in SLE diagnosis, and activity determination.

Microbiota and parasite relationship.

The diversity of microbiota is different in each person. Many health problems such as autoimmune diseases, diabetes, cardiovascular diseases, and depression can be caused by microbiota imbalance. Since the parasite needs a host to survive, it interacts closely with the microbiota elements. Blastocystis acts on the inflammatory state of the intestine and may cause various gastrointestinal symptoms, on the contrary, it is more important for gut health because it causes bacterial diversity and richness. Blastocystis is associated with changes in gut microbiota composition, the ultimate indicator of which is the Firmicutes/Bacteroidetes ratio. The Bifidobacterium genus was significantly reduced in IBS patients and Blastocystis, and there is a significant decrease in Faecalibacterium prausnitzii, which has anti-inflammatory properties in Blastocystis infection without IBS. Lactobacillus species reduce the presence of Giardia, and the produced bacteriocins prevent parasite adhesion. The presence of helminths has been strongly associated with the transition from Bacteroidetes to Firmicutes and Clostridia. Contrary to Ascaris, alpha diversity in the intestinal microbiota decreases in chronic Trichuris muris infection, and growth and nutrient metabolism efficiency can be suppressed. Helminth infections indirectly affect mood and behavior in children through their effects on microbiota change. The main and focus of this review is to address the relationship of parasites with microbiota elements and to review the data about what changes they cause. Microbiota studies have gained importance recently and it is thought that it will contribute to the treatment of many diseases as well as in the fight against parasitic diseases in the future.

Genome-Wide Discovery of Structural Variants Reveals Distinct Variant Dynamics for Two Closely Related Monilinia Species.

Structural variants (SVs) are variants with sizes bigger than 50 bp and capable of changing the size, copy number, location, orientation, and sequence content of genomic DNA. Although these variants have been proven to be extensive and involved in many evolutionary processes along the tree of life, there is still insufficient information on many fungal plant pathogens. In this study, the extent of SVs, as well as single-nucleotide polymorphisms (SNPs), has been determined for two prominent species of the Monilinia genus (the causal agents of brown rot disease in pome and stone fruits): Monilinia fructicola and Monilinia laxa for the first time. The genomes of M. fructicola were found to be more variant-rich in contrast to M. laxa based on the reference-based variant calling (with a total number of 266.618 and 190.599 SNPs and 1,540 and 918 SVs, respectively). The extent, as well as distribution of SVs, presented high conservation within the species and high diversity between the species. Investigation of potential functional effects of characterized variants revealed high potential relevance of SVs. Moreover, the detailed characterization of copy number variations (CNVs) for each isolate revealed that around 0.67% of M. fructicola genomes and 2.06% of M. laxa genomes are copy number variables. The variant catalog as well as distinct variant dynamics within and between the species presented in this study opens doors for many further research questions.

Novel pectin-based nanocomposite film for active food packaging applications.

Novel pectin-based films reinforced with crystalline nanocellulose (CNC) and activated with zinc oxide nanoparticles (ZnO NPs) were prepared by solvent-casting method. Film ingredients enhanced UV-blocking, thermal, and antibacterial properties of active films against well-known foodborne pathogens. Optimal active films exhibited higher mechanical, water vapor barrier properties compared to pristine pectin films. SEM confirmed the even distribution of CNC and ZnO NPs in pectin matrix and their interactions were proven using FTIR. Wrapping hard cheese samples artificially contaminated with Staphylococcus aureus and Salmonella enterica with the ternary nanocomposite film at 7 °C for 5 days significantly reduced the total population counts by at least 1.02 log CFU/g. Zn2+ migrating to wrapped cheese samples was below the specific limit (5 mg/kg), confirming their safety for food contact. Overall, ZnO/CNC/pectin nanocomposite films represent promising candidates for active food packaging as safe, eco-friendly alternatives for synthetic packaging materials.

Russell Body Esophagitis: A Possible Indication to Screen for Hematologic Malignancy.

This is a case of an elderly man with lymphoplasmacytic lymphoma on a direct oral anticoagulant for atrial fibrillation who presented with weakness. Esophagogastroduodenoscopy found herpes esophagitis and islands of salmon-colored mucosa suspicious for Barrett's esophagus. Biopsies showed no signs of Barrett's Esophagus but returned positive for Russell bodies. This is the only reported case of Russell body esophagitis in the absence of Barrett's esophagus. This case adds to the mounting evidence that Russell body esophagitis and potentially all gastrointestinal Russell bodies should prompt further work-up for hematologic malignancy.

Latest Insights on the Diagnostic Approaches and Treatment Strategies of COVID-19.

BACKGROUND: COVID-19 has emerged as the most serious pandemic in the 21st century to date. COVID-19 patients may develop various disease symptoms that hinder the accurate clinical diagnosis. SUMMARY: Routine diagnosis of COVID-19 requires complementary investigations, including computed tomography, immunological assays, and molecular assays like real-time RT-PCR, loop-mediated isothermal amplification, metagenomic next-generation sequencing, and clusters of regularly interspaced short palindromic repeats-based assays. Clinically approved antiviral drugs available for the COVID-19 treatment are very limited. The most common measurements that enhance health condition and patients' viability are conservation fluid management, oxygen therapy, and antibiotics. Several therapeutic options have been developed or repurposed to prevent virus replication and/or modulate the immune response against virus infection. These options include various drugs that affect virus entry and membrane fusion, inhibit polymerase and protease activity, suppress the host pro-inflammatory cytokines, and utilize cell therapy approaches. KEY MESSAGES: In this review, we aimed to provide an up-to-date discussion on the current diagnostic options and therapeutic strategies used to control and manage COVID-19 in clinical and point-of-care settings.

Patient Satisfaction After Conservative Treatment for Burn Scars in Saudi Arabia.

Background Burn injury is a typical physical injury that occurs as a result of a thermal, electrical, or chemical stimulus. Burn injuries to the skin cause complicated issues, including scar marks, psychological impacts, and affect quality of life (QOL). The preferred treatment technique for burn scars is controversial, as attempts to control the contraction rate remain a challenge, often leading to a poor outcome. Thus, treating burn scar patients is one of the biggest challenges in reconstructive surgery. In this study, we aimed to assess the patients' perception of pain and QOL after conservative treatment for burn scars in Saudi Arabia. Methodology This was a cross-sectional study conducted on Saudi Arabian patients who underwent conservative treatment for their burn scars. Information was obtained using a self-reported questionnaire which was distributed online using Google Forms on several social media platforms. MS Excel was used for data entry, while SPSS version 23 was used for data analysis. Results We collected 523 responses to our questionnaire. Among respondents, 70.2% were aged between 18-29 years and 62.1% were single. Most burns were on the upper limbs (74.2%), and 78% of burns were caused by a thermal stimulus (exposure to heat). In terms of emotional status, most respondents did not report significant emotional issues related to their burn scars with a mean emotional score of 12.5 out of 24. Overall, burn scars did not affect the respondents' ability to work or independence in performing daily work. Regarding the impact of the burns on the patients' appearance, 29.4% of respondents reported that their scars bothered them significantly, 64.2% reported that their appearance never bothered them, and 11.5% reported that they sometimes tried to forget how their appearance had been changed. Conclusions We found that conservative treatment of burn scars is effective in controlling the pain associated with the burns and can improve the patient's ability to perform work and other daily activities. However, it did not completely improve the psychological distress associated with scars. Further investigations are required to understand the impact of adherence to conservative treatment for burn scars on the psychological status of patients.

Comparison of insulin-like growth factor-1 and sclerostin levels between premenopausal women with and without diabetes mellitus.

OBJECTIVES: This study assesses the serum levels of insulin-like growth factor-1 (IGF-1) and sclerostin as markers of decreased bone formation in premenopausal women with type 2 diabetes mellitus. METHODS: A cross-sectional study was conducted to measure serum levels of IGF-1 and sclerostin in 40 premenopausal women with and without diabetes mellitus using an enzyme-linked immunosorbent assay. The levels of IGF-1 and sclerostin were compared between the groups using the Mann Whitney test and unpaired t-test, respectively. RESULTS: The median IGF-1 serum levels were 40.60 ng/mL and 42.7 ng/mL in the diabetic and non-diabetic groups, respectively, with no significant difference. The serum levels of sclerostin were significantly higher in the diabetic group than in the non-diabetic group (132.1 pg/mL and 96.0 pg/mL, respectively; p < 0.001). CONCLUSION: The levels of sclerostin were significantly higher in premenopausal women with diabetes mellitus than in the non-diabetic group. Since sclerostin influences the differentiation and maturation of osteoblasts, serum sclerostin might potentially be useful as a marker of decreased bone formation in premenopausal women with diabetes.

Roll-to-Roll Manufactured Sensors for Nitroaromatic Organophosphorus Pesticides Detection.

A fully roll-to-roll manufactured electrochemical sensor with high sensing and manufacturing reproducibility has been developed for the detection of nitroaromatic organophosphorus pesticides (NOPPs). This sensor is based on a flexible, screen-printed silver electrode modified with a graphene nanoplatelet (GNP) coating and a zirconia (ZrO2) coating. The combination of the metal oxide and the 2-D material provided advantageous electrocatalytic activity toward NOPPs. Manufacturing, scanning electron microscopy-scanning transmission electron microscopy image analysis, electrochemical surface characterization, and detection studies illustrated high sensitivity, selectivity, and stability (∼89% current signal retention after 30 days) of the platform. The enzymeless sensor enabled rapid response time (10 min) and noncomplex detection of NOPPs through voltammetry methods. Furthermore, the proposed platform was highly group-sensitive toward NOPPs (e.g., methyl parathion (MP) and fenitrothion) with a detection limit as low as 1 µM (0.2 ppm). The sensor exhibited a linear correlation between MP concentration and current response in a range from 1 µM (0.2 ppm) to 20 µM (4.2 ppm) and from 20 to 50 µM with an R2 of 0.992 and 0.991, respectively. Broadly, this work showcases the first application of GNPs/ZrO2 complex on flexible silver screen-printed electrodes fabricated by entirely roll-to-roll manufacturing for the detection of NOPPs.

Addressing the global surge of COVID-19 cases: Insights from diagnostics, improved treatment strategies, vaccine development and application.

BACKGROUND AND AIM: As the rage of coronavirus disease 2019 (COVID-19) pandemic continues to spread globally, much effort is being directed to contain it through various efforts - genomic studies, drug discoveries, clinical trials, vaccine development, and the innovation of diagnostic techniques. However, some pertinent areas involving accurate and sensitive diagnostics, immunoglobulin specificity, evolution of mutant strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the drug combination strategy to combat it still require more attention. METHODS: This review critically examines the COVID-19 response and containment operations. It also addresses some standing challenges involving the areas of diagnostics, vaccine development and prospect, and treatment strategies in relation to antiviral drug treatment and immunotherapy. Designated set of keywords such as "SARS-CoV-2;" "coronavirus;" "severe acute respiratory syndrome coronavirus;" "repurposed;" "vaccination;" "containment;" "laboratory diagnostic;" "immunotherapy;" "antiviral;" "antiparasitic;" "antibiotic;" "antiprotozoal;" "antibody;" "anti-inflammatory;" "antitumor;" "corticosteroid;" "hypertensive drug;" "statin;" "supplement;" and "biological" along with "COVID-19" were inserted on electronic databases to retrieve articles and clinical trial information relevant to the study objectives. The search databases included ClinicalTrials.gov, NIH.gov, PubMed, Scinapse, CINAHL, Medline, Google Scholar, Academic Search Premier, SAGE, EBSCO Host, and Scopus. RELEVANCE FOR PATIENTS: The difficulties associated with SARS-CoV-2 rapid mutations are unceasingly evolving and re-evolving. These pose serious concerns and downplay the efficacy and effectiveness of the current pipeline antiviral drugs and vaccines. Entities encompassing immunotherapy, antiviral drug therapies, viral genomics, protein-protein interaction, and improved diagnostics as well as drug combination strategy against the emerging genetic variability of SARS-CoV-2 were critically appraised. This study suggests that robust collaborations in the development of more sensitive, rapid and accurate diagnostics, development of immunoglobulin specific agents and improved anti-viral treatment focus against multiple mutant genes of SARS-CoV-2 should be aggressively pursued for the overall benefits of COVID-19 patients.

The extreme drug resistance (XDR) Staphylococcus aureus strains among patients: A retrospective study.

The objective of the present work was to observe and profile various antibiotic resistant strains of Staphylococcus aureus and highlight the need for continuous surveillance. Data regarding antibiotic-resistant S. aureus strains isolated and identified at the Medical Microbiology Department, King Khalid Hospital, Riyadh was obtained. Bacterial isolates were collected from several sites of infections in patients and an evaluation of susceptibility were carried out using a fully automated Vitek2 system. Relative frequency (%), odds ratios and Ward's minimum variance were calculated. The results showed that wounds were a source of more than 40% of the S. aureus (MRSA) strains that have ability to resist methicillin, and more than 45% of the methicillin-susceptible S. aureus (non-MRSA) strains. 40% of the isolates were MRSA (N = 251), and all MRSA strains were sensitive to vancomycin, daptomycin, teicoplanin, tigecycline, nitrofurantoin, and itraconazole while all non-MRSA (N = 338) strains were sensitive to vancomycin, cefoxitin, daptomycin, gentamicin, oxacillin, teicoplanin, tigecycline, and mupirocin. Strength of association between antibiotic-resistant S. aureus strains and source of samples (site of infection) was established. The study concluded that S. aureus strains had developed resistance towards 20 (for non-MRSA) and 22 (for MRSA) of the antibiotics tested. All MRSA strains were non-sensitive to amoxicillin/clavulanate, ampicillin cefoxitin, cefazolin, imipenem, oxacillin, and penicillin.

Nanoscale Phenotypic Textures of Yersinia pestis Across Environmentally-Relevant Matrices.

The persistence of bacterial pathogens within environmental matrices plays an important role in the epidemiology of diseases, as well as impacts biosurveillance strategies. However, the adaptation potentials, mechanisms for survival, and ecological interactions of pathogenic bacteria such as Yersinia pestis are largely uncharacterized owing to the difficulty of profiling their phenotypic signatures. In this report, we describe studies on Y. pestis organisms cultured within soil matrices, which are among the most important reservoirs for their propagation. Morphological (nanoscale) and phenotypic analysis are presented at the single cell level conducted using Atomic Force Microscopy (AFM), coupled with biochemical profiles of bulk populations using Fatty Acid Methyl Ester Profiling (FAME). These studies are facilitated by a novel, customizable, 3D printed diffusion chamber that allows for control of the external environment and easy harvesting of cells. The results show that incubation within soil matrices lead to reduction of cell size and an increase in surface hydrophobicity. FAME profiles indicate shifts in unsaturated fatty acid compositions, while other fatty acid components of the phospholipid membrane or surface lipids remained consistent across culturing conditions, suggesting that phenotypic shifts may be driven by non-lipid components of Y. pestis.

Evaluating the efficiency of different natural clay sediments for the removal of chlortetracycline from aqueous solutions.

Natural clay sediments were collected from ten different localities in Saudi Arabia (S-1 from eastern, S-2 to S-4 from middle and S-5 to S-10 from western regions), characterized and evaluated for their efficiency towards chlortetracycline (CTC) removal from aqueous solutions. Sediment S-4 exhibited highest surface area (288.5 m2 g-1), followed by S-5, S-9, and S-1 (252.1, 249.6, and 110.4 m2 g-1, respectively). Sediments S-5, S-9, S-2, and S-4 showed the highest cation exchange capacities (CEC) (62.33, 56.54, 52.72, and 46.85 cmol kg-1, respectively). The pH range of 3.5-5.5 was optimum for the highest CTC removal. Freundlich model was best fitted to CTC sorption data (R2 = 0.96-0.99), followed by Dubinin-Radushkevich model (R2 = 0.89-0.97). The sediments S-4, S-5, and S-9 exhibited the highest CTC removal efficiency (98.80-99.05%), which could be due to higher smectite and kaolinite contents, CEC, surface area and layered structure. Post-sorption XRD patterns shown new peaks and peak shifts confirming the sorption of CTC. Electrostatic interactions, interlayer sorption and H-π bonding were the potential CTC sorption mechanisms. Therefore, natural clay sediments with high sorption capacities could efficiently remove CTC from contaminated aqueous media.

Prevalence of Escherichia coli strains resistance to antibiotics in wound infections and raw milk.

Antibiotic-resistant Escherichia coli strains including extended-spectrum ß-lactamase (ESBL) isolates are globally widespread in medical, food, and environmental sources. Some of these strains are considered the most pathogenic bacteria in humans. The present work examined the predominance of antibiotic resistance in E. coli strains in wound infections comparing with E. coli strains isolated from a raw milk as a potential source of those strains. The wound infections included abdomen, anus, arm, back, buttock, chest, foot, hand, head, leg, lung, mouth, neck, penis, thigh, toe, and vagina infections. In total, 161 and 153 isolates identified as E. coli were obtained from wound infections and raw milk, respectively. A Vitek 2 system innovated by bioMérieux, France was applied to perform the identification and susceptibility tests. The E. coli isolates that have ability to produce ESBL were detected by an ESBL panel and NO45 card (bioMérieux). Over half of the E. coli were from abdomen, back, and buttock wound infections. More than 50%of the E. coli isolates obtained from wound infections were resistant to cefazolin, ampicillin, cefuroxime, ciprofloxacin, mezlocillin, moxifloxacin, piperacillin, and tetracycline; 70% of the isolates from wound infections and 0% of the isolates from raw milk were E. coli isolates produced ESBL. The data showed that the strains resistance to multi-antibiotic and produced ESBL are more widespread among wound infections than in raw milk.

A meta-analysis comparing the risk of metastases in patients with rectal cancer and MRI-detected extramural vascular invasion (mrEMVI) vs mrEMVI-negative cases.

BACKGROUND: Pathological extramural vascular invasion (EMVI) is an independent prognostic factor in rectal cancer, but can also be identified on MRI-detected extramural vascular invasion (mrEMVI). We perform a meta-analysis to determine the risk of metastatic disease at presentation and after surgery in mrEMVI-positive patients compared with negative tumours. METHODS: Electronic databases were searched from January 1980 to March 2016. Conventional meta-analytical techniques were used to provide a summative outcome. Quality assessment of the studies was performed. RESULTS: Six articles reported on mrEMVI in 1262 patients. There were 403 patients in the mrEMVI-positive group and 859 patients in the mrEMVI-negative group. The combined prevalence of mrEMVI-positive tumours was 0.346(range=0.198-0.574). Patients with mrEMVI-positive tumours presented more frequently with metastases compared to mrEMVI-negative tumours (fixed effects model: odds ratio (OR)=5.68, 95% confidence interval (CI) (3.75, 8.61), z=8.21, df=2, P<0.001). Patients who were mrEMVI-positive developed metastases more frequently during follow-up (random effects model: OR=3.91, 95% CI (2.61, 5.86), z=6.63, df=5, P<0.001). CONCLUSIONS: MRI-detected extramural vascular invasion is prevalent in one-third of patients with rectal cancer. MRI-detected extramural vascular invasion is a poor prognostic factor as evidenced by the five-fold increased rate of synchronous metastases, and almost four-fold ongoing risk of developing metastases in follow-up after surgery.

Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans.

The virulence of Candida albicans is dependent upon fitness attributes as well as virulence factors. These attributes include robust stress responses and metabolic flexibility. The assimilation of carbon sources is important for growth and essential for the establishment of infections by C. albicans. Previous studies showed that the C. albicans ICL1 genes, which encode the glyoxylate cycle enzymes isocitratelyase are required for growth on non-fermentable carbon sources such as lactate and oleic acid and were repressed by 2% glucose. In contrast to S. cerevsiae, the enzyme CaIcl1 was not destabilised by glucose, resulting with its metabolite remaining at high levels. Further glucose addition has caused CaIcl1 to lose its signal and mechanisms that trigger destabilization in response to glucose. Another purpose of this study was to test the stability of the Icl1 enzyme in response to the dietary sugars, fructose, and galactose. In the present study, the ICL1 mRNAs expression was quantified using Quantitative Real Time PCR, whereby the stability of protein was measured and quantified using Western blot and phosphoimager, and the replacing and cloning of ICL1 ORF by gene recombination and ubiquitin binding was conducted via co-immuno-precipitation. Following an analogous experimental approach, the analysis was repeated using S. cerevisiaeas a control. Both galactose and fructose were found to trigger the degradation of the ICL1 transcript in C. albicans. The Icl1 enzyme was stable following galactose addition but was degraded in response to fructose. C. albicans Icl1 (CaIcl1) was also subjected to fructose-accelerated degradation when expressed in S. cerevisiae, indicating that, although it lacks a ubiquitination site, CaIcl1 is sensitive to fructose-accelerated protein degradation. The addition of an ubiquitination site to CaIcl1 resulted in this enzyme becoming sensitive to galactose-accelerated degradation and increases its rate of degradation in the presence of fructose. It can be concluded that ubiquitin-independent pathways of fructose-accelerated enzyme degradation exist in C. albicans.

Defining response to radiotherapy in rectal cancer using magnetic resonance imaging and histopathological scales.

AIM: To define good and poor regression using pathology and magnetic resonance imaging (MRI) regression scales after neo-adjuvant chemotherapy for rectal cancer. METHODS: A systematic review was performed on all studies up to December 2015, without language restriction, that were identified from MEDLINE, Cochrane Controlled Trials Register (1960-2015), and EMBASE (1991-2015). Searches were performed of article bibliographies and conference abstracts. MeSH and text words used included "tumour regression", "mrTRG", "poor response" and "colorectal cancers". Clinical studies using either MRI or histopathological tumour regression grade (TRG) scales to define good and poor responders were included in relation to outcomes [local recurrence (LR), distant recurrence (DR), disease-free survival (DFS), and overall survival (OS)]. There was no age restriction or stage of cancer restriction for patient inclusion. Data were extracted by two authors working independently and using pre-defined outcome measures. RESULTS: Quantitative data (prevalence) were extracted and analysed according to meta-analytical techniques using comprehensive meta-analysis. Qualitative data (LR, DR, DFS and OS) were presented as ranges. The overall proportion of poor responders after neo-adjuvant chemo-radiotherapy (CRT) was 37.7% (95%CI: 30.1-45.8). There were 19 different reported histopathological scales and one MRI regression scale (mrTRG). Clinical studies used nine and six histopathological scales for poor and good responders, respectively. All studies using MRI to define good and poor response used one scale. The most common histopathological definition for good response was the Mandard grades 1 and 2 or Dworak grades 3 and 4; Mandard 3, 4 and 5 and Dworak 0, 1 and 2 were used for poor response. For histopathological grades, the 5-year outcomes for poor responders were LR 3.4%-4.3%, DR 14.3%-20.3%, DFS 61.7%-68.1% and OS 60.7-69.1. Good pathological response 5-year outcomes were LR 0%-1.8%, DR 0%-11.6%, DFS 78.4%-86.7%, and OS 77.4%-88.2%. A poor response on MRI (mrTRG 4,5) resulted in 5-year LR 4%-29%, DR 9%, DFS 31%-59% and OS 27%-68%. The 5-year outcomes with a good response on MRI (mrTRG 1,2 and 3) were LR 1%-14%, DR 3%, DFS 64%-83% and OS 72%-90%. CONCLUSION: For histopathology regression assessment, Mandard 1, 2/Dworak 3, 4 should be used for good response and Mandard 3, 4, 5/Dworak 0, 1, 2 for poor response. MRI indicates good and poor response by mrTRG1-3 and mrTRG4-5, respectively.

Magnetic Resonance Tumor Regression Grade and Residual Mucosal Abnormality as Predictors for Pathological Complete Response in Rectal Cancer Postneoadjuvant Chemoradiotherapy.

BACKGROUND: Pathological complete response after chemoradiotherapy for rectal cancer occurs in 10% to 30% of patients. The best method to identify such patients remains unclear. Clinical assessment of residual mucosal abnormality is considered the most accurate method. In our institution, magnetic resonance tumor regression grade is performed as routine to assess response. OBJECTIVE: The purpose of this study was to compare the sensitivity of magnetic tumor regression grade against residual mucosal abnormality in detecting patients with a pathological complete response. DESIGN: Magnetic tumor regression grade scores from reported posttreatment MRI scans were documented. Magnetic tumor regression grade 1 to 3 was defined as likely to predict complete or near complete response. Gross appearances of the mucosa were derived from histopathology reports and used as a surrogate for clinical assessment (previously validated). Final histopathological staging was used to determine response. SETTINGS: The study was conducted at Royal Marsden National Health Service Trust, United Kingdom. PATIENTS: A total of 143 patients with rectal adenocarcinoma, diagnosed between September 1, 2009, and September 1, 2013, who received neoadjuvant chemoradiotherapy before curative surgery were included. MAIN OUTCOME MEASURES: The sensitivity of magnetic tumor regression grade and residual mucosal abnormality in detecting patients with pathological complete response were measured RESULTS: : Eighteen patients had a pathological complete response. Seventeen were detected using magnetic resonance tumor regression grade 1 to 3, with sensitivity 94% (95% CI, 0.74-0.99), and 10 were detected using residual mucosal abnormality, with sensitivity 62% (95% CI, 0.38-0.81). There was no statistical difference between the false positive rates for either method. Magnetic tumor regression grade identified 10 times more patients with a pathological complete response (diagnostic OR = 10.2 (95% CI, 1.30-73.73)) compared with clinical assessment with RMA. LIMITATIONS: Residual mucosal abnormality was used as a surrogate marker for endoscopic appearances. CONCLUSIONS: Most patients with rectal cancer who have a pathological complete response do not manifest a complete response at the mucosal level. Magnetic tumor regression grade is able to identify 10 times more patients than clinical assessment, with no significant compromise in the false positive rate.