Draft genome sequence of novel Candidatus Ornithobacterium hominis carrying antimicrobial resistance genes in Egypt.

BACKGROUND: Candidatus Ornithobacterium hominis (O. hominis), which was identified in nasopharyngeal swabs from Egypt, has been associated with respiratory disorders in humans. O. hominis, a recently identified member of the Flavobacteriaceae family, belongs to the largest family within the Bacteroidetes phylum. This family includes hundreds of species and 90 genera, including major human pathogens such as Capnocytophaga canimorsus and Elizabethkingia meningoseptica. Herein, we presented two draft genome assemblies of O. hominis that were extracted from metagenomic data using the Illumina sequencing method. The alignment of reads against the O. hominis genome was accomplished using BLASTN, and the reads with significant hits were extracted using Seqtk and assembled using SPAdes. The primary goal of this study was to obtain a more profound understanding of the genomic landscape of O. hominis, with an emphasis on identifying the associated virulence, antimicrobial genes, and distinct defense mechanisms to shed light on the potential role of O. hominis in human respiratory infections. RESULTS: The genome size was estimated to be 1.84 Mb, including 1,931,660 base pairs (bp), with 1,837 predicted coding regions and a G+C content of 35.62%. Genes encoding gliding motility, antibiotic resistance (20 genes), and the toxA gene were all included in the genome assembly. Gliding motility lipoproteins (GldD, GldJ, GldN, and GldH) and the gliding motility-associated ABC transporter substrate-binding protein, which acts as a crucial virulence mechanism in Flavobacterium species, were identified. The genome contained unique genes encoding proteins, such as the ParE1 toxin that defend against the actions of quinolone and other antibiotics. The cobalt-zinc-cadmium resistance gene encoding the protein CzcB, which is necessary for metal resistance, urease regulation, and colonization, was also detected. Several multidrug resistance genes encoding proteins were identified, such as MexB, MdtK, YheI, and VanC. CONCLUSION: Our study focused on identifying virulence factors, and antimicrobial resistance genes present in the core genome of O. hominis. These findings provide valuable insights into the potential pathogenicity and antibiotic susceptibility of O. hominis.

Large Ascites in a Cirrhotic Patient Reveal an Isolated and Late Metastasis of Ductal Breast Cancer: A Case Study.

Breast cancer is the most prevalent cancer in women worldwide, and its prevalence has increased since the introduction of screening programs. Most cases are discovered at an early stage; however, despite effective treatment, some cases progress to metastasis. The most common breast cancer metastatic locations are the bone, liver, and lungs. Ascites malignant due to peritoneal involvement is a rare manifestation of metastatic breast cancer. After 8 years of well-controlled breast cancer, we report a 54-year-old woman who presents with malignant ascites and is known to have cirrhosis of the liver.

Acute Exfoliative Dermatitis/Erythroderma Secondary to Gliclazide.

Erythroderma is a general term used to describe severe, intense skin inflammation. The condition is also known as exfoliative dermatitis when it is associated with exfoliation. Erythroderma has many causes, such as adverse drug eruption, dermatitis, psoriasis, pityriasis rubra pilaris, immunobullous disease, cutaneous T-cell lymphoma (Sézary syndrome), underlying systemic malignancy, graft versus host disease, and HIV infection. Many medications can cause erythroderma, including antibiotics, antiepileptics, angiotensin-converting enzyme (ACE) inhibitors, and sulfonamides. Here, we report a rare case of erythroderma secondary to gliclazide, an oral antidiabetic. This presentation is rare, as we found only one case report of gliclazide causing erythroderma in the literature. Erythroderma is considered a medical emergency requiring immediate diagnosis and prompt management; therefore, early intervention should start on suspicion without waiting for dermatologist confirmation, as this will significantly reduce the mortality and morbidity of this potentially life-threatening emergency.

Effect of Photobiomodulation on the Depth of Local Anesthesia during Endodontic Treatment of Teeth with Symptomatic Irreversible Pulpitis.

AIM: To determine whether photobiomodulation (PBM) therapy could increase the depth of analgesia during endodontic therapy of teeth affected with symptomatic irreversible pulpitis. MATERIALS AND METHODS: Forty-nine patients with symptomatic irreversible pulpitis were randomized into two groups. In the laser group, before administering anesthesia, the lower molars' crowns were continuously treated with a diode laser (980 nm) for 20 s with a low-level laser tip in the buccal aspect close to the gingival margin. While the teeth of the second group who was blinded to the type of treatment received placebo treatment wherein the laser device was switched off. The visual analogue scale (VAS) was used to assess pain in both groups before the endodontic procedure, during dentin cutting, and at dropping pulp, wherein, the success was defined as no or mild pain. The Chi-square and independent sample t-tests were used to assess the data. RESULTS: During dentin cutting and pulp dropping, the group receiving the laser therapy presented with less mean pain score than the placebo group which was statistically significant. Additionally, it was observed that the need for supplementary injection was less frequent in the laser-treated group than in the placebo group (p = 0.01). CONCLUSION: The irradiation by diode laser (980 nm) prior to administration of local anesthesia appears to be useful in minimizing discomfort and additional injection during root canal therapy (RCT). CLINICAL SIGNIFICANCE: Pain management is essential for providing the best possible treatment to patients before, during, and after endodontic therapy. Adequate pain control during treatment also aids in reducing postoperative discomfort. This implies the need for additional methods to reduce discomfort during endodontic treatment; hence, adjuncts are crucial to achieving this goal. Photobiomodulation may be used as an adjuvant to reduce discomfort and supplementary injections during RCT.

Prevalence of preoperative anxiety among hospitalized patients in a developing country: a study of associated factors.

BACKGROUND: Preoperative anxiety is a health concern among patients scheduled for surgical interventions. Little is known about the prevalence of preoperative anxiety among patients in different healthcare systems of developing countries. This study was conducted to determine the prevalence of preoperative anxiety among patients undergoing surgery in Palestine. Another objective was to identify the factors associated with preoperative anxiety. METHODS: This study was conducted in a cross-sectional descriptive design. Patients scheduled for surgical interventions were interviewed using an interviewer-administered questionnaire. The questionnaire collected the demographic, clinical, and surgical variables of the patients. The questionnaire also contained the Amsterdam preoperative anxiety and information scale (APAIS), and a short version of the Spielberger state-trait anxiety inventory (STAIS-5/STAIT-5). RESULT: A total of 280 patients were included. The mean APAIS total score was 13.6 ± 5.9, the mean APAIS anxiety domain score was 8.3 ± 4.3, and the mean APAIS need for information domain was 1.6 ± 0.50. Of the patients, 76 (27.1%) had high anxiety and 160 (57.1%) expressed a high need for information. The higher APAIS anxiety scores were predicted by being female, having chronic diseases, being scheduled to be operated on within 24 h, and having experienced surgical complications. The mean STAIS-5 score was 10.0 ± 4.2 and the mean STAIT-5 was 10.3 ± 3.8. Of the patients, 140 (50.0%) had high state anxiety and 56 (20.0%) had high trait anxiety. Higher STAIS-5 scores were predicted by being female, younger than 42 years, and scheduled to be operated on within 24 h. Higher STAIT-5 scores were predicted by being female. A positive correlation was identified between APAIS total, APAIS anxiety, APAIS need for information, STAIS-5, and STAIT-5 scores. CONCLUSION: Preoperative anxiety was prevalent among patients scheduled for surgical operations in Palestinian hospitals. Anesthesiologists and other providers of perioperative care should screen preoperative patients who are female, have chronic diseases, are scheduled to be operated on within 24 h, and having had experienced surgical complications for preoperative anxiety. More studies are still needed to investigate the effects of the implemented measures on the prevalence of preoperative anxiety.

Low-Dose Chest CT Protocols for Imaging COVID-19 Pneumonia: Technique Parameters and Radiation Dose.

Chest computed tomography (CT) plays a vital role in the early diagnosis, treatment, and follow-up of COVID-19 pneumonia during the pandemic. However, this raises concerns about excessive exposure to ionizing radiation. This study aimed to survey radiation doses in low-dose chest CT (LDCT) and ultra-low-dose chest CT (ULD) protocols used for imaging COVID-19 pneumonia relative to standard CT (STD) protocols so that the best possible practice and dose reduction techniques could be recommended. A total of 564 articles were identified by searching major scientific databases, including ISI Web of Science, Scopus, and PubMed. After evaluating the content and applying the inclusion criteria to technical factors and radiation dose metrics relevant to the LDCT protocols used for imaging COVID-19 patients, data from ten articles were extracted and analyzed. Technique factors that affect the application of LDCT and ULD are discussed, including tube current (mA), peak tube voltage (kVp), pitch factor, and iterative reconstruction (IR) algorithms. The CTDIvol values for the STD, LDCT, and ULD chest CT protocols ranged from 2.79-13.2 mGy, 0.90-4.40 mGy, and 0.20-0.28 mGy, respectively. The effective dose (ED) values for STD, LDCT, and ULD chest CT protocols ranged from 1.66-6.60 mSv, 0.50-0.80 mGy, and 0.39-0.64 mSv, respectively. Compared with the standard (STD), LDCT reduced the dose reduction by a factor of 2-4, whereas ULD reduced the dose reduction by a factor of 8-13. These dose reductions were achieved by applying scan parameters and techniques such as iterative reconstructions, ultra-long pitches, and fast spectral shaping with a tin filter. Using LDCT, the cumulative radiation dose of serial CT examinations during the acute period of COVID-19 may have been inferior or equivalent to that of conventional CT.

The genetic profile and molecular subtypes of human pseudomyxoma peritonei and appendiceal mucinous neoplasms: a systematic review.

Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low as 48%. PMP is most commonly caused by appendiceal mucinous neoplasms (AMN), and understanding their genetic biology and pathogenicity may allow for the development of better novel systemic treatments to target key deleterious mutations and the implicated pathways. The primary aim of this systematic review was to identify the genetic profile of histologically confirmed human PMP or AMN samples. The secondary aim was to identify whether genetic marks could be used to predict patient survival. Ovid EMBASE, Ovid MEDLINE, PubMed, and Web of Science were searched to identify studies investigating the genetic profile of histologically-confirmed human PMP or AMN samples. We review findings of 46 studies totalling 2181 tumour samples. The most frequently identified somatic gene mutations in patients with PMP included KRAS (38-100%), GNAS (17-100%), and TP53 (5-23%); however, there were conflicting results of their effect on survival. Three studies identified molecular subtypes based on gene expression profiles classifying patients into oncogene-enriched, immune-enriched, and mixed molecular subtypes with prognostic value. This review summarises the current literature surrounding genetic aberrations in PMP and AMNs and their potential utility for targeted therapy. Given the recent advances in clinical trials to directly target KRAS and GNAS mutations in other cancers, we propose a rationale to explore these mutations in future pre-clinical studies in PMP with a view for a future clinical trial.

Antioxidative and Cytoprotective Efficacy of Ethanolic Extracted Cranberry Pomace against Salmonella Enteritidis Infection in Chicken Liver Cells.

Salmonella enterica serovar Enteritidis is a globally significant zoonotic foodborne pathogen. Chicken liver is a vital organ that has been recently implicated in several reported human salmonellosis outbreaks in the U.S. One promising strategy for reducing Salmonella in chickens could be through supplementation with natural antimicrobial additives. Ethanolic extracted cranberry pomace (CPOH) is an excellent source of bioactive polyphenolic compounds with antioxidant and antimicrobial activities. However, the protective effect of CPOH against S. Enteritidis-induced chicken hepatic cell damage remains unclear. In this study, we used a chicken hepatoma cell (LMH) infection model to investigate the protective effects and potential mechanisms of CPOH. CPOH increased the viability of S. Enteritidis-infected LMH cells. Furthermore, CPOH reduced the adhesion and invasion of S. Enteritidis to LMH cells. CPOH downregulated the expression of Rho GTPase genes that are essential for Salmonella's entry into LMH cells. Additionally, the expression of antioxidant regulatory genes, such as Nrf2, HO-1, Txn, and Gclc, was increased. Our data show that CPOH effectively protected LMH cells from cell damage through the inhibition of S. Enteritidis adhesion and invasion, as well as the induction of the expression of master antioxidant genes. These findings offer opportunities to develop sustainable, safe, and economic strategies to reduce the colonization and pathogenesis of Salmonella.

Typical effective dose values from diagnostic and interventional radiology.

Effective dose (E) in medical procedures is of practical value for comparing doses from different types of procedures which is not possible with the different measurable dose quantities. In this survey we estimated and compared the values of E in 12 medical imaging procedures. The mean E for conventional X-ray in mSv were ranged between 0.01 for skull lateral to 0.5 for abdominal while the mean E for cardiac interventional radiology in mSv was up to 16 for percutaneous transluminal coronary angioplasty (PTCA). For dental radiology the mean E in µSv was 1.2 for intraoral and 10 for panoramic. In mammography the mean E was 0.5 mSv. Compared with the literature, chest postero-anterior (PA), lumbar spine AP, PTCA and mammography procedures had shown larger E values. The obtained results can help in justification of techniques.

Circulating microRNAs and Clinicopathological Findings of Papillary Thyroid Cancer: A Systematic Review.

BACKGROUND/AIM: Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a rising incidence. There is a need for a non-invasive preoperative test to enable better patient counselling. The aim of this systematic review was to investigate the potential role of circulating microRNAs (miRNAs) in the diagnosis and prognosis of PTC. MATERIALS AND METHODS: A systematic literature search was performed using MEDLINE, Cochrane, and Scopus databases (last search date was December 1, 2021). Studies investigating the expression of miRNAs in the serum or plasma of patients with PTC were deemed eligible for inclusion. RESULTS: Among the 1,533 screened studies, 39 studies met the inclusion criteria. In total, 108 miRNAs candidates were identified in the serum, plasma, or exosomes of patients suffering from PTC. Furthermore, association of circulating miRNAs with thyroid cancer-specific clinicopathological features, such as tumor size (13 miRNAs), location (3 miRNAs), extrathyroidal extension (9 miRNAs), pre- vs. postoperative period (31 miRNAs), lymph node metastasis (17 miRNAs), TNM stage (9 miRNAs), BRAF V600E mutation (6 miRNAs), serum thyroglobulin levels (2 miRNAs), 131I avid metastases (13 miRNAs), and tumor recurrence (2 miRNAs) was also depicted in this study. CONCLUSION: MiRNAs provide a potentially promising role in the diagnosis and prognosis of PTC. There is a correlation between miRNA expression profiles and specific clinicopathological features of PTC. However, to enable their use in clinical practice, further clinical studies are required to validate the predictive value and utility of miRNAs as biomarkers.

Simple Gene Knockdown in Endothelial Cells Using Short Interfering RNA Oligonucleotides.

Cell transfection using short interfering RNAs (siRNAs) is a widely used technique to perform loss of function studies by "knocking down" genes of interest. Oftentimes, primary cells can be difficult to transfect, but here we provide a simple and robust method using cultured endothelial cells and routine transfection reagents. Knockdown studies can be used to complement overexpression studies and validate biochemical pathway analysis, as well as functional assays. The enclosed protocol will compliment other in vitro assays detailed in this edition.

Transcription Factor Control of Lymphatic Quiescence and Maturation of Lymphatic Neovessels in Development and Physiology.

The lymphatic system is a vascular system comprising modified lymphatic endothelial cells, lymph nodes and other lymphoid organs. The system has diverse, but critical functions in both physiology and pathology, and forms an interface between the blood vascular and immune system. It is increasingly evident that remodelling of the lymphatic system occurs alongside remodelling of the blood microvascular system, which is now considered a hallmark of most pathological conditions as well as being critical for normal development. Much attention has focussed on how the blood endothelium undergoes phenotypic switching in development and disease, resulting in over two decades of research to probe the mechanisms underlying the resulting heterogeneity. The lymphatic system has received less attention, and consequently there are fewer descriptions of functional and molecular heterogeneity, but differential transcription factor activity is likely an important control mechanism. Here we introduce and discuss significant transcription factors of relevance to coordinating cellular responses during lymphatic remodelling as the lymphatic endothelium dynamically changes from quiescence to actively remodelling.

NATIONAL DIAGNOSTIC REFERENCE LEVELS AND ACHIEVABLE DOSES FOR STANDARD CT EXAMINATIONS IN SUDAN.

Radiation doses were determined to propose national diagnostic reference levels (NDRLs) and achievable doses (ADs) for computed tomography (CT) examinations in Sudan. Doses were estimated from retrospectively collected scan parameters for 1336 CT examinations of adult patients from 14 Sudanese hospitals using CT Expo 2.5 software. ADs and NDRLs were set at the 50th and 75th percentile of the hospital median dose distribution, respectively. The proposed CTDIvol (mGy) ADs ranged from: 10 (chest) to 64 (head), and that of the dose-length product (DLP; mGy.cm) ranged from 366 (chest) to 1225 (head). The proposed CTDIvol (mGy) NDRLs ranged from 15 kidney-ureter-bladder (KUB) to 79 (head), whereas that of the DLP (mGy.cm) ranged from 690 (chest) to 1490 (head). Current doses fell within the upper range of the doses presented in the literature emphasizing the need for implementation of the current ADs and NDRLs for CT to enhance patient protection and dose optimization in Sudan.

Fabrication, Modification, and Characterization of Lignin-Based Electrospun Fibers Derived from Distinctive Biomass Sources.

From the environmental point of view, there is high demand for the preparation of polymeric materials for various applications from renewable and/or waste sources. New lignin-based spun fibers were produced, characterized, and probed for use in methylene blue (MB) dye removal in this study. The lignin was extracted from palm fronds (PF) and banana bunch (BB) feedstock using catalytic organosolv treatment. Different polymer concentrations of either a plasticized blend of renewable polymers such as polylactic acid/polyhydroxybutyrate blend (PLA-PHB-ATBC) or polyethylene terephthalate (PET) as a potential waste material were used as matrices to generate lignin-based fibers by the electrospinning technique. The samples with the best fiber morphologies were further modified after iodine handling to ameliorate and expedite the thermostabilization process. To investigate the adsorption of MB dye from aqueous solution, two approaches of fiber modification were utilized. First, electrospun fibers were carbonized at 500 °C with aim of generating lignin-based carbon fibers with a smooth appearance. The second method used an in situ oxidative chemical polymerization of m-toluidine monomer to modify electrospun fibers, which were then nominated by hybrid composites. SEM, TGA, FT-IR, BET, elemental analysis, and tensile measurements were employed to evaluate the composition, morphology, and characteristics of manufactured fibers. The hybrid composite formed from an OBBL/PET fiber mat has been shown to be a promising adsorbent material with a capacity of 9 mg/g for MB dye removal.

Pregnancy-associated breast cancer: evaluating maternal and foetal outcomes. A national study.

PURPOSE: Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during the gestational period (gp-PABC) or in the first postpartum year (pp-PABC). Despite its infrequent occurrence, the incidence of PABC appears to be rising due to the increasing propensity for women to delay childbirth. We have established the first retrospective registry study of PABC in Ireland to examine specific clinicopathological characteristics, treatments, and maternal and foetal outcomes. METHODS: This was a national, multi-site, retrospective observational study, including PABC patients treated in 12 oncology institutions from August 2001 to January 2020. Data extracted included information on patient demographics, tumour biology, staging, treatments, and maternal/foetal outcomes. Survival data for an age-matched breast cancer population over a similar time period was obtained from the National Cancer Registry of Ireland (NCRI). Standard biostatistical methods were used for analyses. RESULTS: We identified 155 patients-71 (46%) were gp-PABC and 84 (54%) were pp-PABC. The median age was 36 years. Forty-four patients (28%) presented with Stage III disease and 25 (16%) had metastatic disease at diagnosis. High rates of triple-negative (25%) and HER2+ (30%) breast cancer were observed. We observed an inferior 5-year overall survival (OS) rate in our PABC cohort compared to an age-matched breast cancer population in both Stage I-III (77.6% vs 90.9%) and Stage IV disease (18% vs 38.3%). There was a low rate (3%) of foetal complications. CONCLUSION: PABC patients may have poorer survival outcomes. Further prospective data are needed to optimise management of these patients.

Molecular profiling reveals a hypoxia signature in breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently characterized T-cell malignancy that has raised significant patient safety concerns and led to worldwide impact on the implants used and clinical management of patients undergoing reconstructive or cosmetic breast surgery. Molecular signatures distinguishing BIA-ALCL from other ALCLs have not been fully elucidated and classification of BIA-ALCL as a WHO entity remains provisional. We performed RNA sequencing and gene set enrichment analysis comparing BIA-ALCLs to non-BIA-ALCLs and identified dramatic upregulation of hypoxia signaling genes including the hypoxia-associated biomarker CA9 (carbonic anyhydrase-9). Immunohistochemistry validated CA9 expression in all BIA-ALCLs, with only minimal expression in non-BIA-ALCLs. Growth induction in BIA-ALCL-derived cell lines cultured under hypoxic conditions was proportional to up-regulation of CA9 expression, and RNA sequencing demonstrated induction of the same gene signature observed in BIA-ALCL tissue samples compared to non-BIA-ALCLs. CA9 silencing blocked hypoxia-induced BIA-ALCL cell growth and cell cycle-associated gene expression, whereas CA9 overexpression in BIA-ALCL cells promoted growth in a xenograft mouse model. Furthermore, CA9 was secreted into BIA-ALCL cell line supernatants and was markedly elevated in human BIA-ALCL seroma samples. Finally, serum CA9 concentrations in mice bearing BIA-ALCL xenografts were significantly elevated compared to control serum. Together, these findings characterize BIA-ALCL as a hypoxia-associated neoplasm, likely attributable to the unique microenvironment in which it arises. These data support classification of BIA-ALCL as a distinct entity and uncover opportunities for investigating hypoxia-related proteins such as CA9 as novel biomarkers and therapeutic targets in this disease.

Hypothyroidism in restless legs syndrome.

The diurnal nature of restless legs syndrome (RLS) and its response to dopamine hint that hormones are central in RLS pathophysiology. Hypothyroidism has been linked to RLS, but studies are limited. This study's objective is to determine whether RLS is more prevalent in persons with hypothyroidism and whether hypothyroidism is more prevalent in RLS sufferers. Persons with hypothyroidism and controls were recruited through an on-line registry of potential research participants. RLS was assessed using the Cambridge-Hopkins questionnaire. RLS persons and controls were recruited through RLS Foundation and on-line registry advertisements and assessed for hypothyroidism by self-report. The International RLS Study Group Severity Scale assessed RLS severity; 266 hypothyroid subjects and 321 controls were comparable in age (52.3 ± 13.4 versus 53.9 ± 11.7 years; p = .14) and gender (91.7% versus 91.3% women; p = .85), as were 354 RLS and 313 controls (59.1 ± 13.2 versus 58.2 ± 13.6 years; p = .41; 80.8% versus 78.3% women; p = .42). Hypothyroid participants versus controls had a significantly higher prevalence of RLS (14.3% versus 8.1%; p = .02). RLS participants versus controls had a significantly higher prevalence of hypothyroidism (22.3% versus. 13.8%; p = .005). RLS severity was similar in persons with and without hypothyroidism. Among 73 persons with RLS and hypothyroidism, 14 previously were hyperthyroid versus 0 of 37 persons with hypothyroidism alone (p = .004). RLS prevalence is increased in individuals with hypothyroidism; hypothyroidism prevalence is increased in individuals with RLS. Persons with hypothyroidism and RLS are significantly more likely than those with hypothyroidism alone to have had hyperthyroidism prior to hypothyroidism. Associations between RLS and thyroid disease may shed light on complex biological mechanisms underlying RLS.

PROPOSED NATIONAL DIAGNOSTIC REFERENCE LEVELS FOR STANDARD RADIOGRAPHIC X-RAY PROCEDURES IN SUDAN.

This study aimed to calculate patient radiation doses for adults during the seven most commonly performed conventional X-ray procedures, and to propose national diagnostic reference levels (DRLs). A representative sample of patients from 29 hospitals was included. The entrance surface air kerma (ESAK) was calculated by measuring X-ray tube output and the corresponding technical and exposure factors for each patient. Third-quartile values of the mean ESAK distributions were proposed as DRL values. The DRLs in mGy were as follows: 0.6 for chest postero-anterior (PA), 3.5 for skull AP, 1.7 for skull lateral (LAT), 2.7 for abdominal, 2.6 for pelvic AP, 3.7 for lumbar spine AP and 8 for lumbar spine LAT. Compared with literature, the maximum percentages increase were in chest PA (329%) and skull AP (187%). Since the suggested DRL for chest PA was higher than literature values, dose optimization and a review of its value is recommended.

Targeting epigenetic regulators in the treatment of T-cell lymphoma.

Introduction: T-cell lymphomas represent a broad group of malignant T-cell neoplasms with marked molecular, clinical, and biologic heterogeneity. Survival rates after conventional chemotherapy regimens are poor for most subtypes and new therapies are needed. Rapidly expanding knowledge in the field of epigenomics and the development of an increasing number of epigenetic-modifying agents have created new opportunities for epigenetic therapies for patients with this complex group of diseases.Areas covered: The present review summarizes current knowledge on epigenetic alterations in T-cell lymphomas, availability, and mechanisms of action of epigenetic-modifying agents, results of clinical trials of epigenetic therapies in T-cell lymphomas, status of FDA approval, and biomarker approaches to guide therapy. Promising future directions are discussed.Expertopinion: Mutations in epigenetic-modifying genes are among the most common genetic alterations in T-cell lymphomas, highlighting the potential for epigenetic therapies to improve management of this group of diseases. Single-agent efficacy is well documented, leading to FDA approval for several indications, but overall response rates and durability of responses remain modest. Critical next steps for the field include optimizing combination therapies that incorporate epigenetic-modifying agents and developing predictive biomarkers that help guide patient and drug selection.