ABL1-Directed Inhibitors for CML: Efficacy, Resistance and Future Perspectives.

The introduction of tyrosine kinase inhibitors (TKIs) directed against the catalytic activity of the ABL tyrosine kinase has considerably improved the outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease. Indeed, these individuals currently show a life-expectancy comparable to those of healthy subjects. Currently, five TKIs (imatinib, dasatinib, nilotinib, bosutinib and ponatinib) are approved for the treatment of CML and can be used as first, second or further lines of treatment according to disease risk scores, patient comorbidities and the presence of known TKI resistance mechanisms.

Analysis of the accuracy of actuation electronics in the laser interferometer space antenna pathfinder.

The Laser Interferometer Space Antenna Pathfinder (LPF) main observable, labeled Δg, is the differential force per unit mass acting on the two test masses under free fall conditions after the contribution of all non-gravitational forces has been compensated. At low frequencies, the differential force is compensated by an applied electrostatic actuation force, which then must be subtracted from the measured acceleration to obtain Δg. Any inaccuracy in the actuation force contaminates the residual acceleration.

Optimal Response in a Patient With CML Expressing E6A2 Fusion Transcript With Nilotinib Therapy: A Case Report.

Background/aim: The Philadelphia chromosome is considered the hallmark of chronic myeloid leukemia (CML). However, although most patients with CML are diagnosed with the e13a2 or e14a2 breakpoint cluster region (BCR)-Abelson 1 (ABL1) fusion transcripts, about 5% of them carry rare BCR-ABL1 fusion transcripts, such as e19a2, e8a2, e13a3, e14a3, e1a3 and e6a2. In particular, the e6a2 fusion transcript has been associated with clinically aggressive disease frequently presenting in accelerated or blast crisis phases; there is limited evidence on the efficacy of front-line second-generation tyrosine kinase inhibitors for this genotype.

Endometrial Cancer Risk Prediction According to Indication of Diagnostic Hysteroscopy in Post-Menopausal Women.

We conducted a prospective observational study investigating the clinical relevance of endometrial thickness (ET) and abnormal uterine bleeding (AUB) on endometrial cancer (EC) risk in a cohort of postmenopausal patients undergoing diagnostic hysteroscopy and endometrial biopsy. Patients were divided into two groups according to the indication of diagnostic hysteroscopy: ET_Group (asymptomatic patients with endometrial thickness ≥ 4 mm) and AUB_Group (patients with a history of abnormal uterine bleeding). We further divided the AUB_Group into two subgroups based on endometrial thickness (AUB_Subgroup1: ET < 4 mm; AUB_Subgroup2: ET ≥ 4 mm).

Impact of Hysteroscopic Metroplasty on Reproductive Outcomes of Women with a Dysmorphic Uterus and Recurrent Miscarriages: A Systematic Review and Meta-Analysis.

The aim of this systematic literature review and meta-analysis is to assess the impact of hysteroscopic metroplasty for dysmorphic uteri on reproductive outcomes in women with recurrent miscarriages. Available studies were identified through a PubMed, Scopus, and Cochrane search until June 2019. Live-birth rate, clinical pregnancy and miscarriage rate after hysteroscopic metroplasty was evaluated.

Endometrial scratching for infertility: The never-ending story.

Infertility, defined as the absence of spontaneous conception after 12 months of unprotected sexual intercourses, is a major public health issue. It is estimated that up to 15% of couples suffer from infertility and that most of them will refer for counselling to infertility specialists. Concurrently, the demands for assisted reproduction techniques are steadily increasing worldwide.

Association of 2-Year Progression Along the AREDS AMD Scale and Development of Late Age-Related Macular Degeneration or Loss of Visual Acuity: AREDS Report 41.

Importance: The Age-Related Eye Disease Study age-related macular degeneration (AREDS AMD) scale is designed to classify AMD severity. The present cohort study explored whether 2-year progression along this scale was useful for estimating the risk of future progression to late AMD or best-corrected visual acuity (BCVA) loss.

Objective: To assess whether 2-year progression along the AREDS AMD scale can be used to estimate the probability of long-term clinically meaningful outcome measures for clinical trials or epidemiologic studies.

Enhancing curcumin's solubility and antibiofilm activity silica surface modification.

Bacterial biofilms are microbial communities in which bacterial cells in sessile state are mechanically and chemically protected against foreign agents, thus enhancing antibiotic resistance. The delivery of active compounds to the inside of biofilms is often hindered due to the existence of the biofilm extracellular polymeric substances (EPS) and to the poor solubility of drugs and antibiotics. A possible strategy to overcome the EPS barrier is the incorporation of antimicrobial agents into a nanocarrier, able to penetrate the matrix and deliver the active substance to the cells.

Mutations in Serum Circulating Cell-Free Tumor DNA As Longitudinal Biomarker for High-Grade Serous Ovarian Cancer.

The aim of this study was to determine an optimal workflow to detect mutations in baseline and longitudinal serum cell free DNA (cfDNA) from high-grade serous ovarian carcinomas (HGSOC) patients and to define whether mutations are suitable as biomarker for disease. was investigated in tissue and archived serum from 20 HGSOC patients by a next-generation sequencing (NGS) workflow alone or combined with digital PCR (dPCR). AmpliSeq™-focused NGS panels and customized dPCR assays were used for tissue DNA and longitudinal cfDNAs, and Oncomine NGS panel with molecular barcoding was used for baseline cfDNAs.

Management of anxiety and pain perception in women undergoing office hysteroscopy: a systematic review.

Purpose: The aim of this review is to provide an overview of the literature about the perception and management of anxiety and pain in women undergoing an office hysteroscopic procedure.

Methods: We performed a systematic literature search in Embase, PubMed/MEDLINE, Cochrane Library and Web of Science for original studies written in English (registered in PROSPERO 2019-CRD42019132341), using the terms 'hysteroscopy' AND 'pain' AND 'anxiety' published up to January 2019. Only original articles (randomized, observational and retrospective studies) about management of anxiety and pain related to the hysteroscopic procedure were considered eligible.

Effect of intravenous iron replacement therapy on exercise capacity in iron deficient anemic patients after cardiac surgery.

Iron deficiency (ID) is recognized as an important comorbidity in patients undergoing cardiac surgery; however, it still remains under-diagnosed and under-treated in clinical practice. This study aims at comparing efficacy and the effects on exercise capacity of intravenous ferric carboxymaltose (FCM) versus ferric gluconate (FG) in patients with ID anemia (IDA) resulting from cardiac surgery. We retrospectively analyzed data from our records of in-hospital patients with IDA after cardiac surgery undergoing cardiac rehabilitation.

Targeting BCL-2 as a Therapeutic Strategy for Primary -positive B-ALL Cells.

Background/aim: Philadelphia-positive acute lymphoblastic leukemia (Ph B-ALL) is caused by the malignant transformation of lymphoid cells induced by BCR-ABL1 constitutive catalytic activity. BCR-ABL1 tyrosine kinase inhibitors (TKIs) are effective against chronic myeloid leukemia (CML) cells, inducing durable hematological, cytogenetic and molecular responses. However, in Ph B-ALL - as in CML progressing to blast crisis - TKIs fail to maintain disease remission.

Ulipristal Acetate Before Hysteroscopic Myomectomy: A Systematic Review.

Importance: Uterine leiomyomas, also referred to as myomas or fibroids, are the most common benign tumors of the reproductive tract. Ulipristal acetate (UPA) is an active selective progesterone receptor modulator used as preoperative treatment for uterine myomas.

Purpose: The aim of this review is to provide an overview of the literature about the effects of UPA administration before hysteroscopic myomectomy.

Updates in office hysteroscopy: a practical decalogue to perform a correct procedure.

Nowadays, hysteroscopy is the gold standard for the diagnosis and treatment of intrauterine pathologies as it represents a safe and minimally invasive procedure that allows the visualization of the entire uterine cavity. Numerous technological innovations have occurred over the past few years, contributing to the development and widespread use of this technique. In particular, the new small-diameter hysteroscopes are equipped with an operating channel in which different mechanical instruments can be inserted, and they allow not only to examine the cervical canal and uterine cavity but also to perform biopsies or treat benign diseases in a relatively short time without anesthesia and in an outpatient setting.

Fallopian tubal obstruction is associated with increased pain experienced during office hysteroscopy: a retrospective study.

This study aimed at evaluating the pain experienced during office hysteroscopy, with selective tubal cannulation and chromopertubation, by women with and without tubal obstruction in order to determine if such condition would be associated with increased pain during the examination. Women with a history of infertility underwent in-office hysteroscopy with selective chromopertubation using a continuous flow office hysteroscope with a 5 Fr operating channel fitted with a 4 Fr catheter for the injection of methylene blue dye. Experienced pain was recorded on a Visual Analog Scale (VAS) during diagnostic hysteroscopy after access to the uterine cavity.

From hysteroscopy to laparoendoscopic surgery: what is the best surgical approach for symptomatic isthmocele? A systematic review and meta-analysis.

Purpose: To investigate the effectiveness and risks of different surgical therapies for isthmocele in symptomatic women with abnormal uterine bleeding, infertility, or for the prevention of obstetric complications, considering safety and surgical complications.

Methods: PubMed/MEDLINE, Scopus, Embase, Science Direct, and Cochrane Library were systematically searched (n° CRD4201912035) for original articles on the surgical treatment of isthmocele published between 1950 and 2018. Data synthesis was completed using MedCalc 16.

Vilaprisan, a New Selective Progesterone Receptor Modulator in Uterine Fibroid Pharmacotherapy-Will it Really be a Breakthrough?

Background: Vilaprisan (VPR) is a new orally available selective progesterone receptor modulator (SPRM), with anti-proliferative activity against uterine fibroids (UFs). It definitively causes suppression of ovulation and inhibition of proliferation of endometrial, myometrial and UF cells.

Purpose: This review aims to summarize current knowledge on VPR from all studies, including clinical trials, conducted to date and to contextualize the potential role of VPR in future medical regimens for the treatment of UFs.

Innovations in hysteroscopic surgery: expanding the meaning of "in-office".

Surgical innovations in hysteroscopic surgery have radically changed the way of treating intrauterine pathologies, throughout the advent of the 'see-and-treat' philosophy, which transferred the advantages of inpatient surgery to the office setting. However, in-office operative hysteroscopy was mainly limited to minor pathology as a supplement to its diagnosis, whereas commonly larger abnormalities were left to be treated in the operating room. Nowadays, pre-surgical assessment of uterine pathology is based on modern ultrasound evaluation and the evolving role of in-office hysteroscopy as a well-planned treatment modality for larger lesions and more complex procedures.

Comparison of cerebellomedullary and lumbar cerebrospinal fluid analysis in dogs with neurological disease.

Background: Cerebrospinal fluid (CSF) analysis aids in categorizing underlying disease processes in patients with neurologic disease. Convention suggests that CSF should be collected caudal to the lesion. However, little evidence exists to justify this assertion.

Preoperative Treatment with Ulipristal Acetate before Outpatient Hysteroscopic Myomectomy.

Introduction: Nowadays, the resection of submucosal myomas is usually performed by hysteroscopy. No previous study has investigated the use of preoperative hormonal therapy before outpatient hysteroscopic myomectomy.

Objective: To compare the usefulness of 3-month preoperative treatment with ulipristal acetate (UPA) before outpatient hysteroscopic myomectomy in patients with FIGO (International Federation of Gynecology and Obstetrics) type 0-1 myomas.

Comparison of Serum Trace Nutrient Concentrations in Epileptics Compared to Healthy Dogs.

Idiopathic epilepsy (IE) is a common cause of seizures in dogs. There are several investigations regarding serum concentrations of trace nutrients, including copper, selenium, zinc, manganese, and iron in human epileptics and animal models. However, research of this nature in dogs with epilepsy is lacking.

Potential toxic elements in groundwater and their health risk assessment in drinking water of Limpopo National Park, Gaza Province, Southern Mozambique.

Concentrations of trace elements in drinking water affect its safety and acceptability for use. Potentially toxic element (PTE) contaminations are considered extremely hazardous because of toxicity, persistence, and bioaccumulative behaviour. Many areas in the Southern African Development Community are data poor and have poor accessibility.

Reproducibility of Full-field Electroretinogram Measurements in Birdshot Chorioretinopathy Patients: An Intra- and Inter-visit Analysis.

: Aims to determine the variability of ffERG measurements in patients with clinically stable birdshot chorioretinopathy (BCR).: Repeatability coefficients (RC) of ffERG amplitudes and implicit times were calculated from 11 BCR patients. Jackknife resampling estimated 95% confidence intervals of each ERG parameter's RC and the percentage change explained by variability alone was calculated.