Molecular Pathogenesis of Chronic Myelomonocytic Leukemia and Potential Molecular Targets for Treatment Approaches.

Numerous examples in oncology have shown that better understanding the pathophysiology of a malignancy may be followed by the development of targeted treatment concepts with higher efficacy and lower toxicity as compared to unspecific treatment. The pathophysiology of chronic myelomonocytic leukemia (CMML) is heterogenous and complex but applying different research technologies have yielded a better and more comprehensive understanding of this disease. At the moment treatment for CMML is largely restricted to the unspecific use of cytotoxic drugs and hypomethylating agents (HMA).

Perioperative sedation requirements of infants aged 0 to 3 months subjected to lower-body surgery under caudal blockade: a randomized controlled trial.

Background: It remains unclear how much sedation is required for subumbilical surgery under caudal blockade, and sedatives may carry a poorly understood risk of late sequelae in infants. We designed a randomized controlled study to evaluate total propofol consumption and perioperative sedation quality with the avoidance of continuous perioperative sedation in infants undergoing surgery under caudal anesthesia.

Methods: Thirty-two infants (age: 0-3 months) were randomized to one of two groups in which perioperative administration of propofol was provided either "as needed" or by continuous infusion (5 mg kg h).

Efficacy of an optimal ovarian cancer screening: a best-case scenario study based on real-world data.

Purpose: To date, ovarian cancer screening in asymptomatic women has not shown a mortality benefit. The aim of this simulation study was to outline the impact of different histological subtypes on a potential stage-shift, achieved by screening.

Methods: Real-world data were derived in the period of 2000-2017 from the Klinischen Tumorregister Austria.

Impact of age on the cumulative risk of transformation in patients with chronic myelomonocytic leukaemia.

In older patients with chronic myelomonocytic leukaemia (CMML) and limited life expectancy due to age and or comorbidities, it is particularly important to consider the risk of transformation for individualised treatment decisions. There is limited information on potential differences between younger and older CMML patients regarding the cumulative risk of transformation as well as haematological, molecular and biologic characteristics. We analysed data from the Austrian Biodatabase for CMML (ABCMML) to compare these parameters in 518 CMML patients.

Using sEMG to identify seizure semiology of motor seizures.

Purpose: Accurate characterization and quantification of seizure types are critical for optimal pharmacotherapy in epilepsy patients. Technological advances have made it possible to continuously monitor physiological signals within or outside the hospital setting. This study tested the utility of single-channel surface-electromyography (sEMG) for characterization of motor epileptic seizure semiology.

CIRSE Standards of Practice on Peri-operative Anticoagulation Management During Interventional Radiology Procedures.

This CIRSE Standards of Practice document is aimed at interventional radiologists and provides best practices for peri-operative anticoagulation management during interventional radiology procedures.

The impact of visual axis position on the optical quality after implantation of multifocal intraocular lenses with different asphericity values.

Purpose: To evaluate the effect of visual axis positioning on the optical performance of the Tecnis MIOL and the Diff-aA MIOL.

Methods: In this prospective, randomized comparative study, 70 eyes of 35 subjects with senile cataract were implanted with the spherical aberration-correcting diffractive, bifocal Tecnis ZLB00 IOL and 60 eyes of 30 age-matched subjects with the spherical aberration neutral, diffractive, bifocal Diffractiva IOL. Observation procedure was performed 1, 3, and 6 months postoperatively.

The impact of hippocampal impairment on task-positive and task-negative language networks in temporal lobe epilepsy.

Objective: To study hippocampal integration within task-positive and task-negative language networks and the impact of a diseased left and right hippocampus on the language connectome in temporal lobe epilepsy (TLE).

Methods: We used functional magnetic resonance imaging (fMRI) to study a homogenous group of 32 patients with TLE (17 left) and 14 healthy controls during a verb-generation task. We performed functional connectivity analysis and quantified alterations within the language connectome and evaluated disruptions of the functional dissociation along the anterior-posterior axis of the hippocampi.

Myelomonocytic skewing in chronic myelomonocytic leukemia: phenotypic, molecular and biologic features and impact on survival.

Background: Myelomonocytic skewing is considered as a key pathophysiologic phenomenon in chronic myelomonocytic leukemia (CMML), but its prevalence and potential correlation with phenotypic, genotypic, and clinical features are poorly defined.

Methods: Skewed differentiation toward the myelomonocytic over erythroid commitment as indicated by an inverse ratio of myelomonocytic/erythroid colonies was investigated in 146 patients with CMML by semisolid in vitro cultures.

Results: There was a high prevalence of myelomonocytic skewing in patients with CMML (120/146, 82%); whereas, this phenomenon was rare in normal individuals (1/98, 1%).

The Iliofemoral tortuosity score predicts access and bleeding complications during transfemoral transcatheter aortic valve replacement: DataData from the VIenna Cardio Thoracic aOrtic valve registrY (VICTORY).

Background: Arterial tortuosity is linked to a higher risk of adverse clinical events after transfemoral transcatheter aortic valve replacement (TF-TAVR). Currently, there are no assessment tools that can quantify this variable in three-dimensional space. This study investigated the impact of novel scoring methods of iliofemoral tortuosity on access and bleeding complications after TF-TAVR.

Micro-RNA-125a mediates the effects of hypomethylating agents in chronic myelomonocytic leukemia.

Background: Chronic myelomonocytic leukemia (CMML) is an aggressive hematopoietic malignancy that arises from hematopoietic stem and progenitor cells (HSPCs). Patients with CMML are frequently treated with epigenetic therapeutic approaches, in particular the hypomethylating agents (HMAs), azacitidine (Aza) and decitabine (Dec). Although HMAs are believed to mediate their efficacy via re-expression of hypermethylated tumor suppressors, knowledge about relevant HMA targets is scarce.

Gender differences and influenza-associated mortality in hospitalized influenza A patients during the 2018/19 season.

Background: In this study we analyzed gender differences in the clinical presentation of patients with molecular confirmed influenza A. Additionally, we tried to identify predictors of influenza-associated mortality.

Materials/methods: In this prospective observational multi-center-study we included all influenza-positive patients ≥ 18 years who were hospitalized and treated on flu-isolation-wards in three hospitals in Vienna during the 2018/19 influenza season.

Fitness-Tracker Assisted Frailty-Assessment Before Transcatheter Aortic Valve Implantation: Proof-of-Concept Study.

Background: While transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of aortic valve stenosis, wearable health-monitoring devices are gradually transforming digital patient care.

Objective: The aim of this study was to develop a simple, efficient, and economical method for preprocedural frailty assessment based on parameters measured by a wearable health-monitoring device.

Methods: In this prospective study, we analyzed data of 50 consecutive patients with mean (SD) age of 77.

Placental growth factor levels neither reflect severity of portal hypertension nor portal-hypertensive gastropathy in patients with advanced chronic liver disease.

Background & Aims: Experimental data indicates that placental growth factor (PLGF) is involved in the pathophysiology of portal hypertension (PH) due to advanced chronic liver disease (ACLD). We investigated serum levels of PLGF and its "scavenger", the receptor soluble fms-like tyrosine kinase-1 (sFLT1, or sVEGFR1), in ACLD patients with different severity of PH and portal-hypertensive gastropathy (PHG).

Methods: PLGF and sVEGFR1 were measured in ACLD patients with hepatic venous pressure gradient (HVPG) ≥6 mmHg (n = 241) and endoscopic evaluation of PHG (n = 216).

Molecular Basis and Clinical Application of Growth-Factor-Independent In Vitro Myeloid Colony Formation in Chronic Myelomonocytic Leukemia.

We have originally reported that colony-forming units granulocyte/macrophage (CFU-GM) formation is an in vitro feature of chronic myelomonocytic leukemia (CMML) and a strong predictor for short survival. Elucidation of the molecular basis underlying this in vitro phenomenon could be helpful to define molecular features that predict inferior outcome in patients. We studied the correlation between the mutational landscape and spontaneous colony formation in 164 samples from 125 CMML patients.

Myelomonocytic Skewing In Vitro Discriminates Subgroups of Patients with Myelofibrosis with A Different Phenotype, A Different Mutational Profile and Different Prognosis.

Normal hematopoietic function is maintained by a well-controlled balance of myelomonocytic, megaerythroid and lymphoid progenitor cell populations which may be skewed during pathologic conditions. Using semisolid in vitro cultures supporting the growth of myelomonocytic (CFU-GM) and erythroid (BFU-E) colonies, we investigated skewed differentiation towards the myelomonocytic over erythroid commitment in 81 patients with myelofibrosis (MF). MF patients had significantly increased numbers of circulating CFU-GM and BFU-E.