Anti-CD74 IgA autoantibodies in radiographic axial spondyloarthritis: a longitudinal Swedish study.

Objectives: Antibodies against anti-CD74 are related to axial spondyloarthritis (axSpA). The objectives were (i) to study IgA anti-CD74 in radiographic (r)-axSpA patients in the Backbone cohort and to calculate the sensitivity and specificity of anti-CD74, (ii) to study the fluctuation of IgA anti-CD74 levels in prospectively collected samples, and (iii) to explore the relation between IgA anti-CD74 and radiographic spinal changes.

Methods: IgA anti-CD74 was analysed by ELISA in 155 patients with r-axSpA and age- and sex-matched controls.

Evaluation of an Adaptive Dynamic Compensation System in Cochlear Implant Listeners.

Cochlear implant (CI) sound processing typically uses a front-end automatic gain control (AGC), reducing the acoustic dynamic range (DR) to control the output level and protect the signal processing against large amplitude changes. It can also introduce distortions into the signal and does not allow a direct mapping between acoustic input and electric output. For speech in noise, a reduction in DR can result in lower speech intelligibility due to compressed modulations of speech.

Completion of radical hysterectomy does not improve survival of patients with cervical cancer and intraoperatively detected lymph node involvement: ABRAX international retrospective cohort study.

Background: The management of cervical cancer patients with intraoperative detection of lymph node involvement remains controversial. Since all these patients are referred for (chemo)radiation after the surgery, the key decision is whether radical hysterectomy should be completed as originally planned, taking into account an additional morbidity associated with extensive surgical dissection prior to adjuvant treatment. The ABRAX study investigated whether completing a radical uterine procedure is associated with an improved oncological outcome of such patients.

The Distribution of Alpha-1 Antitrypsin Genotypes Between Patients with COPD/Emphysema, Asthma and Bronchiectasis.

Purpose: Alpha-1-antitrypsin deficiency (AATD) is a rare hereditary condition characterized by low circulating levels of alpha-1antitrypsin (AAT). While the association between AATD and COPD/emphysema is undisputed, the association between AATD and asthma or bronchiectasis is still a matter of debate.

Aims And Objectives: Our study aimed to investigate the distribution of AAT genotypes between patients with COPD/emphysema, asthma and bronchiectasis.

Synthetic rewiring and boosting type I interferon responses for visualization and counteracting viral infections.

Mammalian first line of defense against viruses is accomplished by the interferon (IFN) system. Viruses have evolved numerous mechanisms to reduce the IFN action allowing them to invade the host and/or to establish latency. We generated an IFN responsive intracellular hub by integrating the synthetic transactivator tTA into the chromosomal Mx2 locus for IFN-based activation of tTA dependent expression modules.

Perception and prediction of loudness in sound coding strategies using simultaneous electric stimulation.

Cochlear Implant (CI) sound coding strategies based on simultaneous stimulation lead to an increased loudness percept when compared to sequential stimulation using the same current levels. This is due to loudness summation as a result of channel interactions. Studying the loudness perception evoked by dual-channels compared to single-channels can be useful to optimize sound coding strategies that use simultaneous current pulses.

Cochlear implantation in an animal model documents cochlear damage at the tip of the implant.

Introduction: Electrocochleography has recently emerged as a diagnostic tool in cochlear implant surgery, purposing hearing preservation and optimal electrode positioning.

Objective: In this experimental study, extra-cochlear potentials were obtained during cochlear implant surgery in guinea pigs. The aim was to determine electrophysiological changes indicating cochlear trauma after cochleostomy and after electrode implantation in different insertion depths.

Concordance between CA-125 and RECIST progression in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer treated in the SOLO2 trial with olaparib as maintenance therapy after response to chemotherapy.

Background: Limited evidence exists to support CA-125 as a valid surrogate biomarker for progression in patients with ovarian cancer on maintenance PARP inhibitor (PARPi) therapy. We aimed to assess the concordance between CA-125 and Response Evaluation Criteria in Solid Tumours (RECIST) criteria for progression in patients with BRCA mutations on maintenance PARPi or placebo.

Methods: We extracted data on progression as defined by Gynecologic Cancer InterGroup CA-125, investigator- and independent central-assessed RECIST from the SOLO2/ENGOT-ov21(NCT01874353) trial.

Effect of Spectral Contrast Enhancement on Speech-on-Speech Intelligibility and Voice Cue Sensitivity in Cochlear Implant Users.

Objectives: Speech intelligibility in the presence of a competing talker (speech-on-speech; SoS) presents more difficulties for cochlear implant (CI) users compared with normal-hearing listeners. A recent study implied that these difficulties may be related to CI users' low sensitivity to two fundamental voice cues, namely, the fundamental frequency (F0) and the vocal tract length (VTL) of the speaker. Because of the limited spectral resolution in the implant, important spectral cues carrying F0 and VTL information are expected to be distorted.

The effect of synchronized linked band selection on speech intelligibility of bilateral cochlear implant users.

Normal-hearing (NH) listeners have the ability to combine the audio input perceived by each ear to extract target information in challenging listening scenarios. Bilateral cochlear implant (BiCI) users, however, do not benefit as much as NH listeners do from a bilateral input. In this study, we investigate the effect that bilaterally synchronized electrical stimulation, bilaterally linked band selection, and ideal binary masks (IdBMs) have on the ability of 10 BiCIs to understand speech in background noise.

Increasing methylation of sperm rDNA and other repetitive elements in the aging male mammalian germline.

In somatic cells/tissues, methylation of ribosomal DNA (rDNA) increases with age and age-related pathologies, which has a direct impact on the regulation of nucleolar activity and cellular metabolism. Here, we used bisulfite pyrosequencing and show that methylation of the rDNA transcription unit including upstream control element (UCE), core promoter, 18S rDNA, and 28S rDNA in human sperm also significantly increases with donor's age. This positive correlation between sperm rDNA methylation and biological age is evolutionarily conserved among mammals with widely different life spans such as humans, marmoset, bovine, and mouse.

Controlled Functional Zonation of Hepatocytes by Engineering of Wnt Signaling.

Key liver functions, including protein synthesis, carbohydrate metabolism, and detoxification, are performed by specific populations of hepatocytes that are defined by their relative positions within the liver lobules. On a molecular level, the functional heterogeneity with periportal and pericentral phenotypes, so-called metabolic liver zonation, is mainly established by a gradient of canonical Wnt signaling activity. Since the relevant physiological cues are missing in liver models, they fail to reflect the functional heterogeneity and thus lack many liver functions.

Design and Evaluation of a Real-Time Audio Source Separation Algorithm to Remix Music for Cochlear Implant Users.

A cochlear implant (CI) is a surgically implanted electronic device that partially restores hearing to people suffering from profound hearing loss. Although CI users, in general, obtain a very good reception of continuous speech in the absence of background noise, they face severe limitations in the context of music perception and appreciation. The main reasons for these limitations are related to channel interactions created by the broad spread of electrical fields in the cochlea and to the low number of electrodes that stimulate it.

Liver Phenotypes of European Adults Heterozygous or Homozygous for Pi∗Z Variant of AAT (Pi∗MZ vs Pi∗ZZ genotype) and Noncarriers.

Background & Aims: Homozygosity for the Pi∗Z variant of the gene that encodes the alpha-1 antitrypsin peptide (AAT), called the Pi∗ZZ genotype, causes a liver and lung disease called alpha-1 antitrypsin deficiency. Heterozygosity (the Pi∗MZ genotype) is a risk factor for cirrhosis in individuals with liver disease. Up to 4% of Europeans have the Pi∗MZ genotype; we compared features of adults with and without Pi∗MZ genotype among persons without preexisting liver disease.

Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial.

Background: State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin-paclitaxel or carboplatin-gemcitabine) or the most active non-bevacizumab regimen: carboplatin-pegylated liposomal doxorubicin. The aim of this head-to-head trial was to compare a standard bevacizumab-containing regimen versus carboplatin-pegylated liposomal doxorubicin combined with bevacizumab.

Methods: This multicentre, open-label, randomised, phase 3 trial, was done in 159 academic centres in Germany, France, Australia, Austria, and the UK.

IgA antibodies against CD74 are associated with structural damage in the axial skeleton in patients with axial spondyloarthritis.

Objectives: To study the association between the presence of antibodies against CD74 and structural damage in the sacroiliac joints and spine in patients with axial spondyloarthritis (axSpA).

Methods: Antibodies against CD74 were measured in the sera of patients with axSpA from 2 cohorts: 1. An observational cohort from Damp in Northern Germany and 2.

Impaired proteolysis by SPPL2a causes CD74 fragment accumulation that can be recognized by anti-CD74 autoantibodies in human ankylosing spondylitis.

Ankylosing spondylitis (AS) is associated with autoantibody production to class II MHC-associated invariant chain peptide, CD74/CLIP. In this study, we considered that anti-CD74/CLIP autoantibodies present in sera from AS might recognize CD74 degradation products that accumulate upon deficiency of the enzyme signal peptide peptidase-like 2A (SPPL2a). We analyzed monocytes from healthy controls (n = 42), psoriatic arthritis (n = 25), rheumatoid arthritis (n = 16), and AS patients (n = 15) for SPPL2a enzyme activity and complemented the experiments using SPPL2a-sufficient and -deficient THP-1 cells.

Protocol for the EARCO Registry: a pan-European observational study in patients with α-antitrypsin deficiency.

Rationale And Objectives: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that leads to an increased risk of emphysema and liver disease. Despite extensive investigation, there remain unanswered questions concerning the natural history, pathophysiology, genetics and the prognosis of the lung disease in association with AATD. The European Alpha-1 Clinical Research Collaboration (EARCO) is designed to bring together researchers from European countries and to create a standardised database for the follow-up of patients with AATD.

Fracture Ultrasound of the Extremities.

Fracture ultrasound has increasingly come into the focus of international research. A growing number of original articles and a meta-analysis show that wrist fractures can be diagnosed without X-ray in children up to 12 years. Further original publications state that elbow fractures can be ruled out by exclusion of intraarticular effusion and in proximal humerus fractures the number of X-rays is reduced by about 50 %, while the quality of diagnosis is improved.

Outcome of children relapsing after first allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: a retrospective I-BFM analysis of 333 children.

Outcome of 333 children with acute myeloid leukaemia relapsing after a first allogeneic haematopoietic stem cell transplantation was analyzed. Four-year probability of overall survival (4y-pOS) was 14%. 4y-pOS for 122 children receiving a second haematopoietic stem cell transplantation was 31% and 3% for those that did not (P = <0·0001).

Autoantibodies against P29ING4 are associated with complex regional pain syndrome.

Introduction: Complex regional pain syndrome (CRPS) is a complication following trauma or surgery and may be difficult to diagnose since biomarkers are lacking. Using protein array technology, we found antibodies binding to p29ING4, which we further characterized using ELISA.

Methods: Thirty-six sera of early-stage type 1 CRPS, 66 sera of rheumatoid arthritis (RA), 53 sera of axial spondyloarthritis (axSpA), 29 sera of psoriatic arthritis (PsA), 22 sera of patients after radial fractures (trauma control), and 100 sera of blood donors (BD) were analyzed for anti-p29ING4.

Cost-effectiveness analysis comparing ceftazidime/avibactam (CAZ-AVI) as empirical treatment comparing to ceftolozane/tazobactam and to meropenem for complicated intra-abdominal infection (cIAI).

Background: The rising incidence of resistance to currently available antibiotics among pathogens, particularly Gram-negative pathogens, in complicated intra-abdominal infections (cIAIs) has become a challenge for clinicians. Ceftazidime/avibactam (CAZ-AVI) is a fixed-dose antibiotic approved in Europe and the United States for treating (in combination with metronidazole) cIAI in adult hospitalised patients who have limited or no alternative treatment options. The approval was based on the results of RECLAIM, a Phase III, parallel-group, comparative study (RECLAIM 1 [NCT01499290] and RECLAIM 2 [NCT01500239]).

Influence of single-sided deafness on the auditory capacity of the better ear.

Background: Patients with single-sided deafness (SSD) are limited by their asymmetric hearing in various areas of everyday life.

Objective: The aim of this investigation was to perform an age-correlated comparison of the hearing threshold of the better ear of SSD patients with a normal-hearing (NH) reference cohort. In addition, the potential influence of etiology, duration of deafness, and cochlear implantation (CI) of the poorer ear on the peripheral hearing ability of the better ear was investigated.

Post-operative abdominal infections: epidemiology, operational definitions, and outcomes.

Postoperative abdominal infections are an important and heterogeneous health challenge in intensive care units (ICU) and encompass postoperative infectious processes developing within the abdominal cavity that may be caused by either bacterial or fungal pathogens. In this narrative review, we discuss postoperative bacterial and fungal abdominal infections, covering also multidrug-resistant (MDR) pathogens. We also cover clinically preeminent aspects such as the definition of postoperative abdominal infections, which still remains difficult owing to their heterogeneity in patient characteristics, clinical presentation, ecology and antimicrobial treatment.

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: "AbSeS", a multinational observational cohort study and ESICM Trials Group Project.

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock).

Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis.