Urinary Liver-Type Fatty Acid Binding Protein (L-FABP) in Early Detection and Outcome Prediction of Sepsis-Associated Acute Kidney Injury.

Introduction: Acute kidney injury (AKI) is one of the most frequent complications in septic shock cases, and has a high mortality rate. The aim of this study was to determine the value of urinary liver-type fatty acid binding protein (L-FABP) in early detection and outcome prediction of AKI in patients with sepsis and septic shock.

Methods: This prospective cohort study was conducted on patients who presented to the emergency department (ED) with sepsis or septic shock.

Usefulness of an RNA extraction-free test for the multiplexed detection of , , and Gene Fusions in Real Life FFPE Specimens of Non-Small Cell Lung Cancers.

Background: , and rearrangements occur, respectively, in 5%, 2%, and 1% non-small cell lung cancers (NSCLC). ALK and ROS1 fusion proteins detection by immunohistochemistry (IHC) has been validated for rapid patient screening, but fusions need to be confirmed by another technique and no RET IHC test is available for clinical use.

Research Design And Methods: We report herein the usefulness of the HTG EdgeSeq Assay, an RNA extraction-free test combining a quantitative nuclease protection assay with NGS, for the detection of , and fusions from 'real-life' small NSCLC samples.

30-and 90-day readmissions in lumbar spine surgery. Differences in prevalence and causes.

Background: The morbidity associated with surgical treatment of lumbar degenerative conditions has attracted increasing interest due to the economic impact on society, especially postoperative readmission. Limited studies have assessed this risk in a prospective, single-center consecutive fashion.

Objective: To assess the incidence and causes of 30- and 90-day unplanned readmission and revision surgery following surgical treatment for lumbar degenerative spine conditions at a tertiary treatment center.

Extracellular urinary microRNAs as non-invasive biomarkers of endometrial and ovarian cancer.

Introduction: Gynecological cancers account for a large number of cancer-related deaths in women. Endometrial cancer is the most prevalent, while ovarian cancer is the deadliest gynecological cancer worldwide. To overcome the clinical need for easy and rapid testing, there is a growing interest in cancer detection in non-invasive modalities.

Patient-reported outcomes from a randomized trial of neoadjuvant atezolizumab-chemotherapy in early triple-negative breast cancer.

Patient-reported outcomes data assessing patients' experience of immunotherapy treatment burden in potentially curable early-stage triple-negative breast cancer (TNBC) are lacking. These patient-reported data inform clinical benefit and decision-making for adding atezolizumab to neoadjuvant chemotherapy in early-stage TNBC. IMpassion031 (NCT03197935) randomly assigned patients with stage II/III TNBC (T2-T4d primary tumors) to 5 cycles (4 weeks/cycle) of every 2-week neoadjuvant atezolizumab 840 mg or placebo with weekly nab-paclitaxel (3 cycles) followed by every 2-week dose-dense doxorubicin+cyclophosphamide (2 cycles).

Wholistic approach: Transcriptomic analysis and beyond using archival material for molecular diagnosis.

Many neoplasms remain unclassified after histopathological examination, which requires further molecular analysis. To this regard, mesenchymal neoplasms are particularly challenging due to the combination of their rarity and the large number of subtypes, and many entities still lack robust diagnostic hallmarks. RNA transcriptomic profiles have proven to be a reliable basis for the classification of previously unclassified tumors and notably for mesenchymal neoplasms.

Standardised patient study to assess tuberculosis case detection within the private pharmacy sector in Vietnam.

Background: Of the estimated 10 million people affected by (TB) each year, one-third are never diagnosed. Delayed case detection within the private healthcare sector has been identified as a particular problem in some settings, leading to considerable morbidity, mortality and community transmission. Using unannounced standardised patient (SP) visits to the pharmacies, we aimed to evaluate the performance of private pharmacies in the detection and treatment of TB.

SRF Fusions Other Than With RELA Expand the Molecular Definition of SRF-fused Perivascular Tumors.

Pericytic tumors encompass several entities sharing morphologic and immunohistochemical features. A subset of perivascular myoid tumors associated with the SRF-RELA fusion gene was previously described. Herein, we report a series of 13 tumors belonging to this group, in which we have identified new fusion genes by RNA-sequencing, thus expanding the molecular spectrum of this entity.

Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial.

Background: Preferred neoadjuvant regimens for early-stage triple-negative breast cancer (TNBC) include anthracycline-cyclophosphamide and taxane-based chemotherapy. IMpassion031 compared efficacy and safety of atezolizumab versus placebo combined with nab-paclitaxel followed by doxorubicin plus cyclophosphamide as neoadjuvant treatment for early-stage TNBC.

Methods: This double-blind, randomised, phase 3 study enrolled patients in 75 academic and community sites in 13 countries.

Emphasizing one leg facilitates single-leg training using standard cycling equipment.

Purpose: Single-leg cycling exercise is one of the most potent, but underutilized, stimuli for promoting peripheral muscle respiratory capacity. Special ergometers used to facilitate single-leg cycling, while maintaining biomechanics similar to double-leg cycling, are not widely available. This lack of availability of specialized ergometers may explain why single-leg cycling has not been widely implemented as standard clinical practice.

Guideline-Based Clinical Assessment Versus Procalcitonin-Guided Antibiotic Use in Pneumonia: A Pragmatic Randomized Trial.

Study Objective: Efforts to reduce unnecessary and unnecessarily long antibiotic treatment for community-acquired pneumonia have been attempted through use of procalcitonin and through guidelines based on serial clinical assessment. Our aim is to compare guideline-based clinical assessment- and procalcitonin algorithm-guided antibiotic use among patients with community-acquired pneumonia.

Methods: We performed a pragmatic, randomized, multicenter trial from November 2012 to April 2015 at 12 French hospitals.

Alternative PDGFD rearrangements in dermatofibrosarcomas protuberans without PDGFB fusions.

Dermatofibrosarcoma protuberans is underlined by recurrent collagen type I alpha 1 chain-platelet-derived growth factor B chain (COL1A1-PDGFB) fusions but ~ 4% of typical dermatofibrosarcoma protuberans remain negative for this translocation in routine molecular screening. We investigated a series of 21 cases not associated with the pathognomonic COL1A1-PDGFB fusion on routine fluorescence in situ hybridization (FISH) testing. All cases displayed morphological and clinical features consistent with the diagnosis of dermatofibrosarcoma protuberans.

Smooth semi-nonparametric (SNP) estimation of the cumulative incidence function.

This paper presents a novel approach to estimation of the cumulative incidence function in the presence of competing risks. The underlying statistical model is specified via a mixture factorization of the joint distribution of the event type and the time to the event. The time to event distributions conditional on the event type are modeled using smooth semi-nonparametric densities.

Weighted analysis of composite endpoints with simultaneous inference for flexible weight constraints.

Composite endpoints are widely used as primary endpoints of randomized controlled trials across clinical disciplines. A common critique of the conventional analysis of composite endpoints is that all disease events are weighted equally, whereas their clinical relevance may differ substantially. We address this by introducing a framework for the weighted analysis of composite endpoints and interpretable test statistics, which are applicable to both binary and time-to-event data.

Rpl22 Loss Selectively Impairs αβ T Cell Development by Dysregulating Endoplasmic Reticulum Stress Signaling.

Although ribosomal proteins (RP) are thought to primarily facilitate biogenesis of the ribosome and its ability to synthesize protein, emerging evidence suggests that individual RP can perform critical regulatory functions that control developmental processes. We showed previously that despite the ubiquitous expression of the RP ribosomal protein L22 (Rpl22), germline ablation of Rpl22 in mice causes a selective, p53-dependent block in the development of αβ, but not γδ, T cell progenitors. Nevertheless, the basis by which Rpl22 loss selectively induces p53 in αβ T cell progenitors remained unclear.

A novel regulation of PD-1 ligands on mesenchymal stromal cells through MMP-mediated proteolytic cleavage.

Whether fibroblasts regulate immune response is a crucial issue in the modulation of inflammatory responses. Herein, we demonstrate that foreskin fibroblasts (FFs) potently inhibit CD3 T cell proliferation through a mechanism involving early apoptosis of activated T cells. Using blocking antibodies, we demonstrate that the inhibition of T cell proliferation occurs through cell-to-cell interactions implicating PD-1 receptor expressed on T cells and its ligands, PD-L1 and PD-L2, on fibroblasts.

Regulatory Roles of Rpl22 in Hematopoiesis: An Old Dog with New Tricks.

Ribosomal proteins have long been known to serve critical roles in facilitating the biogenesis of the ribosome and its ability to synthesize proteins. However, evidence is emerging that suggests ribosomal proteins are also capable of performing tissue-restricted, regulatory functions that impact normal development and pathological conditions, including cancer. The challenge in studying such regulatory functions is that elimination of many ribosomal proteins also disrupts ribosome biogenesis and/or function.

Clinical implications of reduced susceptibility to fluoroquinolones in paediatric Shigella sonnei and Shigella flexneri infections.

Objectives: We aimed to quantify the impact of fluoroquinolone resistance on the clinical outcome of paediatric shigellosis patients treated with fluoroquinolones in southern Vietnam. Such information is important to inform therapeutic management for infections caused by this increasingly drug-resistant pathogen, responsible for high morbidity and mortality in young children globally.

Methods: Clinical information and bacterial isolates were derived from a randomized controlled trial comparing gatifloxacin with ciprofloxacin for the treatment of paediatric shigellosis.

Prediction of desmoid tumor progression using miRNA expression profiling.

Desmoid tumor is a rare connective tissue tumor with locoregional aggressiveness but unpredictable behavior. The miRNA profile was ascertained for 26 patients included in the Desminib phase II trial and an independent validation cohort of 15 patients. Predictive and prognostic supervised analysis on the Desminib cohort failed to identify miRNAs differentially expressed between progressive and non-progressive patients under imatinib treatment or between progressive and non-progressive patients after discontinuation of imatinib.

The ribosomal protein Rpl22 controls ribosome composition by directly repressing expression of its own paralog, Rpl22l1.

Most yeast ribosomal protein genes are duplicated and their characterization has led to hypotheses regarding the existence of specialized ribosomes with different subunit composition or specifically-tailored functions. In yeast, ribosomal protein genes are generally duplicated and evidence has emerged that paralogs might have specific roles. Unlike yeast, most mammalian ribosomal proteins are thought to be encoded by a single gene copy, raising the possibility that heterogenous populations of ribosomes are unique to yeast.

Insulin-like growth factor type 1 receptor (IGF-1R) exclusive nuclear staining: a predictive biomarker for IGF-1R monoclonal antibody (Ab) therapy in sarcomas.

Aims: A minority of patients with advanced sarcoma achieve prolonged progression free survival (PFS) with insulin growth factor type 1 receptor (IGF-1R) monoclonal antibody (Ab) therapy. A biomarker identifying those patients beforehand would be useful to select patients for the development of these agents.

Methods: This single centre series includes patients with unresectable or metastatic soft tissue sarcomas (STS), Ewing sarcoma (ES) and osteosarcoma treated with IGF-1R Ab (R1507, IMC-A12, SCH 717454 and CP-751.