Benefits and Safety of Empiric Antibiotic Treatment Active Against KPC-Producing for Febrile Neutropenic Episodes in Colonized Children with Acute Leukemia-An 8-Year Retrospective Observational Study.

In children with acute leukemia (AL), the mortality rate from carbapenemase (KPC)-producing bloodstream infection (KPC-KpBSI) exceeds 50%, highest when active treatment is delayed. Neutropenic KPC- carriers are at high risk of KPC-KpBSI, and preemptive empiric antibiotic treatment (EAT) of febrile neutropenic episodes (FNEs) active against KPC- may reduce this mortality. We conducted an 8-year (2014-2021) retrospective observational study of 112 febrile neutropenic episodes (FNEs) in 32 children with AL who were KPC- carriers: standard EAT for 39 FNEs and active EAT for 73 FNEs (52 ceftazidime/avibactam (CAZAVI)-based and 21 colistin-based combinations, and 5 CAZAVI monotherapy).

Validation of claims-based algorithms for rheumatoid arthritis in Japan: Results from the VALIDATE-J study.

Aim: Validity of Algorithms in Large Databases: Infectious Diseases, Rheumatoid Arthritis, and Tumor Evaluation in Japan (VALIDATE-J) study examined algorithms for identifying rheumatoid arthritis (RA) in Japanese claims data.

Methods: VALIDATE-J was a multicenter, cross-sectional retrospective study. Disease-identifying algorithms were used to detect RA diagnosed between January 2012 and December 2016 using claims data from two Japanese hospitals.

Short-course combination treatment for experimental chronic Chagas disease.

Chagas disease, caused by the protozoan parasite , affects millions of people in the Americas and across the world, leading to considerable morbidity and mortality. Current treatment options, benznidazole (BNZ) and nifurtimox, offer limited efficacy and often lead to adverse side effects because of long treatment durations. Better treatment options are therefore urgently required.

Validity of claims-based diagnoses for infectious diseases common among immunocompromised patients in Japan.

Background: To validate Japanese claims-based disease-identifying algorithms for herpes zoster (HZ), Mycobacterium tuberculosis (MTB), nontuberculous mycobacteria infections (NTM), and Pneumocystis jirovecii pneumonia (PJP).

Methods: VALIDATE-J, a multicenter, cross-sectional, retrospective study, reviewed the administrative claims data and medical records from two Japanese hospitals. Claims-based algorithms were developed by experts to identify HZ, MTB, NTM, and PJP cases among patients treated 2012-2016.

Liquid Biopsy Detecting Circulating Tumor Cells in Patients with Non-Small Cell Lung Cancer: Preliminary Results of a Pilot Study.

Lung cancer is still the leading cause of cancer-related death worldwide. Interest is growing towards early detection and advances in liquid biopsy to isolate circulating tumor cells (CTCs). This pilot study aimed to detect epithelial CTCs in the peripheral blood of early-stage non-small cell lung cancer (NSCLC) patients.

Discovery of Potent Cholinesterase Inhibition-Based Multi-Target-Directed Lead Compounds for Synaptoprotection in Alzheimer's Disease.

Drug development efforts that focused on single targets failed to provide effective treatment for Alzheimer's disease (AD). Therefore, we designed cholinesterase inhibition (ChEI)-based multi-target-directed ligands (MTDLs) to simultaneously target AD-related receptors. We built a library of 70 compounds, sequentially screened for ChEI, and determined σR, σR, NMDAR-GluN2B binding affinities, and P2X7R antagonistic activities.

Utility of procalcitonin and C-reactive protein as predictors of Gram-negative bacteremia in febrile hematological outpatients.

This study was designed to determine the utility of procalcitonin (PCT) and C-reactive protein (CRP) as predictors of Gram-negative bloodstream infection (GN-BSI) in hematological febrile outpatients at the time of the emergency unit admission. Overall, 286 febrile episodes, which included 42 GN-BSI (16%), were considered. PCT levels at patient admission were statistically higher in GNB-BSI when compared to Gram-positive bacteria BSI (median 4.

Exploring aromatic cage flexibility of the histone methyllysine reader protein Spindlin1 and its impact on binding mode prediction: an in silico study.

Some of the main challenges faced in drug discovery are pocket flexibility and binding mode prediction. In this work, we explored the aromatic cage flexibility of the histone methyllysine reader protein Spindlin1 and its impact on binding mode prediction by means of in silico approaches. We first investigated the Spindlin1 aromatic cage plasticity by analyzing the available crystal structures and through molecular dynamic simulations.

Structure-Based Design, Docking and Binding Free Energy Calculations of A366 Derivatives as Spindlin1 Inhibitors.

The chromatin reader protein Spindlin1 plays an important role in epigenetic regulation, through which it has been linked to several types of malignant tumors. In the current work, we report on the development of novel analogs of the previously published lead inhibitor . In an effort to improve the activity and explore the structure-activity relationship (SAR), a series of 21 derivatives was synthesized, tested in vitro, and investigated by means of molecular modeling tools.

Validity of claims-based algorithms for selected cancers in Japan: Results from the VALIDATE-J study.

Purpose: Real-world data from large administrative claims databases in Japan have recently become available, but limited evidence exists to support their validity. VALIDATE-J validated claims-based algorithms for selected cancers in Japan.

Methods: VALIDATE-J was a multicenter, cross-sectional, retrospective study.

Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver.

Metastasis is facilitated by the formation of a "premetastatic niche," which is fostered by primary tumor-derived factors. Colorectal cancer (CRC) metastasizes mainly to the liver. We show that the premetastatic niche in the liver is induced by bacteria dissemination from primary CRC.

Design, synthesis, and biological evaluation of new urolithin amides as multitarget agents against Alzheimer's disease.

A series of urolithin amide (i.e., URO-4-URO-10 and THU-4-THU-10) derivatives was designed and synthesized, and their chemical structures were confirmed with spectroscopic techniques and elemental analysis.

Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study.

Background: There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer.

Methods: We conducted a cohort study of breast cancer patients initiating palbociclib and fulvestrant from February 2015 to September 2017 using the HealthCore Integrated Research Database (HIRD), a longitudinal claims database of commercial health plan members in the United States. The historical comparator cohort comprised patients initiating fulvestrant monotherapy from January 2011 to January 2015.

Focused Shockwave Treatment for Greater Trochanteric Pain Syndrome: A Multicenter, Randomized, Controlled Clinical Trial.

Background: Greater trochanteric pain syndrome (GTPS) is a condition of lateral hip pain. Its physiopathology remains unknown, and there is no consensus on optimal management. The aim of this study was to assess the effectiveness of electromagnetic-focused extracorporeal shockwave treatment (F-ESWT) in patients with GTPS.

Synthesis, Characterization, Molecular Docking, and Biological Activities of Some Natural and Synthetic Urolithin Analogs.

Urolithins (that is, hydroxy substituted benzo[c]chromen-6-one derivatives) are formed within the gastrointestinal tract following to the exposure to various ellagitannin rich diet, particularly involving pomegranate, nuts, and berries. Regarding the bioavailability deficiency of ellagitannins, the biological activities obtained through the extracts of these dietaries are attributed to the urolithin compounds, since they are bioavailable. Particularly, there are studies indicating the importance of ellagitannin-rich food for protective and alternative treatment of Alzheimer's Disease (AD).

Isavuconazole Therapy of Disseminated and Encephalic Infection in an Acute Myeloid Leukemia Patient Treated with Midostaurin.

Background: is a rare and emerging opportunistic fungus, involving immunocompromised hosts, in particular, neutropenic patients after chemotherapy. We report a case of disseminated and cerebral infection by , in a 68-year-old woman affected by acute myeloid leukemia that was successfully managed with liposomal amphotericin B and isavuconazole.

Conclusions: This case illustrates the feasibility of isavuconazole therapy in the treatment of a infection when co-administered with midostaurin.

Management of Muscle Spasticity in Children with Cerebral Palsy by Means of Extracorporeal Shockwave Therapy: A Systematic Review of the Literature.

The purpose of this systematic review was to investigate the effectiveness of extracorporeal shockwave therapy for the management of muscle spasticity in children with cerebral palsy. An electronic database search was performed to identify studies relevant to the research question. Assessment of the quality of evidence in all relevant studies was performed with the help of the Oxford Center for Evidence-based Medicine guide.

MMP-14 degrades tropoelastin and elastin.

Matrix metalloproteinases are a class of enzymes, which degrade extracellular matrix components such as collagens, elastin, laminin or fibronectin. So far, four matrix metalloproteinases have been shown to degrade elastin and its precursor tropoelastin, namely matrix metalloproteinase-2, -7, -9 and -12. This study focuses on investigating the elastinolytic capability of membrane-type 1 matrix metalloproteinase, also known as matrix metalloproteinase-14.