e-ISSN: Pending

Browse the failure-mode index

12,222 real negative results, null findings, and replication failures in Medicine. Search the index →

WASTE indexes published research — it does not host or republish full papers. Each entry is a metadata record compiled from open scholarly databases; the abstract is shown in full only where the paper is openly licensed, otherwise a short excerpt under fair use. Classifications are automated and approximate.

Replication FailureOpen accessMedicine

Predisposition to Childhood Otitis Media and Genetic Polymorphisms within the Toll-Like Receptor 4 (TLR4) Locus

Lena Hafrén, Elísabet Einarsdóttir, Erna Kentala et al. · 2015 · PLoS ONE

BACKGROUND: Predisposition to childhood otitis media (OM) has a strong genetic component, with polymorphisms in innate immunity genes suspected to contribute to risk. Studies on several genes have been conducted, but most associations have failed to replicate in independent cohorts. METHODS: We investigated 53 gene polymorphisms in a Finnish cohort of 624 cases and 778 controls. A positive association signal was followed up in a tagging approach and tested in an independent Finnish cohort of 205 cases, in a British cohort of 1269 trios, as well as in two cohorts from the United States (US); on

View details →
Negative / Null Result ReportOpen accessMedicine

INHALE WP3, a multicentre, open-label, pragmatic randomised controlled trial assessing the impact of rapid, ICU-based, syndromic PCR, versus standard-of-care on antibiotic stewardship and clinical outcomes in hospital-acquired and ventilator-associated pneumonia

Virve I. Enne, Susan Stirling, Julie Barber et al. · 2025 · Intensive Care Medicine

PURPOSE: INHALE investigated the impact of seeking pathogens by PCR on antibiotic stewardship and clinical outcomes in hospital-acquired and ventilator-associated pneumonia (HAP and VAP). METHODS: This pragmatic multicentre, open-label RCT…

View details →
Negative / Null Result ReportOpen accessMedicine

Comparison of placebo and best available therapy for the treatment of myelofibrosis in the phase 3 COMFORT studies

Ruben A. Mesa, Jean‐Jacques Kiladjian, Srđan Verstovšek et al. · 2013 · Haematologica

Prior to Janus kinase inhibitors, available therapies for myelofibrosis were generally supportive and did not improve survival. This analysis compares efficacy outcomes of patients with myelofibrosis in the control arms (placebo [n=154]…

View details →
Negative / Null Result ReportOpen accessMedicine

Reducing mortality with cotrimoxazole preventive therapy at initiation of antiretroviral therapy in South Africa

Christopher J. Hoffmann, Katherine Fielding, Salome Charalambous et al. · 2010 · AIDS

OBJECTIVE: To assess the effectiveness of cotrimoxazole preventive therapy (CPT) among individuals with CD4 cell count above 200 cells/microl and varying WHO clinical stages in reducing mortality during combination antiretroviral therapy…

View details →
Negative / Null Result ReportOpen accessMedicine

Significant associations of age, menopausal status and lifestyle factors with visceral adiposity in African-American and European-American women

Ellen W. Demerath, Nikki Lynn Rogers, Derek Reed et al. · 2010 · Annals of Human Biology

BACKGROUND: Elevated visceral adiposity is strongly predictive of cardiometabolic disease, but, due to the high cost of biomedical imaging, assessment of factors contributing to normal variation in visceral (VAT) and subcutaneous (SAT)…

View details →
Replication FailureMedicine

Abstract S4-2: First Efficacy Results of a Randomized, Open-Label, Phase III Study of Adjuvant Doxorubicin Plus Cyclophosphamide, Followed by Docetaxel with or without Capecitabine, in High-Risk Early Breast Cancer

Joyce O’Shaughnessy, D Paul, Christopher Stokoe et al. · 2010 · Cancer Research

Abstract Background: Combination regimens incorporating anthracyclines and taxanes are among the most effective for EBC and are particularly suitable for pts with high-risk disease. Significant efficacy benefit has been shown in phase III…

View details →
Negative / Null Result ReportOpen accessMedicine

Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial

Cissy Kityo, Alexander J. Szubert, Abraham Siika et al. · 2018 · PLoS Medicine

BACKGROUND: In sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integrase inhibitors lead to significantly more rapid declines in HIV viral load (VL) than all other ART classes. We hypothesised that intensifying standard triple-drug ART with the integrase inhibitor, raltegravir, would reduce HIV VL fast

View details →
Negative / Null Result ReportOpen accessMedicine

Effect on Virulence and Pathogenicity of H5N1 Influenza A Virus through Truncations of NS1 eIF4GI Binding Domain

Hongbo Zhou, Jiping Zhu, Jiagang Tu et al. · 2010 · The Journal of Infectious Diseases

To study the effect of NS1 eIF4GI binding domain on virulence and pathogenicity of H5N1 influenza A virus, 5 recombinant H5N1 viruses encoding eIF4GI binding domain-truncated NS1 proteins and parental NS1 (NS1‐wt) were generated by an…

View details →
Negative / Null Result ReportMedicine

Characterization of H5N2 influenza viruses isolated in South Korea and their influence on the emergence of a novel H9N2 influenza virus

Hye-Ryoung Kim, Choi-Ku Park, Jae‐Ku Oem et al. · 2010 · Journal of General Virology

We characterized low pathogenic avian influenza (LPAI) H5N2 and H9N2 viruses isolated in South Korea from 2008 to 2009. Genetic analysis of the H5N2 viruses isolated from wild birds and domestic ducks demonstrated that they were related to…

View details →
Negative / Null Result ReportOpen accessMedicine

Primary mucosal melanoma of the head and neck in Denmark, 1982–2012: Demographic and clinical aspects. A retrospective DAHANCA study

Mads Lawaetz, Fatima Birch‐Johansen, Søren Friis et al. · 2016 · Acta Oncologica

Background The study was performed to determine the epidemiological, clinical, and histopathological characteristics and prognosis of primary mucosal melanoma of the head and neck (MMHN) in Denmark. Material and methods This was a national…

View details →
Negative / Null Result ReportOpen accessMedicine

Novel agents and strategies for overcoming EGFR TKIs resistance

Feiyu Niu, Yi‐Long Wu · 2014 · Experimental Hematology and Oncology

Since the recognition of epidermal growth factor receptor (EGFR) as a therapeutic target, EGFR tyrosine kinase inhibitors (TKIs) have been used in lung cancer patients with EGFR mutations, which has been a major breakthrough for lung cancer treatment.. The progression-free survival (PFS) of patients with EGFR mutations treated with EGFR TKIs is significantly prolonged compared with that of patients who underwent standard chemotherapy. However, all patients who initially respond to EGFR TKIs eventually develop acquired resistance (AR). Many small molecule agents and monoclonal antibodies (McAb)

View details →
Negative / Null Result ReportOpen accessMedicine

The quinoline bromoquinol exhibits broad-spectrum antifungal activity and induces oxidative stress and apoptosis in Aspergillus fumigatus

Dafna Ben Yaakov, Yana Shadkchan, Nathaniel D. Albert et al. · 2017 · Journal of Antimicrobial Chemotherapy

Objectives: Over the last 30 years, the number of invasive fungal infections among immunosuppressed patients has increased significantly, while the number of effective systemic antifungal drugs remains low. The aim of this study was to…

View details →
Negative / Null Result ReportOpen accessMedicine

A mouse model of hepatic encephalopathy: bile duct ligation induces brain ammonia overload, glial cell activation and neuroinflammation

Wouter Claeys, Lien Van Hoecke, Anja Geerts et al. · 2022 · Scientific Reports

Hepatic encephalopathy (HE) is a common complication of chronic liver disease, characterized by an altered mental state and hyperammonemia. Insight into the brain pathophysiology of HE is limited due to a paucity of well-characterized HE models beyond the rat bile duct ligation (BDL) model. Here, we assess the presence of HE characteristics in the mouse BDL model. We show that BDL in C57Bl/6j mice induces motor dysfunction, progressive liver fibrosis, liver function failure and hyperammonemia, all hallmarks of HE. Swiss mice however fail to replicate the same phenotype, underscoring the import

View details →
Negative / Null Result ReportOpen accessMedicine

Significant association between clinical characteristics and changes in peripheral immuno-phenotype in large vessel vasculitis

Kotaro Matsumoto, Katsuya Suzuki, Keiko Yoshimoto et al. · 2019 · Arthritis Research & Therapy

Abstract Background Large vessel vasculitis (LVV) is a type of vasculitis characterized by granulomatous inflammation of medium- and large-sized arteries. Clinical assessment of acute phase reactants has been conventionally used to diagnose and monitor diseases; however, accurate assessment of vascular disease activity status can be difficult. In this study, we investigated comprehensive immuno-phenotyping to explore useful biomarkers associated with clinical characteristics. Methods Consecutive patients with newly diagnosed LVV who visited our institution between May 2016 and May 2019 were en

View details →
Negative / Null Result ReportOpen accessMedicine

BAFF-neutralizing interaction of belimumab related to its therapeutic efficacy for treating systemic lupus erythematosus

Woo‐Ri Shin, Hyun Tae Lee, Heejin Lim et al. · 2018 · Nature Communications

BAFF, a member of the TNF superfamily, has been recognized as a good target for autoimmune diseases. Belimumab, an anti-BAFF monoclonal antibody, was approved by the FDA for use in treating systemic lupus erythematosus. However, the molecular basis of BAFF neutralization by belimumab remains unclear. Here our crystal structure of the BAFF-belimumab Fab complex shows the precise epitope and the BAFF-neutralizing mechanism of belimumab, and demonstrates that the therapeutic activity of belimumab involves not only antagonizing the BAFF-receptor interaction, but also disrupting the formation of th

View details →
Negative / Null Result ReportOpen accessMedicine

Interrogating the immune-modulating roles of radiation therapy for a rational combination with immune-checkpoint inhibitors in treating pancreatic cancer

Kenji Fujiwara, May Tun Saung, Hao Jing et al. · 2020 · Journal for ImmunoTherapy of Cancer

Background Radiation therapy (RT) has the potential to enhance the efficacy of immunotherapy, such as checkpoint inhibitors, which has dramatically altered the landscape of treatments for many cancers, but not yet for pancreatic ductal…

View details →
Replication FailureOpen accessMedicine

High-Dose Versus Standard-Dose Intensity-Modulated Radiotherapy With Concurrent Paclitaxel Plus Carboplatin for Patients With Thoracic Esophageal Squamous Cell Carcinoma: A Randomized, Multicenter, Open-Label, Phase 3 Superiority Trial

Jing You, Shuchai Zhu, Jiancheng Li et al. · 2022 · International Journal of Radiation Oncology*Biology*Physics

PurposeThe standard dose (SD) of definitive concurrent chemoradiotherapy (dCRT) remains 50.4 Gy in patients with esophageal cancer; a higher dose, when applied with conventional radiation therapy techniques, increases toxicities without…

View details →
Negative / Null Result ReportOpen accessMedicine

Randomized Controlled Trial of Ultrasound-guided Fluid Resuscitation of Sepsis-Induced Hypoperfusion and Septic Shock

Khrongwong Musikatavorn, Poj Plitawanon, Suthaporn Lumlertgul et al. · 2021 · Western Journal of Emergency Medicine

INTRODUCTION: The ultrasound measurement of inferior vena cava (IVC) diameter change during respiratory phase to guide fluid resuscitation in shock patients is widely performed, but the benefit on reducing the mortality of sepsis patients is questionable. The study objective was to evaluate the 30-day mortality rate of patients with sepsis-induced tissue hypoperfusion (SITH) and septic shock (SS) treated with ultrasound-guided fluid management (UGFM) using ultrasonographic change of the IVC diameter during respiration compared with those treated with the usual-care strategy. METHODS: This was

View details →
Negative / Null Result ReportOpen accessMedicine

Intratumoral administration of CD1c (BDCA-1)+ and CD141 (BDCA-3)+ myeloid dendritic cells in combination with talimogene laherparepvec in immune checkpoint blockade refractory advanced melanoma patients: a phase I clinical trial

Julia Katharina Schwarze, Jens Tijtgat, Gil Awada et al. · 2022 · Journal for ImmunoTherapy of Cancer

Background Intratumoral (IT) myeloid dendritic cells (myDCs) play a pivotal role in initiating antitumor immune responses and relicensing of anti-tumor cytotoxic T lymphocytes within the tumor microenvironment. Talimogene laherparepvec…

View details →
Negative / Null Result ReportOpen accessMedicine

Identification of Susceptibility Genes for Peritoneal, Ovarian, and Deep Infiltrating Endometriosis Using a Pooled Sample-Based Genome-Wide Association Study

Bruno Borghese, Jörg Tost, Magalie de Surville et al. · 2015 · BioMed Research International

Characterizing genetic contributions to endometriosis might help to shorten the time to diagnosis, especially in the most severe forms, but represents a challenge. Previous genome-wide association studies (GWAS) made no distinction between peritoneal endometriosis (SUP), endometrioma (OMA), and deep infiltrating endometriosis (DIE). We therefore conducted a pooled sample-based GWAS and distinguished histologically confirmed endometriosis subtypes. We performed an initial discovery step on 10-individual pools (two pools per condition). After quality control filtering, a Monte-Carlo simulation w

View details →
Negative / Null Result ReportOpen accessMedicine

Morphologic remission status is limited compared to ΔN flow cytometry: a Children’s Oncology Group AAML0531 report

Lisa Eidenschink Brodersen, Robert B. Gerbing, María Laura Pardo et al. · 2020 · Blood Advances

Risk stratification for acute myeloid leukemia (AML) uses molecular and cytogenetic abnormalities identified at diagnosis. Response to therapy informs risk, and morphology continues to be used more frequently than flow cytometry. Herein,…

View details →
Negative / Null Result ReportMedicine

A Replication Study for Association of 53 Single Nucleotide Polymorphisms in ScoliScore Test With Adolescent Idiopathic Scoliosis in French-Canadian Population

Qi Tang, Cédric Julien, Robert Eveleigh et al. · 2015 · Spine

In Brief Study Design. A replication association study that used genomic data generated from French-Canadian case and control cohorts. Objectives. To determine whether the 53 single nucleotide polymorphisms (SNPs) that were previously…

View details →
Negative / Null Result ReportOpen accessMedicine

Proactive vs Reactive Treatment of Hypotension During Surgery

Matthijs Kant, Wilton A. van Klei, Markus W. Hollmann et al. · 2025 · JAMA

Importance: Intraoperative hypotension is associated with adverse postoperative outcomes, but whether a proactive strategy to prevent intraoperative hypotension improves outcomes is uncertain. Objective: To determine whether intraoperative…

View details →
Negative / Null Result ReportOpen accessMedicine

From bench to bedside: translating mesenchymal stem cell therapies through preclinical and clinical evidence

Jai Chand Patel, Meenakshi Shukla, Manish Shukla et al. · 2025 · Frontiers in Bioengineering and Biotechnology

Mesenchymal stem cells (MSCs) are emerging as a powerful tool in regenerative medicine due to their ability to differentiate into mesenchymal lineages, such as bone, cartilage, and fat, along with their low immunogenicity and strong immunomodulatory properties. Unlike traditional cell therapies that rely on engraftment, MSCs primarily function through paracrine signaling-secreting bioactive molecules like vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), and exosomes. These factors contribute to tissue repair, promote angiogenesis, and modulate immune response

View details →
Negative / Null Result ReportOpen accessMedicine

Ferroptosis is a targetable detrimental factor in metabolic dysfunction-associated steatotic liver disease

Cédric Peleman, Stig Hellemans, Geraldine Veeckmans et al. · 2024 · Cell Death and Differentiation

There is an unmet clinical need for pharmacologic treatment for metabolic dysfunction-associated steatotic liver disease (MASLD). Hepatocyte cell death is a hallmark of this highly prevalent chronic liver disease, but the dominant type of cell death remains uncertain. Here we report that ferroptosis, an iron-catalyzed mode of regulated cell death, contributes to MASLD. Unsupervised clustering in a cohort of biopsy-proven MASLD patients revealed a subgroup with hepatic ferroptosis signature and lower glutathione peroxidase 4 (GPX4) levels. Likewise, a subgroup with reduced ferroptosis defenses

View details →
Negative / Null Result ReportOpen accessMedicine

Exploring the lung-gut direction of the gut-lung axis in patients with ARDS

Mairi Ziaka, Aristomenis K. Exadaktylos · 2024 · Critical Care

Acute respiratory distress syndrome (ARDS) represents a life-threatening inflammatory reaction marked by refractory hypoxaemia and pulmonary oedema. Despite advancements in treatment perspectives, ARDS still carries a high mortality rate, often due to systemic inflammatory responses leading to multiple organ dysfunction syndrome (MODS). Indeed, the deterioration and associated mortality in patients with acute lung injury (LI)/ARDS is believed to originate alongside respiratory failure mainly from the involvement of extrapulmonary organs, a consequence of the complex interaction between initial

View details →
Negative / Null Result ReportOpen accessMedicine

Significant association between urethral length measured by magnetic resonance imaging and urinary continence recovery after robot-assisted radical prostatectomy

Kosuke Kitamura, Toshiyuki China, Mayuko Kanayama et al. · 2018 · Prostate International

To determine the clinical predictive factors affecting the recovery from postoperative urinary incontinence after robot-assisted radical prostatectomy (RARP). We consecutively analyzed 320 patients who underwent RARP between January 2012…

View details →
Negative / Null Result ReportOpen accessMedicine

Is niacin ineffective? Or did AIM-HIGH miss its target?

Stephen J. Nicholls · 2012 · Cleveland Clinic Journal of Medicine

The AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) found, in an interim analysis, no cardiovascular benefit from taking extended-release niacin…

View details →