e-ISSN: Pending

Browse the failure-mode index

12,368 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.

Negative / Null Result ReportOpen accessMedicine

Preclinical ex vivo and in vivo models to study immunotherapy agents and their combinations as predictive tools toward the clinic

Iñaki Eguren‐Santamaría, Ignacio Melero, Inmaculada Rodríguez et al. · 2025 · Journal for ImmunoTherapy of Cancer

Almost every successful anticancer treatment has been preceded by preclinical scientific breakthroughs that encouraged clinical development. However, therapeutic strategies showing promising preclinical results often fail to confirm…

View details →
Negative / Null Result ReportOpen accessMedicine

Bilateral hip exoskeleton assistance enables faster walking in individuals with chronic stroke-related gait impairments

Chiara Livolsi, R. Conti, Tommaso Ciapetti et al. · 2025 · Scientific Reports

Millions of individuals surviving a stroke have lifelong gait impairments that reduce their personal independence and quality of life. Reduced walking speed is one of the major problems limiting community mobility and reintegration. Previous studies have shown positive effect of robot-assisted gait training utilizing hip exoskeletons for individuals with gait impairments due to a stroke, leading to increased walking speed in post-treatment compared to pre-treatment assessments. However, no evidence emerged of a significant increasing in walking speed attributable to device usage compared to wa

View details →
Negative / Null Result ReportOpen accessMedicine

Associations of High-Sensitivity Cardiac Troponin T, D-Dimer, and N-Terminal Pro–B-Type Natriuretic Peptide with Subclinical Cardiovascular Dysfunction in the General Population: A Retrospective Cross-Sectional Study

Grzegorz K. Jakubiak, Natalia Pawlas, Monika Starzak et al. · 2026 · Vascular Health and Risk Management

Purpose: The purpose of this study was to analyze the relationship between resting high-sensitive serum cardiac troponin T concentration (hs-cTnT), D-dimer, and N-terminal pro–B-type natriuretic peptide (NT-proBNP), measured outside the…

View details →
Negative / Null Result ReportOpen accessMedicine

Impact of a Symptom Checker App on Patient-Physician Interaction Among Self-Referred Walk-In Patients in the Emergency Department: Multicenter, Parallel-Group, Randomized, Controlled Trial

Malte L Schmieding, Marvin Kopka, Myrto Bolanaki et al. · 2025 · Journal of Medical Internet Research

BACKGROUND: Symptom checker apps (SCAs) are layperson-facing tools that advise on whether and where to seek care, or possible diagnoses. Previous research has primarily focused on evaluating the accuracy, safety, and usability of their recommendations. However, studies examining SCAs' impact on clinical care, including the patient-physician interaction and satisfaction with care, remain scarce. OBJECTIVE: This study aims to evaluate the effects of an SCA on satisfaction with the patient-physician interaction in acute care settings. Additionally, we examined its influence on patients' anxiety a

View details →
Negative / Null Result ReportOpen accessMedicine

Meningioma: Novel Diagnostic and Therapeutic Approaches

Carlen Yuen, Michelle Zheng, Max Saint-Germain et al. · 2025 · Biomedicines

Background/Objectives: Meningiomas are the most common intracranial tumors. Surgery and radiation therapy are the cornerstones of treatment and no standard of care therapy exists for refractory meningiomas. This manuscript aims to provide a comprehensive review of novel diagnostic and therapeutic approaches against these tumors. Methods: A search for the existing literature on systemic therapies for meningiomas was performed on PubMed and a search for presently accruing clinical trials was performed on ClinicalTrials.gov. Results: Systemic treatments, including chemotherapy, somatostatin analo

View details →
Negative / Null Result ReportOpen accessMedicine

Identifying SCS Trial Responders Immediately After Postoperative Programming with ECAP Dose-Controlled Closed-Loop Therapy

Jason E. Pope, Ajay Antony, Erika Petersen et al. · 2024 · Pain and Therapy

INTRODUCTION: Drawbacks of fixed-output spinal cord stimulation (SCS) screening trials may lead to compromised trial outcomes and poor predictability of long-term success. Evoked compound action potential (ECAP) dose-controlled closed-loop…

View details →
Negative / Null Result ReportOpen accessMedicine

Randomized Phase II/III Trial Comparing Hepatectomy, Followed by mFOLFOX6 With Hepatectomy Alone for Liver Metastasis From Colorectal Cancer: Long-Term Results of JCOG0603

Y. Kanemitsu, Yasuhiro Shimizu, Junki Mizusawa et al. · 2026 · Journal of Clinical Oncology

JCOG0603 demonstrated improved disease-free survival (DFS) with adjuvant mFOLFOX6 after hepatectomy compared with hepatectomy alone in colorectal liver-only metastasis (CRLM), but the overall survival (OS) data were immature. Here, we…

View details →
Replication FailureOpen accessMedicine

Randomized trial investigating the utility of a liver tissue transcriptional biomarker in identifying adult liver transplant recipients not requiring maintenance immunosuppression

Julien Vionnet, Jorge P. Torres-Yaguana, Rosa Miquel et al. · 2024 · American Journal of Transplantation

The maintenance of stable allograft status in the absence of immunosuppression (IS), known as operational tolerance, can be achieved in a small proportion of liver transplant recipients, but we lack reliable tools to predict its spontaneous development. We conducted a prospective, multicenter, biomarker-strategy design, IS withdrawal clinical trial to determine the utility of a predictive biomarker of operational tolerance. The biomarker test, originally identified in a patient cohort with high operational tolerance prevalence, consisted of a 5-gene transcriptional signature measured in liver

View details →
Negative / Null Result ReportOpen accessMedicine

Amyloid-beta-targeting monoclonal antibodies for people with mild cognitive impairment or mild dementia due to Alzheimer’s disease

Francesco Nonino, Silvia Minozzi, L. Sambati et al. · 2026 · Cochrane Database of Systematic Reviews

RATIONALE: Alzheimer's disease is a neurodegenerative disorder and the most common cause of dementia. Aggregated amyloid-beta protein deposits are implicated in its pathogenesis. Amyloid-beta-targeting monoclonal antibodies (sometimes represented as Aβ-mAbs) are potentially disease-modifying for Alzheimer's disease: through the clearance of amyloid in the brain, they may slow cognitive and functional decline. OBJECTIVES: To assess the clinical benefits and harms of amyloid-beta-targeting monoclonal antibodies aducanumab, bapineuzumab, crenezumab, donanemab, gantenerumab, lecanemab, ponezumab,

View details →
Negative / Null Result ReportOpen accessMedicine

Efficacy and Safety of Digitalis Glycosides in Heart Failure

Kevin Damman, Dirk J. van Veldhuisen, Johann Bauersachs et al. · 2026 · JAMA

Importance: Digitalis glycosides may be used as additional therapy in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HF with reduced EF (HFrEF). Objective: To assess the effect of digitalis glycosides on…

View details →
Negative / Null Result ReportOpen accessMedicine

Suzetrigine (VX-548) exhibits activity-dependent effects on human dorsal root ganglion neurons with differential pain etiology

Megan L. Uhelski, Mandee K. Schaub, Felipe Espinosa et al. · 2026 · Pain

ABSTRACT: Nonselective antagonists of voltage-gated sodium channels (VGSCs) provide effective local analgesia, but systemic administration is fraught with unwanted cardiovascular and central nervous system toxicity. The development of…

View details →
Negative / Null Result ReportOpen accessMedicine

GLP-1 and the cardiovascular system

Florian Kahles, Andreas L. Birkenfeld, Nikolaus Marx · 2026 · Journal of Clinical Investigation

The incretin hormone glucagon-like peptide-1 (GLP-1) exerts potent effects on glucose metabolism, prompting the development of therapeutic strategies that enhance activity of the GLP-1 receptor (GLP-1R) pathway. Inhibitors of dipeptidyl peptidase 4 (DPP-4) prolong the half-life of endogenous GLP-1 and typically achieve reductions in HbA1c of 0.5%-0.8%. However, large-scale cardiovascular (CV) outcomes trials (CVOTs) with DPP-4 inhibitors demonstrated CV safety but did not show a reduction in CV events. A second incretin-based therapeutic approach was the development of GLP-1R agonists (GLP-1RA

View details →
Negative / Null Result ReportOpen accessMedicine

An international Phase IV field study - psychometric properties of the updated module on assessing quality of life of patients with breast cancer EORTC QLQ-BR42

Vesna Bjelic‐Radisic, Fátima Cardoso, Joachim Weis et al. · 2025 · The Breast

BACKGROUND: The EORTC QLQ-BR23, published in 1996, was one of the first disease-specific questionnaires to assess health-related quality of life (HRQoL) in patients with breast cancer (BC). In the last decades, major changes in BC…

View details →
Negative / Null Result ReportOpen accessMedicine

Lactiplantibacillus plantarum 299v supplementation modulates β-cell ER stress and antioxidative defense pathways and prevents type 1 diabetes in gluten-free BioBreeding rats

Pinar Sargin, Mark F. Roethle, Shuang Jia et al. · 2022 · Gut Microbes

The increasing incidence of Type 1 diabetes has coincided with the emergence of the low-fiber, high-gluten Western diet and other environmental factors linked to dysbiosis. Since Lactiplantibacillus plantarum 299 v (Lp299v) supplementation improves gut barrier function and reduces systemic inflammation, we studied its effects in spontaneously diabetic DRlyp/lyp rats provided a normal cereal diet (ND) or a gluten-free hydrolyzed casein diet (HCD). All rats provided ND developed diabetes (62.5±7.7 days); combining ND with Lp299v did not improve survival. Diabetes was delayed by HCD (72.2±9.4 day

View details →
Negative / Null Result ReportOpen accessMedicine

PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2

Marwah Karim, Manjari Mishra, Chieh‐Wen Lo et al. · 2025 · Nature Communications

In search for broad-spectrum antivirals, we discover a small molecule inhibitor, RMC-113, that potently suppresses the replication of multiple RNA viruses including SARS-CoV-2 in human lung organoids. We demonstrate selective inhibition of…

View details →
Replication FailureOpen accessMedicine

Genome-wide association study of idiopathic pulmonary fibrosis susceptibility using clinically curated European ancestry datasets

Daniel Chin, Tamara Hernández-Beeftink, Lauren J. Donoghue et al. · 2026 · European Respiratory Journal

ABSTRACT Background Idiopathic pulmonary fibrosis (IPF) is a rare, incurable lung disease with a median survival of 3-5 years after diagnosis. Treatment options are limited. Genetic association studies can identify new genes involved in disease that might represent potential new drug targets, and it has been shown that drug targets with support from genetic studies are more likely to be successful in clinical development. Previous genome-wide association studies (GWAS) of IPF susceptibility have identified more than 20 signals implicating genes involved in multiple mechanisms, including telome

View details →
Negative / Null Result ReportOpen accessMedicine

A large language model for complex cardiology care

Jack W. O’Sullivan, Anil Palepu, Khaled Saab et al. · 2026 · Nature Medicine

The scarcity of subspecialist medical expertise poses a considerable challenge for healthcare delivery. This issue is particularly acute in cardiology, where timely, accurate management determines outcomes. We explored the potential of Articulate Medical Intelligence Explorer (AMIE), a large language model-based experimental medical artificial intelligence system, to augment clinical decision-making in this challenging context. We conducted a randomized controlled trial comparing large language model-assisted care with the usual care of complex patients suspected of having a genetic cardiomyop

View details →
Negative / Null Result ReportOpen accessMedicine

Integration of Artificial Intelligence-Enhanced Capsule Endoscopy in Clinical Practice: A Review of Market-Available Tools for Clinical Practice

A. Giordano, Cristina Romero-Mascarell, Begoña González-Suárez et al. · 2025 · Digestive Diseases and Sciences

The integration of artificial intelligence (AI) into capsule endoscopy is transforming gastrointestinal diagnostics by enhancing lesion detection and optimizing reading efficiency. This review focuses on the clinical applications of…

View details →
Negative / Null Result ReportOpen accessMedicine

Climate change and hyponatremia‐related hospital admissions in people with focal epilepsy exposed to carbamazepine or its derivatives

Francesco Fortunato, Francesco D’Amico, Anny Votano et al. · 2025 · Epilepsia

OBJECTIVE: To estimate the proportion of individuals with focal epilepsy treated with at least one among carbamazepine (CBZ), oxcarbazepine (OXC), or eslicarbazepine (ESL), who were hospitalized due to hyponatremia-related symptoms in 2024, and to test the hypothesis that there is an association with climatic variables. METHODS: We undertook a prospective study in which people with focal epilepsy treated with at least one of the target drugs and at least one attendance in 2024 formed the study cohort. Individuals who were admitted or seen as outpatients for hyponatremia in 2024 were considered

View details →
Negative / Null Result ReportOpen accessMedicine

Comparison of Deep Learning and Clinician Performance for Detecting Referable Glaucoma from Fundus Photographs in a Safety Net Population

Van Nguyen, Sreenidhi Iyengar, Haroon Rasheed et al. · 2025 · Ophthalmology Science

Purpose Develop and test a deep learning (DL) algorithm for detecting referable glaucoma. Design Retrospective cohort study. Participants A total of 6116 patients from the Los Angeles County (LAC) Department of Health Services (DHS) were…

View details →
Negative / Null Result ReportOpen accessMedicine

Cell Migration–Proliferation Dichotomy in Cancer: Biological Fact or Experimental Artefact?

Abdulaziz Alfahed · 2024 · Biology

The migration-proliferation dichotomy (MPD) has long been observed in cultured cancer cells. This phenomenon is not only relevant to tumour progression but may also have therapeutic significance in clinical cancer. However, MPD has rarely been investigated in primary cancer. This study aimed to either confirm or disprove the existence of MPD in primary cancer. Using primary gastric, colorectal and prostate cancer (GC, CRC and PCa) cohorts from the Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center, this study interrogated the MPD phenomenon by utilising RNA-Seq-based proliferation

View details →
Negative / Null Result ReportOpen accessMedicine

Neonatal Respiratory Outcomes in Placenta Previa with Histopathologically Confirmed Placenta Accreta Spectrum

Marta Młodawska, Anna Zmelonek-Znamirowska, Grzegorz Świercz et al. · 2026 · Journal of Clinical Medicine

Background and Objectives: Placenta accreta spectrum (PAS) complicating placenta praevia is associated with increased maternal morbidity; however, neonatal respiratory burden may be underappreciated. We compared neonatal outcomes between pregnancies complicated by placenta praevia with and without histopathologically confirmed PAS, with additional adjustment of respiratory outcomes for gestational age at delivery. Materials and Methods: We conducted a retrospective single-centre cohort study (n = 82). Based on placental histopathology, women were classified as PAS (n = 37; accreta/increta/perc

View details →
Negative / Null Result ReportOpen accessMedicine

The role of microbiota dysbiosis in Parkinson’s disease: Pathophysiology and therapeutic opportunities

Shabnam Santos, Ivonne Salinas, Nicolás Almeida et al. · 2025 · Engineering Microbiology

ABSTRACT Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder characterized by debilitating motor and non-motor symptoms. Its etiology is multifactorial, with no single definitive cause identified, although aging…

View details →
Replication FailureOpen accessMedicine

Tavapadon as Adjunctive Treatment for Parkinson Disease

Hubert H. Fernandez, S. H. Isaacson, Robert A. Hauser et al. · 2026 · JAMA Neurology

Importance: Development of motor fluctuations is common in people with Parkinson disease (PD) treated with oral levodopa, and currently available dopamine (D) agonists adjunctive to levodopa offer additional motor control but may increase…

View details →
Replication FailureOpen accessMedicine

Transarterial chemoembolization plus atezolizumab and bevacizumab in patients with intermediate hepatocellular carcinoma: a single-arm, phase 2 trial

Kang Wang, Jinkai Feng, Hongming Yu et al. · 2025 · Signal Transduction and Targeted Therapy

Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC), yet its efficacy as a standalone therapy remains suboptimal. This phase 2 trial (ChiCTR2100049829) evaluated the feasibility and safety of TACE combined with atezolizumab and bevacizumab in patients with intermediate-stage HCC. Participants received TACE followed by atezolizumab and bevacizumab until disease progression, unacceptable toxicity, or death. The primary endpoint was objective response rate (ORR) assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1

View details →
Negative / Null Result ReportOpen accessMedicine

The impact of p53 mutation on tumor immune evasion: mechanistic insights and clinical implications

L. Liang, Weidong Wang · 2026 · Frontiers in Immunology

Mutant p53(Mtp53) not only loses its canonical tumor-suppressive functions but also acquires oncogenic gain-of-function properties, positioning it as a central orchestrator in reshaping the tumor immune microenvironment. This review systematically delineates how Mtp53 actively establishes and sustains an immunosuppressive niche through multiple interconnected mechanisms, including chronic inflammation, immune cell dysfunction, reprogramming of cancer-associated fibroblasts, metabolic dysregulation, epigenetic hijacking, and potentially aberrant liquid–liquid phase separation, thereby promoting

View details →