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BMC Nephrology May 2024Fruquintinib is a highly selective inhibitor of vascular endothelial growth factor receptor (VEGFR). Currently, there are no reported cases of fruquintinib causing...
BACKGROUND
Fruquintinib is a highly selective inhibitor of vascular endothelial growth factor receptor (VEGFR). Currently, there are no reported cases of fruquintinib causing kidney-restrictive thrombotic microangiopathy (TMA) in the available Chinese and foreign literature.
CASE PRESENTATION
In this case report, we presented a 73-year-old patient receiving fruquintinib for metastatic colon cancer, manifesting abundant proteinuria, in which kidney-restrictive TMA was also diagnosed through renal biopsy. As far as we were concerned, this was the frst reported in terms of fruquintinib-induced kidney-restrictive TMA confrmed by renal biopsy.
CONCLUSION
This case indicates that fruquintinib may result in kidney-restrictive TMA, which is a rare but life-threatening complication of cancer treatment drug. Therefore, regular monitoring of proteinuria and blood pressure is imperative for all patients undergoing anti-VEGF drug therapy. And renal biopsy should be promptly conducted to facilitate early detection of thrombotic microangiopathy.
Topics: Humans; Thrombotic Microangiopathies; Aged; Male; Colonic Neoplasms; Quinazolines
PubMed: 38762494
DOI: 10.1186/s12882-024-03598-8 -
Life Science Alliance Aug 2024Dynamic rearrangements of the F-actin cytoskeleton are a hallmark of tumor metastasis. Thus, proteins that govern F-actin rearrangements are of major interest for...
Dynamic rearrangements of the F-actin cytoskeleton are a hallmark of tumor metastasis. Thus, proteins that govern F-actin rearrangements are of major interest for understanding metastasis and potential therapies. We hypothesized that the unique F-actin binding and bundling protein SWAP-70 contributes importantly to metastasis. Orthotopic, ectopic, and short-term tail vein injection mouse breast and lung cancer models revealed a strong positive dependence of lung and bone metastasis on SWAP-70. Breast cancer cell growth, migration, adhesion, and invasion assays revealed SWAP-70's key role in these metastasis-related cell features and the requirement for SWAP-70 to bind F-actin. Biophysical experiments showed that tumor cell stiffness and deformability are negatively modulated by SWAP-70. Together, we present a hitherto undescribed, unique F-actin modulator as an important contributor to tumor metastasis.
Topics: Animals; Actins; Mice; Humans; Female; Cell Line, Tumor; Neoplasm Metastasis; Breast Neoplasms; Lung Neoplasms; Microfilament Proteins; Cell Movement; Actin Cytoskeleton; Cell Proliferation; Cell Adhesion; Protein Binding
PubMed: 38760173
DOI: 10.26508/lsa.202302307 -
BMJ Open May 2024DNA-informed prescribing (termed pharmacogenomics, PGx) is the epitome of personalised medicine. Despite international guidelines existing, its implementation in...
Minimising Adverse Drug Reactions and Verifying Economic Legitimacy-Pharmacogenomics Implementation in Children (MARVEL- PIC): protocol for a national randomised controlled trial of pharmacogenomics implementation.
INTRODUCTION
DNA-informed prescribing (termed pharmacogenomics, PGx) is the epitome of personalised medicine. Despite international guidelines existing, its implementation in paediatric oncology remains sparse.
METHODS AND ANALYSIS
Minimising Adverse Drug Reactions and Verifying Economic Legitimacy-Pharmacogenomics Implementation in Children is a national prospective, multicentre, randomised controlled trial assessing the impact of pre-emptive PGx testing for actionable PGx variants on adverse drug reaction (ADR) incidence in patients with a new cancer diagnosis or proceeding to haematopoetic stem cell transplant. All ADRs will be prospectively collected by surveys completed by parents/patients using the National Cancer Institute Pediatric Patient Reported [Ped-PRO]-Common Terminology Criteria for Adverse Events (CTCAE) (weeks 1, 6 and 12). Pharmacist will assess for causality and severity in semistructured interviews using the CTCAE and Liverpool Causality Assessment Tool. The primary outcome is a reduction in ADRs among patients with actionable PGx variants, where an ADR will be considered as any CTCAE grade 2 and above for non-haematological toxicities and any CTCAE grade 3 and above for haematological toxicities Cost-effectiveness of pre-emptive PGx (secondary outcome) will be compared with standard of care using hospital inpatient and outpatient data along with the validated Childhood Health Utility 9D Instrument. Power and statistics considerations: A sample size of 440 patients (220 per arm) will provide 80% power to detect a 24% relative risk reduction in the primary endpoint of ADRs (two-sided α=5%, 80% vs 61%), allowing for 10% drop-out.
ETHICS AND DISSEMINATION
The ethics approval of the trial has been obtained from the Royal Children's Hospital Ethics Committee (HREC/89083/RCHM-2022). The ethics committee of each participating centres nationally has undertaken an assessment of the protocol and governance submission.
TRIAL REGISTRATION NUMBER
NCT05667766.
Topics: Humans; Child; Drug-Related Side Effects and Adverse Reactions; Pharmacogenetics; Prospective Studies; Randomized Controlled Trials as Topic; Neoplasms; Multicenter Studies as Topic; Precision Medicine; Hematopoietic Stem Cell Transplantation
PubMed: 38760050
DOI: 10.1136/bmjopen-2024-085115 -
BMJ Open May 2024The administration of immune checkpoint inhibitors (ICIs) may lead to renal adverse events, notably including renal dysfunction. To early predict the probability of...
Development and validation of a nomogram for predicting the occurrence of renal dysfunction after treatment of immune checkpoint inhibitor: a retrospective case-control study.
PURPOSE
The administration of immune checkpoint inhibitors (ICIs) may lead to renal adverse events, notably including renal dysfunction. To early predict the probability of renal dysfunction after ICIs therapy, a retrospective case-control study was conducted.
METHODS
Clinical information on ICIs-treated patients was collected. Multivariable logistic regression was applied to identify risk factors for renal dysfunction after ICIs treatment. Moreover, a nomogram model was developed and validated internally.
RESULTS
A total of 442 patients were included, among which 35 (7.9%) experienced renal dysfunction after ICIs treatment. Lower baseline estimated glomerular filtration rate (eGFR) (OR 0.941; 95% CI 0.917 to 0.966; p<0.001), concurrent exposure of platinum(OR 4.014; 95% CI 1.557 to 10.346; p=0.004), comorbidities of hypertension (OR 3.478; 95% CI 1.600 to 7.562; p=0.002) and infection (OR 5.402; 95% CI 1.544 to 18.904; p=0.008) were found to be independent associated with renal dysfunction after ICIs treatment. To develop a predictive nomogram for the occurrence of renal dysfunction after ICIs treatment, the included cases were divided into training and validation groups in a ratio of 7:3 randomly. The above four independent risk factors were included in the model. The area under the receiver operating characteristic curves of the predictiive model were 0.822 (0.723-0.922) and 0.815 (0.699-0.930) in the training and validation groups, respectively.
CONCLUSIONS
Lower baseline eGFR, platinum exposure, comorbidities of hypertension and infection were predictors of renal dysfunction in ICIs-treated patients with cancer. A nomogram was developed to predict the probability of renal dysfunction after ICIs treatment, which might be operable and valuable in clinical practice.
Topics: Humans; Nomograms; Male; Female; Retrospective Studies; Immune Checkpoint Inhibitors; Middle Aged; Case-Control Studies; Aged; Glomerular Filtration Rate; Risk Factors; Logistic Models; Neoplasms; Renal Insufficiency; Kidney Diseases
PubMed: 38760047
DOI: 10.1136/bmjopen-2023-082484 -
BMJ Open May 2024Extrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant... (Review)
Review
INTRODUCTION
Extrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant pleural tumours such as pleural mesothelioma, non-mesothelioma pleural malignancies such as thymoma and sarcoma, and rarely for pleural tuberculosis, in a more limited fashion. Despite extensive studies on both surgical techniques and consequences, a significant knowledge gap remains regarding how best to approach the perioperative anaesthesia challenges for EPP and ePD.It is unknown if the risk stratification processes for such surgeries are standardised or what types of functional and dynamic cardiac and pulmonary tests are employed preoperatively to assist in the perioperative risk stratification. Further, it is unknown whether the types of anaesthesia and analgesia techniques employed, and the types of haemodynamic monitoring tools used, impact on outcomes. It is also unknown whether individualised haemodynamic protocols are used to guide the rational use of fluids, vasoactive drugs and inotropes.Finally, there is a dearth of evidence regarding how best to monitor these patients postoperatively or what the most effective enhanced recovery protocols are to best mitigate postoperative complications and accelerate hospital discharge. To increase our knowledge of the perioperative and anaesthetic treatment for patients undergoing EPP/ePD, this scoping review attempts to synthesise the literature and identify these knowledge gaps.
METHODS AND ANALYSIS
This scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Review Protocols methodology. Electronic databases, OVID Medline, EMBASE and the Cochrane Library, will be systematically searched for relevant literature corresponding to EPP or ePD and perioperative or anaesthetic management. Data will be analysed and summarised descriptively and organised according to the three perioperative stages: preoperative, intraoperative and postoperative factors in clinical care.
ETHICS AND DISSEMINATION
Ethics approval was not required. The findings will be disseminated through professional networks, conference presentations and publications in scientific journals.
Topics: Humans; Pneumonectomy; Anesthesia; Pleura; Perioperative Care; Pleural Neoplasms; Postoperative Complications
PubMed: 38760041
DOI: 10.1136/bmjopen-2023-078125 -
BMJ Open May 2024The aim of this study was to map and compare stakeholders' perceptions of barriers towards cervical cancer screening for vulnerable women in seven European countries. (Comparative Study)
Comparative Study
OBJECTIVES
The aim of this study was to map and compare stakeholders' perceptions of barriers towards cervical cancer screening for vulnerable women in seven European countries.
DESIGN
In Collaborative User Boards, stakeholders were invited to participate to identify barriers towards participation in cervical cancer screening.
SETTING
The study is nested in the European Union-funded project CBIG-SCREEN which aims to tackle inequity in cervical cancer screening for vulnerable women (www.cbig-screen.eu). Data collection took place in Bulgaria, Denmark, Estonia, France, Italy, Portugal and Romania.
PARTICIPANTS
Participants represented micro-level stakeholders covering representatives of users, that is, vulnerable women, meso-level stakeholders covering healthcare professionals and social workers, and macro-level stakeholders covering programme managers and decision-makers.
METHODS
Across the seven countries, 25 meetings in Collaborative User Boards with a duration of 2 hours took place between October 2021 and June 2022. The meetings were video recorded or audio recorded, transcribed and translated into English for a qualitative framework analysis.
RESULTS
120 participants took part in the Collaborative User Boards. Context-specific barriers were related to different healthcare systems and characteristics of vulnerable populations. In Romania and Bulgaria, the lack of a continuous screening effort and lack of ways to identify eligible women were identified as barriers for all women rather than being specific for women in vulnerable situations. The participants in Denmark, Estonia, France, Italy and Portugal identified providers' lack of cultural and social sensitivity towards vulnerable women as barriers. In all countries, vulnerable women's fear, shame and lack of priority to preventive healthcare were identified as psychological barriers.
CONCLUSION
The study provides an overview of stakeholders' perceived barriers towards vulnerable women's cervical cancer screening participation in seven European countries. The organisation of healthcare systems and the maturity of screening programmes differ between countries, while vulnerable women's psychological barriers had several similarities.
Topics: Humans; Female; Uterine Cervical Neoplasms; Early Detection of Cancer; Europe; Vulnerable Populations; Qualitative Research; Adult; Middle Aged; Patient Acceptance of Health Care; Stakeholder Participation; Health Services Accessibility
PubMed: 38760040
DOI: 10.1136/bmjopen-2023-079921 -
BMJ Open May 2024Recruiting to randomised trials is often challenging particularly when the intervention arms are markedly different. The Mesothelioma and Radical Surgery 2 randomised... (Randomized Controlled Trial)
Randomized Controlled Trial
Strategies to address recruitment to a randomised trial of surgical and non-surgical treatment for cancer: results from a complex recruitment intervention within the Mesothelioma and Radical Surgery 2 (MARS 2) study.
OBJECTIVES
Recruiting to randomised trials is often challenging particularly when the intervention arms are markedly different. The Mesothelioma and Radical Surgery 2 randomised controlled trial (RCT) compared standard chemotherapy with or without (extended) pleurectomy decortication surgery for malignant pleural mesothelioma. Anticipating recruitment difficulties, a QuinteT Recruitment Intervention was embedded in the main trial phase to unearth and address barriers. The trial achieved recruitment to target with a 4-month COVID-19 pandemic-related extension. This paper presents the key recruitment challenges, and the strategies delivered to optimise recruitment and informed consent.
DESIGN
A multifaceted, flexible, mixed-method approach to investigate recruitment obstacles drawing on data from staff/patient interviews, audio recorded study recruitment consultations and screening logs. Key findings were translated into strategies targeting identified issues. Data collection, analysis, feedback and strategy implementation continued cyclically throughout the recruitment period.
SETTING
Secondary thoracic cancer care.
RESULTS
Respiratory physicians, oncologists, surgeons and nursing specialists supported the trial, but recruitment challenges were evident. The study had to fit within a framework of a thoracic cancer service considered overstretched where patients encountered multiple healthcare professionals and treatment views, all of which challenged recruitment. Clinician treatment biases, shaped in part by the wider clinical and research context alongside experience, adversely impacted several aspects of the recruitment process by restricting referrals for study consideration, impacting eligibility decisions, affecting the neutrality in which the study and treatment was presented and shaping patient treatment expectations and preferences. Individual and group recruiter feedback and training raised awareness of key equipoise issues, offered support and shared good practice to safeguard informed consent and optimise recruitment.
CONCLUSIONS
With bespoke support to overcome identified issues, recruitment to a challenging RCT of surgery versus no surgery in a thoracic cancer setting with a complex recruitment pathway and multiple health professional involvement is possible.
TRIAL REGISTRATION NUMBER
ISRCTN ISRCTN44351742, Clinical Trials.gov NCT02040272.
Topics: Humans; Patient Selection; Mesothelioma; COVID-19; Mesothelioma, Malignant; Pleural Neoplasms; Randomized Controlled Trials as Topic; Lung Neoplasms; SARS-CoV-2; Informed Consent; Female; Male
PubMed: 38760029
DOI: 10.1136/bmjopen-2023-079108 -
Cancer Control : Journal of the Moffitt... 2024
Topics: Humans; Head and Neck Neoplasms; Periodontal Diseases; Radiotherapy; Radiation Injuries
PubMed: 38760005
DOI: 10.1177/10732748241255845 -
Endoscopy Dec 2024
Topics: Humans; Gastrostomy; Esophageal Neoplasms; Male; Gastropexy; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Middle Aged; Aged
PubMed: 38759974
DOI: 10.1055/a-2316-1067 -
Endoscopy Dec 2024
Topics: Humans; Gastric Outlet Obstruction; Self Expandable Metallic Stents; Stomach Neoplasms; Suture Techniques; Foreign-Body Migration; Male; Aged; Female
PubMed: 38759971
DOI: 10.1055/a-2313-3869