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BMC Cancer Jun 2024Checkpoint inhibitors (CPIs) are widely used in cancer treatment, with transformative impacts on survival. They nonetheless carry a significant risk of toxicity in the... (Observational Study)
Observational Study
BACKGROUND
Checkpoint inhibitors (CPIs) are widely used in cancer treatment, with transformative impacts on survival. They nonetheless carry a significant risk of toxicity in the form of immune-related adverse events (IrAEs), which may be sustained and life-altering. IrAEs may require high-dose and/or prolonged steroid use and represent a significant healthcare burden. They mimic immune-mediated inflammatory diseases (IMIDs) but understanding of their pathogenesis is limited. The MEDALLION project aims to determine targetable mechanisms of immune dysregulation in IrAE development, employing an immune monitoring approach to determine changes in circulating and tissue resident cells of CPI recipients who do/do not develop them and assessing the contribution of the microbiome in parallel.
METHODS
MEDALLION is a non-randomised longitudinal cohort study aiming to recruit 66 cancer patient recipients of anti-PD1/PD-L1, anti-CTLA-4 or combination therapy. Eligible participants include those with malignant melanoma in the adjuvant or metastatic setting, mesothelioma and non-small cell lung carcinoma (NSCLC) treated in the metastatic setting. Comprehensive clinical evaluation is carried out alongside blood, skin swab and stool sampling at the time of CPI initiation (baseline) and during subsequent routine hospital visits on 6 occasions over a 10-month follow-up period. It is conservatively anticipated that one third of enrolled patients will experience a "significant IrAE" (SirAE), defined according to pre-determined criteria specific to the affected tissue/organ system. Those developing such toxicity may optionally undergo a biopsy of affected tissue where appropriate, otherwise being managed according to standard of care. Peripheral blood mononuclear cells will be analysed using multi-parameter flow cytometry to investigate immune subsets, their activation status and cytokine profiles. Stool samples and skin swabs will undergo DNA extraction for 16 S ribosomal RNA (rRNA) sequencing and internal transcribed spacer (ITS) gene sequencing to determine bacterial and fungal microbiome diversity, respectively, including species associated with toxicity. Stored tissue biopsies will be available for in situ and single-cell transcriptomic evaluation. Analysis will focus on the identification of biological predictors and precursors of SirAEs.
DISCUSSION
The pathogenesis of IrAEs will be assessed through the MEDALLION cohort, with the potential to develop tools for their prediction and/or strategies for targeted prevention or treatment.
TRIAL REGISTRATION
The study was registered on 18/09/2023 in the ISRCTN registry (43,419,676).
Topics: Humans; Immune Checkpoint Inhibitors; Neoplasms; Longitudinal Studies; Immunotherapy; Cohort Studies; Monitoring, Immunologic; Melanoma
PubMed: 38877461
DOI: 10.1186/s12885-024-12468-3 -
Technical Innovations & Patient Support... Jun 2024Technological advances in radiation therapy impact on the role and scope of practice of the radiation therapist. The European Society of Radiotherapy and Oncology...
Technological advances in radiation therapy impact on the role and scope of practice of the radiation therapist. The European Society of Radiotherapy and Oncology (ESTRO) recently held two workshops on this topic and this position paper reflects the outcome of this workshop, which included radiation therapists from all global regions. Workflows, quality assurance, research, IGRT and ART as well as clinical decision making are the areas of radiation therapist practice that will be highly influenced by advancing technology in the near future. This position paper captures the opportunities that this will bring to the radiation therapist profession, to the practice of radiation therapy and ultimately to patient care.
PubMed: 38831996
DOI: 10.1016/j.tipsro.2024.100243 -
BMJ Open May 2024The objective of this study is to determine research priorities for the management of major trauma, representing the shared priorities of patients, their families,...
OBJECTIVE
The objective of this study is to determine research priorities for the management of major trauma, representing the shared priorities of patients, their families, carers and healthcare professionals.
DESIGN/SETTING
An international research priority-setting partnership.
PARTICIPANTS
People who have experienced major trauma, their carers and relatives, and healthcare professionals involved in treating patients after major trauma. The scope included chest, abdominal and pelvic injuries as well as major bleeding, multiple injuries and those that threaten life or limb.
METHODS
A multiphase priority-setting exercise was conducted in partnership with the James Lind Alliance over 24 months (November 2021-October 2023). An international survey asked respondents to submit their research uncertainties which were then combined into several indicative questions. The existing evidence was searched to ensure that the questions had not already been sufficiently answered. A second international survey asked respondents to prioritise the research questions. A final shortlist of 19 questions was taken to a stakeholder workshop, where consensus was reached on the top 10 priorities.
RESULTS
A total of 1572 uncertainties, submitted by 417 respondents (including 132 patients and carers), were received during the initial survey. These were refined into 53 unique indicative questions, of which all 53 were judged to be true uncertainties after reviewing the existing evidence. 373 people (including 115 patients and carers) responded to the interim prioritisation survey and 19 questions were taken to a final consensus workshop between patients, carers and healthcare professionals. At the final workshop, a consensus was reached for the ranking of the top 10 questions.
CONCLUSIONS
The top 10 research priorities for major trauma include patient-centred questions regarding pain relief and prehospital management, multidisciplinary working, novel technologies, rehabilitation and holistic support. These shared priorities will now be used to guide funders and teams wishing to research major trauma around the globe.
Topics: Humans; Health Priorities; Surveys and Questionnaires; Research; Multiple Trauma; Wounds and Injuries; Caregivers; Health Personnel; Female; Male
PubMed: 38754886
DOI: 10.1136/bmjopen-2023-083450 -
Archives of Plastic Surgery May 2024Several strategies for the management of venous congestion of the nipple-areola complex (NAC) after reduction mammaplasty have been proposed. Among these, hirudotherapy...
Several strategies for the management of venous congestion of the nipple-areola complex (NAC) after reduction mammaplasty have been proposed. Among these, hirudotherapy represents an ancient but still effective method, even though the risk of infections related to leeches should be considered. We report a peculiar case of breast infection and sepsis after leech therapy in a patient who underwent a reduction mammaplasty. A prompt surgical debridement of the wounds and necrotic tissues associated with targeted antibiotic therapy led to a fast improvement of clinical conditions, and partial preservation of the NAC was obtained. Accurate knowledge of the clinical presentation of soft tissue infections related to leeching allows for an early diagnosis and would serve as a warning for surgeons who approach such breast cosmetic procedures.
PubMed: 38737840
DOI: 10.1055/s-0043-1776696 -
Australian Critical Care : Official... Apr 2024Delivering intensive care therapies concordant with patients' values and preferences is considered gold standard care. To achieve this, healthcare professionals must... (Review)
Review
BACKGROUND
Delivering intensive care therapies concordant with patients' values and preferences is considered gold standard care. To achieve this, healthcare professionals must better understand decision-making processes and factors influencing them.
AIM
The aim of this study was to explore factors influencing decision-making processes about implementing and limiting intensive care therapies.
DESIGN
Systematic integrative review, synthesising quantitative, qualitative, and mixed-methods studies.
METHODS
Five databases were searched (Medline, The Cochrane central register of controlled trials, Embase, PsycINFO, and CINAHL plus) for peer-reviewed, primary research published in English from 2010 to Oct 2022. Quantitative, qualitative, or mixed-methods studies focussing on intensive care decision-making were included for appraisal. Full-text review and quality screening included the Critical Appraisal Skills Program tool for qualitative and mixed methods and the Medical Education Research Quality Instrument for quantitative studies. Papers were reviewed by two authors independently, and a third author resolved disagreements. The primary author developed a thematic coding framework and performed coding and pattern identification using NVivo, with regular group discussions.
RESULTS
Of the 83 studies, 44 were qualitative, 32 quantitative, and seven mixed-methods studies. Seven key themes were identified: what the decision is about; who is making the decision; characteristics of the decision-maker; factors influencing medical prognostication; clinician-patient/surrogate communication; factors affecting decisional concordance; and how interactions affect decisional concordance. Substantial thematic overlaps existed. The most reported decision was whether to withhold therapies, and the most common decision-maker was the clinician. Whether a treatment recommendation was concordant was influenced by multiple factors including institutional cultures and clinician continuity.
CONCLUSION
Decision-making relating to intensive care unit therapy goals is complicated. The current review identifies that breadth of decision-makers, and the complexity of intersecting factors has not previously been incorporated into interventions or considered within a single review. Its findings provide a basis for future research and training to improve decisional concordance between clinicians and patients/surrogates with regards to intensive care unit therapies.
PubMed: 38609749
DOI: 10.1016/j.aucc.2024.02.007 -
European Heart Journal Jun 2024Older patients with non-ST-elevation acute coronary syndrome (NSTEACS) are less likely to receive guideline-recommended care including coronary angiography and... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Older patients with non-ST-elevation acute coronary syndrome (NSTEACS) are less likely to receive guideline-recommended care including coronary angiography and revascularization. Evidence-based recommendations regarding interventional management strategies in this patient cohort are scarce. This meta-analysis aimed to assess the impact of routine invasive vs. conservative management of NSTEACS by using individual patient data (IPD) from all available randomized controlled trials (RCTs) including older patients.
METHODS
MEDLINE, Web of Science and Scopus were searched between 1 January 2010 and 11 September 2023. RCTs investigating routine invasive and conservative strategies in persons >70 years old with NSTEACS were included. Observational studies or trials involving populations outside the target range were excluded. The primary endpoint was a composite of all-cause mortality and myocardial infarction (MI) at 1 year. One-stage IPD meta-analyses were adopted by use of random-effects and fixed-effect Cox models. This meta-analysis is registered with PROSPERO (CRD42023379819).
RESULTS
Six eligible studies were identified including 1479 participants. The primary endpoint occurred in 181 of 736 (24.5%) participants in the invasive management group compared with 215 of 743 (28.9%) participants in the conservative management group with a hazard ratio (HR) from random-effects model of 0.87 (95% CI 0.63-1.22; P = .43). The hazard for MI at 1 year was significantly lower in the invasive group compared with the conservative group (HR from random-effects model 0.62, 95% CI 0.44-0.87; P = .006). Similar results were seen for urgent revascularization (HR from random-effects model 0.41, 95% CI 0.18-0.95; P = .037). There was no significant difference in mortality.
CONCLUSIONS
No evidence was found that routine invasive treatment for NSTEACS in older patients reduces the risk of a composite of all-cause mortality and MI within 1 year compared with conservative management. However, there is convincing evidence that invasive treatment significantly lowers the risk of repeat MI or urgent revascularisation. Further evidence is needed from ongoing larger clinical trials.
Topics: Humans; Conservative Treatment; Acute Coronary Syndrome; Aged; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Myocardial Revascularization; Coronary Angiography; Non-ST Elevated Myocardial Infarction; Female
PubMed: 38596853
DOI: 10.1093/eurheartj/ehae151 -
Journal of Clinical Medicine Feb 2024The medicinal leech has been used in plastic surgery to resolve venous congestion that can threaten the viability of tissue transfer. Within the context of breast... (Review)
Review
The medicinal leech has been used in plastic surgery to resolve venous congestion that can threaten the viability of tissue transfer. Within the context of breast surgery, venous congestion is a pertinent consideration for reconstructive and non-reconstructive breast surgery such as mammoplasty and mastopexy. However, leeching is closely associated with complications such as infection, pain, and anaemia. This is the first systematic review that examines the methodology, efficacy, and post therapeutic outcome data across all existing studies on medicinal leeching in breast surgery. A systematic search of PubMed and Embase databases from their inception to November 2023 was conducted. Inclusion criteria included studies reporting on the use of leeches to resolve venous congestion in any breast surgery. The JBI Critical Appraisal Checklist for Case Series tool was used for bias analysis. Descriptive statistics were undertaken in Microsoft Excel. A total of 18 studies with a combined sample size of 28 were examined, including 4 case series and 14 case reports. Patients mostly underwent reconstructive breast surgery (75%). The median number of leeches used was two, with a median number of three leeching sessions per day and 3 days of leeching. Medicinal leeching successfully prevented the loss of 75% of all tissue transfers. The complication rate was high at 81.14% and mainly included infection and anaemia. Medicinal leeching is an effective method to relieve venous congestion in breast surgery but must be judiciously used within the clinical context of the patient to maximise efficacy and mitigate harm from complications.
PubMed: 38592085
DOI: 10.3390/jcm13051243 -
Medicine Apr 2024Epistaxis is one of the common emergencies in otolaryngology. There are many causes of epistaxis, but reports of epistaxis due to nasal foreign bodies like leeches are...
RATIONALE
Epistaxis is one of the common emergencies in otolaryngology. There are many causes of epistaxis, but reports of epistaxis due to nasal foreign bodies like leeches are rare.
PATIENT CONCERNS
A 55-year-old male presented with "repeated epistaxis for over 20 days." Nasal endoscopy revealed a live leech in the olfactory area of the left nostril.
DIAGNOSES
The patient was diagnosed with epistaxis caused by a live leech in the nasal cavity.
INTERVENTIONS
Under nasal endoscopy, the leech was grasped with a vascular clamp and removed from the nasal cavity. The leech measured 8 cm in length. Hemostasis was achieved using a gelatin sponge at the wound site, and the nasal cavity was packed with Vaseline gauze.
OUTCOMES
The live leech was removed via nasal endoscopy. Two days later, the Vaseline gauze packing was removed, and the patient experienced no further nasal bleeding.
CONCLUSION
Live leeches in the nasal cavity can cause epistaxis. Nasal endoscopic removal of the live leech is an effective treatment.
LESSON
There are many causes of epistaxis, which are nonspecific and prone to missed or incorrect diagnosis. In patients with a history of fieldwork or direct contact with leeches who present with recurrent nasal bleeding, the possibility of epistaxis caused by a live leech should be considered, and timely and effective treatment should be provided.
Topics: Animals; Humans; Male; Middle Aged; Endoscopy; Epistaxis; Leeches; Nasal Cavity; Nose; Petrolatum
PubMed: 38579026
DOI: 10.1097/MD.0000000000037720 -
JCO Global Oncology Mar 2024Increased automation has been identified as one approach to improving global cancer care. The Radiation Planning Assistant (RPA) is a web-based tool offering automated...
PURPOSE
Increased automation has been identified as one approach to improving global cancer care. The Radiation Planning Assistant (RPA) is a web-based tool offering automated radiotherapy (RT) contouring and planning to low-resource clinics. In this study, the RPA workflow and clinical acceptability were assessed by physicians around the world.
METHODS
The RPA output for 75 cases was reviewed by at least three physicians; 31 radiation oncologists at 16 institutions in six countries on five continents reviewed RPA contours and plans for clinical acceptability using a 5-point Likert scale.
RESULTS
For cervical cancer, RPA plans using bony landmarks were scored as usable as-is in 81% (with minor edits 93%); using soft tissue contours, plans were scored as usable as-is in 79% (with minor edits 96%). For postmastectomy breast cancer, RPA plans were scored as usable as-is in 44% (with minor edits 91%). For whole-brain treatment, RPA plans were scored as usable as-is in 67% (with minor edits 99%). For head/neck cancer, the normal tissue autocontours were acceptable as-is in 89% (with minor edits 97%). The clinical target volumes (CTVs) were acceptable as-is in 40% (with minor edits 93%). The volumetric-modulated arc therapy (VMAT) plans were acceptable as-is in 87% (with minor edits 96%). For cervical cancer, the normal tissue autocontours were acceptable as-is in 92% (with minor edits 99%). The CTVs for cervical cancer were scored as acceptable as-is in 83% (with minor edits 92%). The VMAT plans for cervical cancer were acceptable as-is in 99% (with minor edits 100%).
CONCLUSION
The RPA, a web-based tool designed to improve access to high-quality RT in low-resource settings, has high rates of clinical acceptability by practicing clinicians around the world. It has significant potential for successful implementation in low-resource clinics.
Topics: Female; Humans; Breast Neoplasms; Artificial Intelligence; Uterine Cervical Neoplasms; Radiotherapy Planning, Computer-Assisted; Mastectomy
PubMed: 38484191
DOI: 10.1200/GO.23.00376 -
Clinical and Translational Radiation... Mar 2024Consistent delineation of the breast conserving surgery (BCS) tumour bed (TB) for breast cancer remains a challenge for radiation oncologists. Accurate delineation...
INTRODUCTION
Consistent delineation of the breast conserving surgery (BCS) tumour bed (TB) for breast cancer remains a challenge for radiation oncologists. Accurate delineation allows for better local control and reduces toxicity when planning partial breast or TB boost radiation therapy (RT).
METHODS
In the operating theatre (OT) breast surgeons inserted stabilised hyaluronic acid (sHA) gel as small drops approximately one cm into the walls surrounding the resection cavity. Surgical feasibility was determined by the rate of successful sHA gel insertion procedure, the ease of insertion as rated by surgeons, the time required for insertion procedure, the quantity used, and any adverse events (AE) relating to sHA gel insertion.
RESULTS
Thirty-five patients were enrolled. All patients underwent sHA gel insertion successfully. The procedure added a median of 2.8 min to the OT time and was rated as 'easy' in 89 % of patients. There were no immediate AE in OT. Five (14 %) patients experienced a grade 2 or higher AE. Three of the five patients were prescribed oral antibiotics for breast infection. Two of the five patients experienced a grade 3 AE - haematoma which required evacuation in OT day 1 post-BCS, and infected seroma which required drainage and washout in OT 2 months post-BCS. All five patients recovered and underwent the planned adjuvant therapies for their BC. The AE data reflects common risks with standard BCS and are not clearly attributed to sHA gel insertion alone.
CONCLUSION
We show that sHA gel is surgically feasible as a marker to help define the TB cavity for post-BCS adjuvant MRI-based RT planning.
PubMed: 38406647
DOI: 10.1016/j.ctro.2024.100745