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The American Journal of Chinese Medicine Jun 2024The use of medicinal leeches in clinical therapy has been employed for a long time, as it was originally recognized for exerting antithrombin effects. These effects were...
The use of medicinal leeches in clinical therapy has been employed for a long time, as it was originally recognized for exerting antithrombin effects. These effects were due to the ability of the leech to continuously suck blood while attached to human skin. According to , leeches used in traditional Chinese medicine mainly consist of Whitman, Whitman, and , but the latter two species are relatively scarce. The main constituents of leeches are protein and peptide macromolecules. They can be categorized into two categories based on their pharmacological effects. One group consists of active ingredients that directly target the coagulation system, such as hirudin, heparin, and histamine, which are widely known. The other group comprises protease inhibitor components like Decorsin and Hementin. Among these, hirudin secreted by the salivary glands of the leech is the most potent thrombin inhibitor and served as the sole remedy for preventing blood clotting until the discovery of heparin. Additionally, leeches play a significant role in various traditional Chinese medicine formulations. In recent decades, medicinal leeches have been applied in fields including anti-inflammatory treatment, cardiovascular disease management, antitumor treatment, and many other medical conditions. In this review, we present a comprehensive overview of the historical journey and medicinal applications of leeches in various medical conditions, emphasizing their pharmaceutical significance within traditional Chinese medicine. This review offers valuable insights for exploring additional therapeutic opportunities involving the use of leeches in various diseases and elucidating their underlying mechanisms for future research.
PubMed: 38879745
DOI: 10.1142/S0192415X24500423 -
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 -
Journal of the American Chemical Society Jun 2024Covalent organic frameworks (COFs) have been explored for photodynamic therapy (PDT) of cancer, but their antitumor efficacy is limited by excited state quenching and...
Covalent organic frameworks (COFs) have been explored for photodynamic therapy (PDT) of cancer, but their antitumor efficacy is limited by excited state quenching and low reactive oxygen species generation efficiency. Herein, we report a simultaneous protonation and metalation strategy to significantly enhance the PDT efficacy of a nanoscale two-dimensional imine-linked porphyrin-COF. The neutral and unmetalated porphyrin-COF (Ptp) and the protonated and metalated porphyrin-COF (Ptp-Fe) were synthesized via imine condensation between 5,10,15,20-tetrakis(4-aminophenyl)porphyrin and terephthalaldehyde in the absence and presence of ferric chloride, respectively. The presence of ferric chloride generated both doubly protonated and Fe-coordinated porphyrin units, which red-shifted and increased the Q-band absorption and disrupted exciton migration to prevent excited state quenching, respectively. Under light irradiation, rapid energy transfer from protonated porphyrins to Fe-coordinated porphyrins in Ptp-Fe enabled O and hydroxyl radical generation via type II and type I PDT processes. Ptp-Fe also catalyzed the conversion of hydrogen peroxide to hydroxy radical through a photoenhanced Fenton-like reaction under slightly acidic conditions and light illumination. As a result, Ptp-Fe-mediated PDT exhibited much higher cytotoxicity than Ptp-mediated PDT on CT26 and 4T1 cancer cells. Ptp-Fe-mediated PDT afforded potent antitumor efficacy in subcutaneous CT26 murine colon cancer and orthotopic 4T1 murine triple-negative breast tumors and prevented metastasis of 4T1 breast cancer to the lungs. This work underscores the role of fine-tuning the molecular structures of COFs in significantly enhancing their PDT efficacy.
PubMed: 38837955
DOI: 10.1021/jacs.4c03519 -
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 -
Neuromodulation : Journal of the... Jun 2024High-frequency spinal cord stimulation (10-kHz SCS) has been shown to be an effective treatment for refractory low back pain and neck pain with and without limb pain in...
OBJECTIVES
High-frequency spinal cord stimulation (10-kHz SCS) has been shown to be an effective treatment for refractory low back pain and neck pain with and without limb pain in clinical trial and real-world studies. However, limited information is available in the literature on the type and frequency of programming parameters required to optimize pain relief.
MATERIALS AND METHODS
Retrospective trial and postimplant clinical and system device data were analyzed from consecutive patients with neck pain and low back pain, with and without limb pain, from a single clinical site, including both thoracic and cervical lead placement. Best bipole, stimulation parameters, and outcomes, including pain relief, change in opioid medication use, sleep, and daily function, were analyzed.
RESULTS
Of the 92 patients in the trial, 70 received a permanent implant. Of these, the mean duration of follow-up was 1.8 ± 1.3 years. Pain relief of ≥50% at the last follow-up was achieved by 64% of patients implanted; in addition, 65% reduced their opioid medication use; 65% reported improved sleep, and 71% reported improved function. There was some consistency between the "best" bipole at trial and permanent implant, with 82% of patients within one bipole location, including 54% of permanent implants who were using the same best bipole as at trial. After permanent implant, device reprogramming was minimal, with ≤one reprogramming change per patient per quarter required to maintain pain outcomes.
CONCLUSIONS
In the study, 10-kHz SCS was an effective therapy for treating chronic pain, whereby a high responder rate (≥50% pain relief) was achieved with short time to pain relief in trial and maintained with limited device programming after permanent implant. The data presented here provide insight into the programming required during the trial and implant stages to obtain and maintain therapeutic efficacy.
PubMed: 38829295
DOI: 10.1016/j.neurom.2024.04.005 -
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 -
Leech Therapy for Venous Congestion After Compartment Syndrome in a Patient With Systemic Sclerosis.The Journal of Rheumatology May 2024Fasciotomy is the definitive treatment for most cases of compartment syndrome. However, this surgical intervention does not come without risk.
Fasciotomy is the definitive treatment for most cases of compartment syndrome. However, this surgical intervention does not come without risk.
PubMed: 38749566
DOI: 10.3899/jrheum.2024-0134 -
Journal of Ethnopharmacology Sep 2024Chromolaenaodorata (L.) R.M. King & H. Rob, a perennial herb, has been traditionally utilized as a herbal remedy for treating leech bites, soft tissue wounds, burn...
Evaluation of hemostatic, anti-inflammatory, wound healing, skin irritation and allergy, and antimicrobial properties of active fraction from the ethanol extract of Chromolaena odorata (L.) R.M. King & H. Rob.
ETHNOPHARMACOLOGICAL RELEVANCE
Chromolaenaodorata (L.) R.M. King & H. Rob, a perennial herb, has been traditionally utilized as a herbal remedy for treating leech bites, soft tissue wounds, burn wounds, skin infections, and dento-alveolitis in tropical and subtropical regions.
AIM OF THE STUDY
The present study was to analyze the active fraction of C. odorata ethanol extract and investigate its hemostatic, anti-inflammatory, wound healing, and antimicrobial properties. Additionally, the safety of the active fraction as an external preparation was assessed through skin irritation and allergy tests.
MATERIALS AND METHODS
The leaves and stems of C. odorata were initially extracted with ethanol, followed by purification through AB-8 macroporous adsorption resin column chromatography to yield different fractions. These fractions were then screened for hemostatic activity in mice and rabbits to identify the active fraction. Subsequently, the hemostatic effect of the active fraction was assessed through the bleeding time of the rabbit ear artery in vivo and the coagulant time of rabbit blood in vitro. The anti-inflammatory activity of the active fraction was tested on mice ear edema induced by xylene and rat paw edema induced by carrageenin. Furthermore, the active fraction's promotion effect on wound healing was evaluated using a rat skin injury model, and skin safety tests were conducted on rabbits and guinea pigs. Lastly, antimicrobial activities against two Gram-positive bacteria (G, Staphylococcus aureus and S. epidermidis) and three Gram-negative bacteria (G, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were determined using the plate dilution method.
RESULTS
The ethanol extract of C. odorata leaves and stems was fractionated into 30%, 60%, and 90% ethanol eluate fractions. These fractions demonstrated hemostatic activity, with the 30% ethanol eluate fraction (30% EEF) showing the strongest effect, significantly reducing bleeding time (P < 0.05). A concentration of 1.0 g/mL of the 30% EEF accelerated cutaneous wound healing in rats on the 3rd, 6th, and 9th day post-operation, with the healing effect increasing over time. No irritation or allergy reactions were observed in rabbits and guinea pigs exposed to the 30% EEF. Additionally, the 30% EEF exhibited mild inhibitory effect on mice ear and rat paw edema, as well as antimicrobial activity against tested bacteria, with varying minimal inhibitory concentration (MIC) values.
CONCLUSIONS
The 30% EEF demonstrated a clear hemostatic effect on rabbit bleeding time, a slight inhibitory effect on mice ear edema and rat paw edema, significant wound healing activity in rats, and no observed irritation or allergic reactions. Antibacterial activity was observed against certain clinically isolated bacteria, particularly the G bacteria. This study lays the groundwork for the potential development and application of C. odorata in wound treatment.
Topics: Animals; Rabbits; Wound Healing; Plant Extracts; Anti-Inflammatory Agents; Mice; Male; Hemostatics; Ethanol; Chromolaena; Edema; Rats; Skin; Female; Anti-Infective Agents; Plant Leaves; Hypersensitivity; Xylenes; Plant Stems
PubMed: 38740109
DOI: 10.1016/j.jep.2024.118330 -
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