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JAMA Nov 2023Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute...
IMPORTANCE
Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute fibrinogen deficiency. Management is fibrinogen replacement with cryoprecipitate transfusions or fibrinogen concentrate, usually administered relatively late during hemorrhage.
OBJECTIVE
To assess whether survival could be improved by administering an early and empirical high dose of cryoprecipitate to all patients with trauma and bleeding that required activation of a major hemorrhage protocol.
DESIGN, SETTING, AND PARTICIPANTS
CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study. Patients were enrolled at 26 UK and US major trauma centers from August 2017 to November 2021. Eligible patients were injured adults requiring activation of the hospital's major hemorrhage protocol with evidence of active hemorrhage, systolic blood pressure less than 90 mm Hg at any time, and receiving at least 1 U of a blood component transfusion.
INTERVENTION
Patients were randomly assigned (in a 1:1 ratio) to receive standard care, which was the local major hemorrhage protocol (reviewed for guideline adherence), or cryoprecipitate, in which 3 pools of cryoprecipitate (6-g fibrinogen equivalent) were to be administered in addition to standard care within 90 minutes of randomization and 3 hours of injury.
MAIN OUTCOMES AND MEASURES
The primary outcome was all-cause mortality at 28 days in the intention-to-treat population.
RESULTS
Among 1604 eligible patients, 799 were randomized to the cryoprecipitate group and 805 to the standard care group. Missing primary outcome data occurred in 73 patients (principally due to withdrawal of consent) and 1531 (95%) were included in the primary analysis population. The median (IQR) age of participants was 39 (26-55) years, 1251 (79%) were men, median (IQR) Injury Severity Score was 29 (18-43), 36% had penetrating injury, and 33% had systolic blood pressure less than 90 mm Hg at hospital arrival. All-cause 28-day mortality in the intention-to-treat population was 26.1% in the standard care group vs 25.3% in the cryoprecipitate group (odds ratio, 0.96 [95% CI, 0.75-1.23]; P = .74). There was no difference in safety outcomes or incidence of thrombotic events in the standard care vs cryoprecipitate group (12.9% vs 12.7%).
CONCLUSIONS AND RELEVANCE
Among patients with trauma and bleeding who required activation of a major hemorrhage protocol, the addition of early and empirical high-dose cryoprecipitate to standard care did not improve all cause 28-day mortality.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04704869; ISRCTN Identifier: ISRCTN14998314.
Topics: Adult; Male; Humans; Middle Aged; Female; Hemorrhage; Fibrinogen; Blood Transfusion; Blood Component Transfusion; Wounds, Penetrating
PubMed: 37824155
DOI: 10.1001/jama.2023.21019 -
Indian Dermatology Online Journal 2023Leeches are hermaphroditic parasites of phylum Annelida and class Hirudinea. A minority of these are sanguinivorous and the cause of human morbidity. Historically,...
Leeches are hermaphroditic parasites of phylum Annelida and class Hirudinea. A minority of these are sanguinivorous and the cause of human morbidity. Historically, leeches have been used for medicinal purposes with the earliest recorded being 1500 BC. Medicinal leeches use their suction discs for locomotion, adhesion to the host, and, in the case of the anterior disc, also for blood ingestion. Dermoscopy is a new non-invasive tool that can help in the diagnosis of miscellaneous skin conditions. The new dermoscopic sign of leech bite i.e., the Mercedes Benz Logo sign which corresponds to the retractable tripartite jaw apparatus of the leech, can easily help in the quick diagnosis of the condition and referral of the patient for proper management without any delay.
PubMed: 37727570
DOI: 10.4103/idoj.idoj_414_22 -
Acta Chirurgica Belgica Dec 2023Dawali (varicose veins) is the disease of chronic dilation of veins. The veins of the legs become dilated and blue due to excessive accumulation of blood. This disease... (Review)
Review
INTRODUCTION
Dawali (varicose veins) is the disease of chronic dilation of veins. The veins of the legs become dilated and blue due to excessive accumulation of blood. This disease and the effort to identify and treat it has a very long history. The condition may have first been described in the Ebers Papyrus more than 3500 years ago. The present study deals with the turning points and progress of varicose vein surgery since ancient times, emphasizing the innovations of the scholars of the Islamic period.
METHODS
The present study is based on searching library documents and database data such as PubMed, Scopus, Science Direct, and search engines such as Google Scholar. In the end, the Prisma flow chart was drawn.
RESULTS
Besides diagnosing different varicose veins (legs, thighs, abdomen, uterus, and testes), the scholars of the Islamic period were well-versed in their prevention, etiology, and treatment. In treating varicose veins, these physicians used methods such as cleansing, phlebotomy, compression, leech therapy, and surgery, and some of them were the founders of new treatments.
CONCLUSION
The surgical treatment of varicose veins in the past was similar to modern surgical therapies. What distinguishes yesterday's varicose vein surgery from today's surgery is a more advanced tool. There is no denying the remarkable progress in using health principles, treatment techniques, and surgical instruments to facilitate surgery and reduce the disease's complications and recurrence. However, the treatment framework and foundation, such as phlebectomy and compression, were all invented and introduced in the distant past.
Topics: Female; Humans; Vascular Surgical Procedures; Varicose Veins; Leg; Treatment Outcome
PubMed: 37671628
DOI: 10.1080/00015458.2023.2254603 -
Journal of Ethnopharmacology Apr 2024Leech, as a traditional Chinese medicine for the treatment of blood circulation and blood stasis, was also widely used to cure pulmonary fibrosis in China. In clinical...
ETHNOPHARMACOLOGICAL RELEVANCE
Leech, as a traditional Chinese medicine for the treatment of blood circulation and blood stasis, was also widely used to cure pulmonary fibrosis in China. In clinical practice, some traditional Chinese medicine preparation such as Shui Zhi Xuan Bi Hua Xian Tang and Shui Zhi Tong Luo Capsule composed of leech, could improve the clinical symptoms and pulmonary function in patients with idiopathic pulmonary fibrosis (IPF). However, the material basis of the leech in the treatment of IPF were not yet clear.
AIM OF THE STUDY
Screen out the components of leech that have the anti-pulmonary fibrosis effects, and further explore the therapeutic mechanism of the active components.
MATERIALS AND METHODS
In this study, the different molecular weight components of leech extract samples were prepared using the semi-permeable membranes with different pore sizes. The therapeutic effects of the leech extract groups with molecular weight greater than 10 KDa (>10 KDa group), between 3 KDa and 10 KDa (3-10 KDa group), and less than 3 KDa (<3 KDa group) on pulmonary fibrosis were firstly investigated by cell proliferation and cytotoxicity assay (MTT), cell wound healing assay, immunofluorescence staining (IF) and Western blot (WB) assay through the TGF-β1-induced fibroblast cell model. Then bleomycin-induced pulmonary fibrosis (BML-induced PF) mouse model was constructed to investigate the pharmacological activities of the active component group of leech extract in vivo. Pathological changes of the mouse lung were observed by hematoxylin-eosin staining (H&E) and Masson's trichrome staining (Masson). The hydroxyproline (HYP) content of lung tissues was quantified by HYP detection kit. The levels of extracellular matrix-related fibronectin (FN) and collagen type Ⅰ (Collagen Ⅰ), pyruvate kinase M2 (PKM2) monomer and Smad7 protein were determined via WB method. PKM2 and Smad7 protein were further characterized by IF assays.
RESULTS
Using TGF-β1-induced HFL1 cell line as a PF cell model, the in vitro results demonstrated that the >10 KDa group could significantly inhibited the cell proliferation and migration, downregulated the expression level of cytoskeletal protein vimentin and α-smooth muscle actin (α-SMA), and reduced the deposition of FN and Collagen Ⅰ. In the BML-induced PF mouse model, the >10 KDa group significantly reduced the content of HYP, downregulated the expression levels of FN and Collagen Ⅰ in lung tissues, and delayed the pathological changes of lung tissue structure. The results of WB and IF assays further indicated that the >10 KDa group could up-regulate the expression level of PKM2 monomer and Smad7 protein in the cellular level, thereby delaying the progression of pulmonary fibrosis.
CONCLUSIONS
Our study revealed that the >10 KDa group was the main material basis of the leech extract that inhibited pulmonary fibrosis through TGF-β1/Smad3 signaling pathway.
Topics: Mice; Animals; Humans; Transforming Growth Factor beta1; Smad7 Protein; Idiopathic Pulmonary Fibrosis; Collagen Type I; Bleomycin; Disease Models, Animal; Signal Transduction
PubMed: 38228229
DOI: 10.1016/j.jep.2024.117737 -
JAMA Pediatrics Jul 2023The risk of serious long-term outcomes for infants born to individuals with opioid use disorder (OUD) is not fully characterized, nor is it well understood whether risks...
IMPORTANCE
The risk of serious long-term outcomes for infants born to individuals with opioid use disorder (OUD) is not fully characterized, nor is it well understood whether risks are modified by infant diagnosis of neonatal opioid withdrawal syndrome (NOWS).
OBJECTIVE
To characterize the risk of postneonatal infant mortality among infants with a NOWS diagnosis or born to individuals with OUD.
DESIGN, SETTING, AND PARTICIPANTS
The study team conducted a retrospective cohort study of 390 075 infants born from 2007 through 2018 to mothers who were enrolled in Tennessee Medicaid from 183 days prior to delivery through 28 days post partum (baseline). Maternal and infant baseline characteristics were measured using administrative claims and birth certificates, and infants were followed up from day 29 post partum through day 365 or death. Deaths were identified using linked death certificates through 2019. These data were analyzed from February 10, 2022, through March 3, 2023.
EXPOSURE
Infant exposures included birth to an individual with OUD or postnatal diagnosis of NOWS. The study team defined a pregnant individual's OUD status (maternal OUD) as having OUD diagnosis or a maintenance medication prescription fill during baseline; this study defined NOWS as having NOWS diagnosis up to day 28. Groups were categorized by exposures as maternal OUD with NOWS (OUD positive/NOWS positive), maternal OUD without NOWS (OUD positive/NOWS negative), no documented maternal OUD with NOWS (OUD negative/NOWS positive), and no documented maternal OUD or NOWS (OUD negative/NOWS negative, unexposed).
MAIN OUTCOME AND MEASURES
The outcome was postneonatal infant death, confirmed by death certificates. Cox proportional hazards models were used, adjusting for baseline maternal and infant characteristics, to estimate adjusted hazard ratios (aHRs) and 95% CIs for the association between maternal OUD or NOWS diagnosis with postneonatal death.
RESULTS
Pregnant individuals in the cohort had a mean (SD) age of 24.5 (5.2) years; 51% of infants were male. The study team observed 1317 postneonatal infant deaths and incidence rates of 3.47 (OUD negative/NOWS negative, 375 718), 8.41 (OUD positive/NOWS positive, 4922); 8.95 (OUD positive/NOWS negative, 7196), and 9.25 (OUD negative/NOWS positive, 2239) per 1000 person-years. After adjustment, the risk of postneonatal death was elevated for all groups, relative to the unexposed: OUD positive/NOWS positive (aHR, 1.54; 95% CI, 1.07-2.21), OUD positive/NOWS negative (aHR, 1.62; 95% CI, 1.21-2.17), and OUD negative/NOWS positive (aHR, 1.64; 95% CI, 1.02-2.65).
CONCLUSIONS AND RELEVANCE
Infants born to individuals with OUD or with a NOWS diagnosis had an increased risk of postneonatal infant mortality. Future work is necessary to create and evaluate supportive interventions for individuals with OUD during and after pregnancy to reduce adverse outcomes.
Topics: Infant; Infant, Newborn; Pregnancy; Female; Male; Humans; Young Adult; Adult; Retrospective Studies; Infant Mortality; Opioid-Related Disorders; Mothers; Neonatal Abstinence Syndrome; Analgesics, Opioid
PubMed: 37155175
DOI: 10.1001/jamapediatrics.2023.1047 -
International Journal of Molecular... Jul 2023When attacks its prey, the prey bleeds profusely but feels little pain. We and other research teams have identified several anticoagulant molecules in the saliva of ,...
When attacks its prey, the prey bleeds profusely but feels little pain. We and other research teams have identified several anticoagulant molecules in the saliva of , but the substance that produces the paralyzing effect in is not known. In this study, we successfully isolated, purified, and identified a serine protease inhibitor containing an antistasin-like domain from the salivary secretions of . This peptide (named poeciguamerin) significantly inhibited elastase activity and slightly inhibited FXIIa and kallikrein activity, but had no effect on FXa, trypsin, or thrombin activity. Furthermore, poeciguamerin exhibited analgesic activity in the foot-licking and tail-withdrawal mouse models and anticoagulant activity in the FeCl-induced carotid artery thrombosis mouse model. In this study, poeciguamerin was found to be a promising elastase inhibitor with potent analgesic and antithrombotic activity for the inhibition of pain and thrombosis after surgery or in inflammatory conditions.
Topics: Animals; Mice; Leeches; Serine Proteinase Inhibitors; Serpins; Anticoagulants; Thrombosis; Pancreatic Elastase; Analgesics; Pain
PubMed: 37446275
DOI: 10.3390/ijms241311097 -
Matrix Biology : Journal of the... Nov 2023Fibrosis is associated with dramatic changes in extracellular matrix (ECM) architecture of unknown etiology. Here we exploit keloid scars as a paradigm to understand...
Fibrosis is associated with dramatic changes in extracellular matrix (ECM) architecture of unknown etiology. Here we exploit keloid scars as a paradigm to understand fibrotic ECM organization. We reveal that keloid patient fibroblasts uniquely produce a globally aligned ECM network in 2-D culture as observed in scar tissue. ECM anisotropy develops after rapid initiation of a fibroblast supracellular actin network, suggesting that cell alignment initiates ECM patterning. Keloid fibroblasts produce elevated levels of IL-6, and autocrine IL-6 production is both necessary and sufficient to induce cell and ECM alignment, as evidenced by ligand stimulation of normal dermal fibroblasts and treatment of keloid fibroblasts with the function blocking IL-6 receptor monoclonal antibody, tocilizumab. Downstream of IL-6, supracellular organization of keloid fibroblasts is controlled by activation of cell-cell adhesion. Adhesion formation inhibits contact-induced cellular overlap leading to nematic organization of cells and an alignment of focal adhesions. Keloid fibroblasts placed on isotropic ECM align the pre-existing matrix, suggesting that focal adhesion alignment leads to active anisotropic remodeling. These results show that IL-6-induced fibroblast cooperativity can control the development of a nematic ECM, highlighting both IL-6 signaling and cell-cell adhesions as potential therapeutic targets to inhibit this common feature of fibrosis.
Topics: Humans; Keloid; Interleukin-6; Anisotropy; Cells, Cultured; Extracellular Matrix; Fibroblasts
PubMed: 37660739
DOI: 10.1016/j.matbio.2023.08.004 -
Journal of Medical Imaging and... Apr 2024Advanced practitioners are healthcare professionals that are highly skilled with a particular area of expertise. These roles have been successfully implemented in many... (Review)
Review
Advanced practitioners are healthcare professionals that are highly skilled with a particular area of expertise. These roles have been successfully implemented in many healthcare settings, improving efficiency of the service, as well as enhancing the standard of care received by patients. Although advanced practice roles have been implemented in some radiation therapy departments, their implementation have yet to be facilitated in the majority of countries. The purpose of this review is to scope the literature available regarding established advanced practice roles in radiation therapy. The PRISMA strategy for the identification of relevant literature was adhered to. Two data bases, EMBASE and PubMed, were searched using combinations of the key words 'Advanced', 'Practice', 'APRT', 'Radiation', 'Therapy' and 'Radiotherapy'. Exclusion criteria were applied, and citation lists were also screened for additional relevant sources, including grey literature sources. A total of 35 relevant sources were identified that discussed advanced practice radiation therapy roles in the United Kingdom, Singapore, Canada, Australia and the USA. Means of role establishment and scope of practice were defined, and a number of advantages and challenges for advanced practice radiation therapist roles were identified. There are many benefits of implementing advanced practice roles in radiation therapy departments. Though the implementation of these roles can be challenging, the existing evidence indicates that it would be beneficial for the patient, the radiation therapist and the department as a whole. A more systematic approach, including reporting of quantitative outcomes may assist in the more widespread implementation of these roles.
Topics: Humans; Radiotherapy; Radiation Oncology
PubMed: 38450863
DOI: 10.1111/1754-9485.13634 -
Therapeutic Advances in Cardiovascular... 2024Vasospastic angina (VSA) refers to chest pain experienced as a consequence of myocardial ischaemia caused by epicardial coronary spasm, a sudden narrowing of the vessels... (Review)
Review
Vasospastic angina (VSA) refers to chest pain experienced as a consequence of myocardial ischaemia caused by epicardial coronary spasm, a sudden narrowing of the vessels responsible for an inadequate supply of blood and oxygen. Coronary artery spasm is a heterogeneous phenomenon that can occur in patients with non-obstructive coronary arteries and obstructive coronary artery disease, with transient spasm causing chest pain and persistent spasm potentially leading to acute myocardial infarction (MI). VSA was originally described as Prinzmetal angina or variant angina, classically presenting at rest, unlike most cases of angina (though in some patients, vasospasm may be triggered by exertion, emotional, mental or physical stress), and associated with transient electrocardiographic changes (transient ST-segment elevation, depression and/or T-wave changes). Ischaemia with non-obstructive coronary arteries (INOCA) is not a benign condition, as patients are at elevated risk of cardiovascular events including acute coronary syndrome, hospitalization due to heart failure, stroke and repeat cardiovascular procedures. INOCA patients also experience impaired quality of life and associated increased healthcare costs. VSA, an endotype of INOCA, is associated with major adverse events, including sudden cardiac death, acute MI and syncope, necessitating the study of the most effective treatment options currently available. The present literature review aims to summarize current data relating to the diagnosis and management of VSA and provide details on the sequence that treatment should follow.
Topics: Humans; Angina Pectoris, Variant; Coronary Vasospasm; Quality of Life; Coronary Angiography; Coronary Artery Disease; Myocardial Infarction; Chest Pain; Spasm
PubMed: 38343041
DOI: 10.1177/17539447241230400 -
JAMA Mar 2024Emtricitabine and tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP) is highly effective in cisgender men who have sex with men (MSM) when...
IMPORTANCE
Emtricitabine and tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP) is highly effective in cisgender men who have sex with men (MSM) when adherence is high (>4 doses/week). Real-world effectiveness and adherence with F/TDF for PrEP in cisgender women is less well characterized.
OBJECTIVE
To characterize the effectiveness of F/TDF for PrEP and its relationship with adherence in cisgender women.
DESIGN, SETTING, AND PARTICIPANTS
Data were pooled from 11 F/TDF PrEP postapproval studies conducted in 6 countries that included 6296 cisgender women aged 15 to 69 years conducted from 2012 to 2020. HIV incidence was evaluated according to adherence level measured objectively (tenofovir diphosphate concentration in dried blood spots or tenofovir concentration in plasma; n = 288) and subjectively (electronic pill cap monitoring, pill counts, self-report, and study-reported adherence scale; n = 2954) using group-based trajectory modeling.
EXPOSURES
F/TDF prescribed orally once a day. HIV incidence was analyzed in subgroups based on adherence trajectory.
MAIN OUTCOMES AND MEASURES
HIV incidence.
RESULTS
Of the 6296 participants, 46% were from Kenya, 28% were from South Africa, 21% were from India, 2.9% were from Uganda, 1.6% were from Botswana, and 0.8% were from the US. The mean (SD) age at PrEP initiation across all studies was 25 (7) years, with 61% of participants being younger than 25 years. The overall HIV incidence was 0.72 per 100 person-years (95% CI, 0.51-1.01; 32 incident HIV diagnoses among 6296 participants). Four distinct groups of adherence trajectories were identified: consistently daily (7 doses/week), consistently high (4-6 doses/week), high but declining (from a mean of 4-6 doses/week and then declining), and consistently low (less than 2 doses/week). None of the 498 women with consistently daily adherence acquired HIV. Only 1 of the 658 women with consistently high adherence acquired HIV (incidence rate, 0.13/100 person-years [95% CI, 0.02-0.92]). The incidence rate was 0.49 per 100 person-years (95% CI, 0.22-1.08) in the high but declining adherence group (n = 1166) and 1.27 per 100 person-years (95% CI, 0.53-3.04) in the consistently low adherence group (n = 632).
CONCLUSIONS AND RELEVANCE
In a pooled analysis of 11 postapproval studies of F/TDF for PrEP among cisgender women, overall HIV incidence was 0.72 per 100 person-years; individuals with consistently daily or consistently high adherence (4-6 doses/week) to PrEP experienced very low HIV incidence.
Topics: Male; Humans; Female; Tenofovir; Emtricitabine; Homosexuality, Male; Anti-HIV Agents; HIV Infections; Sexual and Gender Minorities; Counseling; Pre-Exposure Prophylaxis
PubMed: 38427359
DOI: 10.1001/jama.2024.0464