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JAMA Aug 2023Current guidelines for treating small- to medium-sized vestibular schwannoma recommend either upfront radiosurgery or waiting to treat until tumor growth has been... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Current guidelines for treating small- to medium-sized vestibular schwannoma recommend either upfront radiosurgery or waiting to treat until tumor growth has been detected radiographically.
OBJECTIVE
To determine whether upfront radiosurgery provides superior tumor volume reduction to a wait-and-scan approach for small- to medium-sized vestibular schwannoma.
DESIGN, SETTING, AND PARTICIPANTS
Randomized clinical trial of 100 patients with a newly diagnosed (<6 months) unilateral vestibular schwannoma and a maximal tumor diameter of less than 2 cm in the cerebellopontine angle as measured on magnetic resonance imaging. Participants were enrolled at the Norwegian National Unit for Vestibular Schwannoma from October 28, 2014, through October 3, 2017; 4-year follow-up ended on October 20, 2021.
INTERVENTIONS
Participants were randomized to receive either upfront radiosurgery (n = 50) or to undergo a wait-and-scan protocol, for which treatment was given only upon radiographically documented tumor growth (n = 50). Participants underwent 5 annual study visits consisting of clinical assessment, radiological examination, audiovestibular tests, and questionnaires.
MAIN OUTCOMES AND MEASURES
The primary outcome was the ratio between tumor volume at the trial end at 4 years and baseline (V4:V0). There were 26 prespecified secondary outcomes, including patient-reported symptoms, clinical examinations, audiovestibular tests, and quality-of-life outcomes. Safety outcomes were the risk of salvage microsurgery and radiation-associated complications.
RESULTS
Of the 100 randomized patients, 98 completed the trial and were included in the primary analysis (mean age, 54 years; 42% female). In the upfront radiosurgery group, 1 participant (2%) received repeated radiosurgery upon tumor growth, 2 (4%) needed salvage microsurgery, and 45 (94%) had no additional treatment. In the wait-and-scan group, 21 patients (42%) received radiosurgery upon tumor growth, 1 (2%) underwent salvage microsurgery, and 28 (56%) remained untreated. For the primary outcome of the ratio of tumor volume at the trial end to baseline, the geometric mean V4:V0 was 0.87 (95% CI, 0.66-1.15) in the upfront radiosurgery group and 1.51 (95% CI, 1.23-1.84) in the wait-and-scan group, showing a significantly greater tumor volume reduction in patients treated with upfront radiosurgery (wait-and-scan to upfront radiosurgery ratio, 1.73; 95% CI, 1.23-2.44; P = .002). Of 26 secondary outcomes, 25 showed no significant difference. No radiation-associated complications were observed.
CONCLUSION AND RELEVANCE
Among patients with newly diagnosed small- and medium-sized vestibular schwannoma, upfront radiosurgery demonstrated a significantly greater tumor volume reduction at 4 years than a wait-and-scan approach with treatment upon tumor growth. These findings may help inform treatment decisions for patients with vestibular schwannoma, and further investigation of long-term clinical outcomes is needed.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02249572.
Topics: Female; Humans; Male; Middle Aged; Neuroma, Acoustic; Radiosurgery; Retrospective Studies; Treatment Outcome; Watchful Waiting; Magnetic Resonance Imaging; Cerebellopontine Angle; Salvage Therapy; Microsurgery
PubMed: 37526718
DOI: 10.1001/jama.2023.12222 -
BMC Public Health Aug 2023Even though cadmium (Cd) exposure and cellular senescence (telomere length) have been linked in previous studies, composite molecular aging biomarkers are more...
INTRODUCTION
Even though cadmium (Cd) exposure and cellular senescence (telomere length) have been linked in previous studies, composite molecular aging biomarkers are more significant and reliable factors to consider when examining the connection between metal exposure and health outcomes. The purpose of this research was to assess the association between urinary cadmium (U-Cd) and whole-body aging (phenotypic age).
METHODS
Phenotypic age was calculated from chronological age and 9 molecular biomarkers. Multivariate linear regression models, subgroup analysis, and smoothing curve fitting were used to explore the linear and nonlinear relationship between U-Cd and phenotypic age. Mediation analysis was performed to explore the mediating effect of U-Cd on the association between smoking and phenotypic age.
RESULTS
This study included 10,083 participants with a mean chronological age and a mean phenotypic age of 42.24 years and 42.34 years, respectively. In the fully adjusted model, there was a positive relationship between U-Cd and phenotypic age [2.13 years per 1 ng/g U-Cd, (1.67, 2.58)]. This association differed by sex, age, and smoking subgroups (P for interaction < 0.05). U-Cd mediated a positive association between serum cotinine and phenotypic age, mediating a proportion of 23.2%.
CONCLUSIONS
Our results suggest that high levels of Cd exposure are associated with whole-body aging.
Topics: Adult; Humans; Aging; Cadmium; Cotinine; Mediation Analysis; Nutrition Surveys; Male; Female
PubMed: 37653508
DOI: 10.1186/s12889-023-16643-2 -
JAMA Aug 2023Prior trials of extracranial-intracranial (EC-IC) bypass surgery showed no benefit for stroke prevention in patients with atherosclerotic occlusion of the internal... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Prior trials of extracranial-intracranial (EC-IC) bypass surgery showed no benefit for stroke prevention in patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), but there have been subsequent improvements in surgical techniques and patient selection.
OBJECTIVE
To evaluate EC-IC bypass surgery in symptomatic patients with atherosclerotic occlusion of the ICA or MCA, using refined patient and operator selection.
DESIGN, SETTING, AND PARTICIPANTS
This was a randomized, open-label, outcome assessor-blinded trial conducted at 13 centers in China. A total of 324 patients with ICA or MCA occlusion with transient ischemic attack or nondisabling ischemic stroke attributed to hemodynamic insufficiency based on computed tomography perfusion imaging were recruited between June 2013 and March 2018 (final follow-up: March 18, 2020).
INTERVENTIONS
EC-IC bypass surgery plus medical therapy (surgical group; n = 161) or medical therapy alone (medical group; n = 163). Medical therapy included antiplatelet therapy and stroke risk factor control.
MAIN OUTCOMES AND MEASURES
The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. There were 9 secondary outcomes, including any stroke or death within 2 years and fatal stroke within 2 years.
RESULTS
Among 330 patients who were enrolled, 324 patients were confirmed eligible (median age, 52.7 years; 257 men [79.3%]) and 309 (95.4%) completed the trial. For the surgical group vs medical group, no significant difference was found for the composite primary outcome (8.6% [13/151] vs 12.3% [19/155]; incidence difference, -3.6% [95% CI, -10.1% to 2.9%]; hazard ratio [HR], 0.71 [95% CI, 0.33-1.54]; P = .39). The 30-day risk of stroke or death was 6.2% (10/161) in the surgical group and 1.8% (3/163) in the medical group, and the risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2.0% (3/151) and 10.3% (16/155), respectively. Of the 9 prespecified secondary end points, none showed a significant difference including any stroke or death within 2 years (9.9% [15/152] vs 15.3% [24/157]; incidence difference, -5.4% [95% CI, -12.5% to 1.7%]; HR, 0.69 [95% CI, 0.34-1.39]; P = .30) and fatal stroke within 2 years (2.0% [3/150] vs 0% [0/153]; incidence difference, 1.9% [95% CI, -0.2% to 4.0%]; P = .08).
CONCLUSIONS AND RELEVANCE
Among patients with symptomatic ICA or MCA occlusion and hemodynamic insufficiency, the addition of bypass surgery to medical therapy did not significantly change the risk of the composite outcome of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01758614.
Topics: Female; Humans; Male; Middle Aged; Arteriosclerosis; Carotid Artery Diseases; Carotid Artery, Internal; Cerebral Revascularization; Infarction, Middle Cerebral Artery; Intracranial Arteriosclerosis; Ischemic Attack, Transient; Ischemic Stroke; Middle Cerebral Artery; Perfusion Imaging; Single-Blind Method; Stroke; Tomography, Emission-Computed; Platelet Aggregation Inhibitors; Combined Modality Therapy
PubMed: 37606672
DOI: 10.1001/jama.2023.13390 -
Sensors (Basel, Switzerland) Oct 2023Microsurgical techniques have been widely utilized in various surgical specialties, such as ophthalmology, neurosurgery, and otolaryngology, which require intricate and... (Review)
Review
Microsurgical techniques have been widely utilized in various surgical specialties, such as ophthalmology, neurosurgery, and otolaryngology, which require intricate and precise surgical tool manipulation on a small scale. In microsurgery, operations on delicate vessels or tissues require high standards in surgeons' skills. This exceptionally high requirement in skills leads to a steep learning curve and lengthy training before the surgeons can perform microsurgical procedures with quality outcomes. The microsurgery robot (MSR), which can improve surgeons' operation skills through various functions, has received extensive research attention in the past three decades. There have been many review papers summarizing the research on MSR for specific surgical specialties. However, an in-depth review of the relevant technologies used in MSR systems is limited in the literature. This review details the technical challenges in microsurgery, and systematically summarizes the key technologies in MSR with a developmental perspective from the basic structural mechanism design, to the perception and human-machine interaction methods, and further to the ability in achieving a certain level of autonomy. By presenting and comparing the methods and technologies in this cutting-edge research, this paper aims to provide readers with a comprehensive understanding of the current state of MSR research and identify potential directions for future development in MSR.
Topics: Humans; Robotics; Microsurgery; Neurosurgical Procedures; Neurosurgery; Clinical Competence
PubMed: 37896597
DOI: 10.3390/s23208503 -
British Journal of Hospital Medicine... Oct 2023Supermicrosurgery was popularised in 1997 and is defined as a technique of microvascular anastomosis for single nerve fascicles and vessels 0.3-0.8 mm in diameter. It... (Review)
Review
Supermicrosurgery was popularised in 1997 and is defined as a technique of microvascular anastomosis for single nerve fascicles and vessels 0.3-0.8 mm in diameter. It requires the use of powerful microscopes, ultradelicate microsurgical instruments and specialist dyes. The development of supermicrosurgery has vastly improved the ability of microsurgeons to create true perforator flaps with minimal donor site morbidity for reconstructive surgery and improved the precision of additional microsurgical techniques. This review outlines the origins and history of supermicrosurgery, its current applications in reconstructive surgery (including fingertip reconstructions, true perforator flap surgery, nerve flaps and lymphoedema surgery), supermicrosurgery training and future directions for the field.
Topics: Humans; Plastic Surgery Procedures; Surgical Flaps; Anastomosis, Surgical; Lymphedema
PubMed: 37906072
DOI: 10.12968/hmed.2022.0482 -
Journal of Xenobiotics Sep 2023Dyes, such as indigo carmine, have become indispensable to modern life, being widely used in the food, textile, pharmaceutical, medicine, and cosmetic industry. Although... (Review)
Review
Dyes, such as indigo carmine, have become indispensable to modern life, being widely used in the food, textile, pharmaceutical, medicine, and cosmetic industry. Although indigo carmine is considered toxic and has many adverse effects, it is found in many foods, and the maximum permitted level is 500 mg/kg. Indigo carmine is one of the most used dyes in the textile industry, especially for dyeing denim, and it is also used in medicine due to its impressive applicability in diagnostic methods and surgical procedures, such as in gynecological and urological surgeries and microsurgery. It is reported that indigo carmine is toxic for humans and can cause various pathologies, such as hypertension, hypotension, skin irritations, or gastrointestinal disorders. In this review, we discuss the structure and properties of indigo carmine; its use in various industries and medicine; the adverse effects of its ingestion, injection, or skin contact; the effects on environmental pollution; and its toxicity testing. For this review, 147 studies were considered relevant. Most of the cited articles were those about environmental pollution with indigo carmine (51), uses of indigo carmine in medicine (45), and indigo carmine as a food additive (17).
PubMed: 37754845
DOI: 10.3390/jox13030033 -
Journal of Nanobiotechnology Sep 2023This study investigated whether exosomes from LPS pretreated bone marrow mesenchymal stem cells (LPS pre-MSCs) could prolong skin graft survival.
OBJECTIVES
This study investigated whether exosomes from LPS pretreated bone marrow mesenchymal stem cells (LPS pre-MSCs) could prolong skin graft survival.
METHODS
The exosomes were isolated from the supernatant of MSCs pretreated with LPS. LPS pre-Exo and rapamycin were injected via the tail vein into C57BL/6 mice allografted with BALB/c skin; graft survival was observed and evaluated. The accumulation and polarization of macrophages were examined by immunohistochemistry. The differentiation of macrophages in the spleen was analyzed by flow cytometry. For in vitro, an inflammatory model was established. Specifically, bone marrow-derived macrophages (BMDMs) were isolated and cultured with LPS (100 ng/ml) for 3 h, and were further treated with LPS pre-Exo for 24 h or 48 h. The molecular signaling pathway responsible for modulating inflammation was examined by Western blotting. The expressions of downstream inflammatory cytokines were determined by Elisa, and the polarization of macrophages was analyzed by flow cytometry.
RESULTS
LPS pre-Exo could better ablate inflammation compared to untreated MSC-derived exosomes (BM-Exo). These loaded factors inhibited the expressions of inflammatory factors via a negative feedback mechanism. In vivo, LPS pre-Exo significantly attenuated inflammatory infiltration, thus improving the survival of allogeneic skin graft. Flow cytometric analysis of BMDMs showed that LPS pre-Exo were involved in the regulation of macrophage polarization and immune homeostasis during inflammation. Further investigation revealed that the NF-κB/NLRP3/procaspase-1/IL-1β signaling pathway played a key role in LPS pre-Exo-mediated regulation of macrophage polarization. Inhibiting NF-κB in BMDMs could abolish the LPS-induced activation of inflammatory pathways and the polarization of M1 macrophages while increasing the proportion of M2 cells.
CONCLUSION
LPS pre-Exo are able to switch the polarization of macrophages and enhance the resolution of inflammation. This type of exosomes provides an improved immunotherapeutic potential in prolonging graft survival.
Topics: Mice; Animals; Mice, Inbred C57BL; NF-kappa B; Lipopolysaccharides; NLR Family, Pyrin Domain-Containing 3 Protein; Exosomes; Bone Marrow; Signal Transduction; Allografts
PubMed: 37716974
DOI: 10.1186/s12951-023-02087-8 -
International Journal of Surgery... Feb 2024During laparoscopic surgery, the operating surgeon grasps sections of the gastrointestinal tract (GIT), including delicate structures, with long (270 mm) 5 mm diameter...
BACKGROUND
During laparoscopic surgery, the operating surgeon grasps sections of the gastrointestinal tract (GIT), including delicate structures, with long (270 mm) 5 mm diameter graspers. These grasping instruments increase the risk of iatrogenic damage due to crushing of the grasped tissue. This risk is increased significantly by diseases such as bacterial peritonitis and inflammatory bowel disease and reduced but not abolished by using parallel-closing laparoscopic instruments. This study describes the design and laboratory testing of fully developed and tested smart graspers capable of reducing the grasping force used for inflamed tissues and hollow viscera.
MATERIALS AND METHODS
In an ISO 13485-certified mechanical laboratory and CAD machine workshop, the authors have designed, developed, and evaluated a smart gasper capable of exerting a preselected uniform grasping force on the gastrointestinal tract and other structures/ tissues, through a mechanism incorporated in the handle of the instrument. This enables the control and graded reduction of the grasping force by the incorporation of a compression spring. The authors named the new instrument the force-adjustable parallel-occlusion grasper (FA-POG) because, in addition to applying a uniform force on the grasped bowel/tissue, it also enables the surgeon to select the force before grasping, depending on its physical condition, and pathological state.
RESULTS
FA-POG differs from traditional pinch-occlusion grasper in two respects: it exerts a uniform force on the grasped tissue/bowel and enables the operating surgeon to select and apply a predetermined uniform grasping force, ranging from 1 to 5 N, depending on the pathological condition of the bowel/structure. The ISO 13485-certified and fully developed prototype has been subjected to various grasping in-vitro tests using freshly harvested porcine small-bowel segments obtained from a local abattoir, using Instron tensiometry.
CONCLUSIONS
The authors designed and α/β tested a parallel-occlusion gasper that enables the operating surgeon to select the force before grasping. This grasper design consists of end-effectors jaws with a 4-bar linkage mechanism for wide, uniform parallel-occlusion force, surpassing traditional scissor-type laparoscopic graspers. It incorporates a force-level controller knob, based on a spring-loaded mechanism, enabling surgeon-preselected grip force to prevent excessive grasping. The authors validated the design experimentally using porcine small-bowel segments, optimizing teeth for maximum grip friction to minimize slippage.
Topics: Animals; Swine; Equipment Design; Laparoscopy; Abdomen; Intestine, Small; Microsurgery
PubMed: 37995091
DOI: 10.1097/JS9.0000000000000911 -
Military Medical Research Oct 2023As the body's integumentary system, the skin is vulnerable to injuries. The subsequent wound healing processes aim to restore dermal and epidermal integrity and... (Review)
Review
As the body's integumentary system, the skin is vulnerable to injuries. The subsequent wound healing processes aim to restore dermal and epidermal integrity and functionality. To this end, multiple tissue-resident cells and recruited immune cells cooperate to efficiently repair the injured tissue. Such temporally- and spatially-coordinated interplay necessitates tight regulation to prevent collateral damage such as overshooting immune responses and excessive inflammation. In this context, regulatory T cells (Tregs) hold a key role in balancing immune homeostasis and mediating cutaneous wound healing. A comprehensive understanding of Tregs' multifaceted field of activity may help decipher wound pathologies and, ultimately, establish new treatment modalities. Herein, we review the role of Tregs in orchestrating the regeneration of skin adnexa and catalyzing healthy wound repair. Further, we discuss how Tregs operate during fibrosis, keloidosis, and scarring.
Topics: Humans; T-Lymphocytes, Regulatory; Wound Healing; Skin
PubMed: 37867188
DOI: 10.1186/s40779-023-00484-6