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AIMS: To evaluate patterns of recurrence and explore the prognostic differences between the 2018 FIGO staging system and the 2020 ESGO-ESTRO-ESP risk stratification system of endometrial cancer with an emphasis on early-stage disease. BACKGROUND: The incidence of endometrial cancer has risen by around 60% since the 90's. It is projected that by 2035 endometrial cancer will be the sixth most common cause of cancer-related death amongst females. METHODS: This was a retrospective cohort study which included patients treated between 2010 and 2017. Primary endpoints were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meyer survival analysis was used to assess OS and RFS across different risk groups. Cox proportional hazards regression was used to evaluate prognostic risk factors implicated in recurrence. Different recurrence patterns across the subgroups were analysed with Pearson's chi-square test. RESULTS: The study included 692 patients with a recurrence rate of 14.9%. The median time to recurrence was 17.1 months (IQR:8.8-28.4). The mean OS varied between 97.2 months in the low-risk group to 63.1 months in the high-risk group (p < 0.001). Mean RFS was 96.1 in the low-risk group and 58.9 in the high-risk group (p < 0.001). RFS was predicted by the following factors; high risk group (OR=3.87; p = 0.041), LVSI (OR=2.54, p = 0.005), carcinosarcoma (OR=2.20, p = 0.021) and serous subtype (OR=1.91, p = 0.01). Logistic regression was used to evaluate risk factors for loco-regional and distant recurrence. Patients in the low-risk group were less likely to have distant recurrence (OR=0.08, p = 0.004). Similarly, negative LVSI and Grade 1 cancers were associated with decreased risk of distant recurrence (OR=0.34, p = 0.006 and OR=0.33, p = 0.007, respectively). There were no significant risk factors for loco-regional recurrence. CONCLUSIONS: The 2020 ESGO-ESTRO-ESP risk stratification provides accurate estimates of recurrence risk and survival. Those treated in line with current guidance have significantly better outcomes.
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Ultrasonic waves can be used to transfer power and data efficiently through metallic enclosures when feedthroughs are not practical due to structural or electromagnetic shielding considerations. Previous implementations of ultrasonic power transfer (UPT) used a piezoelectric transducer permanently bonded to the metal for efficient ultrasonic coupling. For portable operation, it is essential to have a detachable transmitter (charger) that is only attached to the enclosure while transferring power. This requirement presents several design challenges; notably, detachable ultrasonic coupling typically relies on liquid or gel couplant, which may become inconvenient or less robust during repeated attachment and detachment. Thus, this work develops a dry-coupled detachable UPT system to transfer power efficiently through a metallic enclosure without the need for a liquid couplant. Low attenuation soft elastomers are experimentally tested with a magnetic setup to evaluate their dry-coupled efficiency. Samples with different materials and thicknesses are experimentally tested to select the best configuration for dry ultrasonic coupling. The softest elastomer tested yielded the best ultrasonic efficiency (AC-to-AC) of 68% at 1 MHz. A full DC-to-DC portable (battery-operated) UPT system was then developed and experimentally characterized. The system was capable of delivering up to 3 W of DC power to a resistive load with a total efficiency of 50%.
ABSTRACT
BACKGROUND: Optimizing immune checkpoint inhibitor (ICI) therapy may require identification of co-targetable checkpoint pathways via immune profiling. Herein, we analyzed the transcriptomic expression and clinical correlates of V-domain immunoglobulin suppressor of T-cell activation (VISTA), a promising targetable checkpoint. PATIENTS AND METHODS: RNA sequencing was carried out on 514 tissues reflecting diverse advanced/metastatic cancers. Expression of eight immune checkpoint markers [lymphocyte-activation gene 3 (LAG-3), tumor necrosis factor receptor superfamily 14 (TNFRSF14), programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), B- and T-lymphocyte attenuator (BTLA), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), cytotoxic T-lymphocyte antigen 4 (CTLA-4)], in addition to VISTA, was analyzed, along with clinical outcomes. RESULTS: High VISTA RNA expression was observed in 32% of tumors (66/514) and was the most common highly expressed checkpoint among the nine assessed. High VISTA expression was independently correlated with high BTLA, TIM-3, and TNFRSF14, and with a diagnosis of pancreatic, small intestine, and stomach cancer. VISTA transcript levels did not correlate with overall survival (OS) from metastatic/advanced disease in the pan-cancer cohort or with immunotherapy outcome (progression-free survival and OS from the start of ICI) in 217 ICI-treated patients. However, in ICI-treated pancreatic cancer patients (n = 16), median OS was significantly shorter (from immunotherapy initiation) for the high- versus not-high-VISTA groups (0.28 versus 1.21 years) (P = 0.047); in contrast, VISTA levels were not correlated with OS in 36 pancreatic cancer patients who did not receive ICI. CONCLUSION: High VISTA expression correlates with high BTLA, TIM-3, and TNFRSF14 checkpoint-related molecules and with poorer post-immunotherapy survival in pancreatic cancer, consistent with prior literature indicating that VISTA is prominently expressed on CD68+ macrophages in pancreatic cancers and requiring validation in larger prospective studies. Immunomic analysis may be important for individualized precision immunotherapy.
Subject(s)
B7 Antigens , Neoplasms , Humans , Neoplasms/immunology , B7 Antigens/metabolism , Male , Female , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Middle Aged , Biomarkers, Tumor/metabolism , Immune Checkpoint Proteins/metabolism , AgedABSTRACT
AIMS: The aim of this study was to establish a baseline of national practice for follow-up after treatment for endometrial cancer in the UK. MATERIALS AND METHODS: An online cross-sectional survey was developed and distributed through the Royal College of Radiologists via an email link to the audit leads of radiotherapy centres in the UK. The survey was conducted from November 2021 to 5 January 2022. The main themes assessed in the survey were the form, frequency and duration of follow-up practices. RESULTS: There were a total of 43/61 (70%) complete responses. 93% of centres had a standard follow-up protocol and 7% who did not have a follow-up protocol discharged patients after the post-operative review. Five centres (13%) used molecular profiling to inform follow-up practices. Patient-initiated follow-up was mainly used in the cohort of patients who had surgery alone with no adjuvant treatment (68%, (19/28)). In the cohort who had face-to-face follow-up, the majority had pelvic examinations as part of their review and total follow-up for five years. 93% of respondents are interested in a national follow-up protocol. CONCLUSION: Our data shows that there is national variation in practise with regard to follow-up of women treated for endometrial cancer. Many of the follow-up practises are based on conventional follow-up regimens and these may fail to address the more holistic needs of cancer survivors. Recent publication of updated guidance from the British Gynaecological Cancer Society may help standardise practise and provide a more relevant approach to follow-up for women treated for endometrial cancer.
Subject(s)
Endometrial Neoplasms , Humans , Female , Endometrial Neoplasms/therapy , Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , United Kingdom , Cross-Sectional Studies , Surveys and Questionnaires , Follow-Up Studies , Practice Patterns, Physicians'/statistics & numerical data , Aftercare/standardsABSTRACT
AIM: The aim of this work was to evaluate colorectal cancer (CRC) outcomes after 'low' (sub-threshold) faecal immunochemical test (FIT) results in symptomatic patients tested in primary care. METHOD: This work comprised a retrospective audit of 35 289 patients with FIT results who had consulted their general practitioner with lower gastrointestinal symptoms and had subsequent CRC diagnoses. The Rapid Colorectal Cancer Diagnosis pathway was introduced in November 2017 to allow incorporation of FIT into clinical practice. The local '4F' protocol combined FIT results with blood tests and digital rectal examination (DRE): FIT, full blood count, ferritin and finger [DRE]. The outcome used was detection rates of CRC, missed CRC and time to diagnosis in local 4F protocols for patients with a subthreshold faecal haemoglobin (fHb) result compared with thresholds of 10 and 20 µg Hb/g faeces. RESULTS: A single threshold of 10 µg Hb/g faeces identifies a population in whom the risk of CRC is 0.2%, but this would have missed 63 (10.5%) of 599 CRCs in this population. The Nottingham 4F protocol would have missed fewer CRCs [42 of 599 (7%)] despite using a threshold of 20 µg Hb/g faeces for patients with normal blood tests. Subthreshold FIT results in patients subsequently diagnosed with a palpable rectal tumour yielded the longest delays in diagnosis. CONCLUSION: A combination of FIT with blood results and DRE (the 4F protocol) reduced the risk of missed or delayed diagnosis. Further studies on the impact of such protocols on the diagnostic accuracy of FIT are expected. The value of adding blood tests to FIT may be restricted to specific parts of the fHb results spectrum.
Subject(s)
Colorectal Neoplasms , Rectal Neoplasms , Humans , Colorectal Neoplasms/pathology , Sensitivity and Specificity , Retrospective Studies , Hemoglobins/analysis , Colonoscopy , Feces/chemistry , Occult Blood , Early Detection of Cancer/methodsSubject(s)
Analgesia, Epidural , Analgesia, Obstetrical , Anesthesia, Epidural , Anesthesia, Obstetrical , Anesthesia, Spinal , Labor, Obstetric , Pregnancy , Female , Humans , Anesthesia, Spinal/adverse effects , Patient Transfer , Catheters/adverse effects , Anesthesia, Obstetrical/adverse effectsABSTRACT
A serious complication in aortic dissection is dynamic obstruction of the true lumen (TL). Dynamic obstruction results in malperfusion, a blockage of blood flow to a vital organ. Clinical data reveal that increases in central blood pressure promote dynamic obstruction. However, the mechanisms by which high pressures result in TL collapse are underexplored and poorly understood. Here, we developed a computational model to investigate biomechanical and hemodynamical factors involved in Dynamic obstruction. We hypothesize that relatively small pressure gradient between TL and false lumen (FL) are sufficient to displace the flap and induce obstruction. An idealized fluid-structure interaction model of type B aortic dissection was created. Simulations were performed under mean cardiac output while inducing dynamic changes in blood pressure by altering FL outflow resistance. As FL resistance increased, central aortic pressure increased from 95.7 to 115.3 mmHg. Concurrent with blood pressure increase, flap motion was observed, resulting in TL collapse, consistent with clinical findings. The maximum pressure gradient between TL and FL over the course of the dynamic obstruction was 4.5 mmHg, consistent with our hypothesis. Furthermore, the final stage of dynamic obstruction was very sudden in nature, occurring over a short time (<1 s) in our simulation, consistent with the clinical understanding of this dramatic event. Simulations also revealed sudden drops in flow and pressure in the TL in response to the flap motion, consistent with first stages of malperfusion. To our knowledge, this study represents the first computational analysis of potential mechanisms driving dynamic obstruction in aortic dissection.
Subject(s)
Aortic Dissection , Humans , Blood Pressure , Hemodynamics , Computer SimulationABSTRACT
INTRODUCTION: Recent evidence suggests that acute emergency management of mandible fractures does not improve surgical outcomes yet is associated with increased financial burden. Current NHS policy advocating for increased adoption of day-case and semi-elective surgical procedures to reduce bed strain must be balanced with providing timely, effective treatment. Our research aims to determine patient groups currently managed via semi-elective admission and whether this can be extended to other groups to provide safe and effective management of mandible fractures. METHODS: A multi-national trainee-led audit of mandibular fractures across 49 units was completed by the Maxillofacial Trainee Research Collaborative (MTReC). Each unit prospectively collected data on fractures on admission and at follow-up. Data collected included patient demographics, behaviour, health, injury, timing to intervention and surgical complications. RESULTS: Data were collected on 947 mandibular fractures. Of the surgically managed patients, 649 (90%) were managed via acute emergency admission at the time of presentation, while 68 (10%) were managed semi-electively. Patient demographics, injury pattern and mechanism appeared to significantly affect timing of management, whereas patient behaviour, health status, timing of injury and presentation did not. Semi-elective management was associated with a significantly shorter inpatient duration (0.9 versus 1.9 days, p=0.000) with no differences in readmission, antibiotic usage or surgical complications (p=1.000, RR 1.030). CONCLUSION: Our study demonstrates the efficacy of planned admissions and semi-elective management of mandibular fractures. Simple mandibular fractures in compliant patients are suitable for semi-elective treatment. Holistic patient assessment and tailored surgical planning is crucial in determining admission modality to effectively manage mandibular trauma.
Subject(s)
Mandibular Fractures , Humans , Mandibular Fractures/surgery , Fracture Fixation, Internal/methods , Anti-Bacterial Agents , Treatment Outcome , Mandible , Retrospective StudiesABSTRACT
Additive manufacturing of alloys enables low-volume production of functional metallic components with complex geometries. Ultrasonic testing can ensure the quality of these components and detect typical defects generated during laser powder bed fusion (LPBF). However, it is difficult to find a single ultrasonic inspection technique that can detect defects in the large variety of geometries generated using LPBF. In this work, phased array ultrasonic testing (PAUT) is suggested to inspect thick LPBF components, while guided waves are explored for thin curved ones. PAUT is used to detect cylindrical lack of fusion defects in thick LPBF rectangular parts. Practical defects are generated by reducing the laser power at prespecified locations in the samples. The defects' shape and density are verified using optical microscopy and X-ray computed tomography. Partially fused defects down to 0.25 mm in diameter are experimentally detected using a 10 MHz PAUT probe with the total focusing method post-processing. The experimental results are compared to defect images predicted by finite element simulations. For thin components with curved geometry, guided waves are used to detect powder-filled cylindrical defects. The waves are generated using piezoelectric transducers, and the spatiotemporal wavefield is measured using a scanning laser Doppler vibrometer. Using root-mean-square imaging of the wavefield, defects down to 1 mm are clearly detected despite the complex internal features in the samples.
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PURPOSE: To investigate whether use of an enema prep reduces the false-negative (FN) rate of PI-RADS 1 MRI of the prostate for clinically significant prostate cancer (csPCa). MATERIALS AND METHODS: 1108 consecutive patients with a PI-RADS 1 MRI performed 01/2016-09/2021 were retrospectively collected. Patient charts were examined for subsequent systematic prostate biopsy performed within 1 year if positive or anytime thereafter if negative. Patients without biopsy were excluded. Use of an enema prep 1-2 h before MRI, which was implemented in 03/2019, was recorded. FN rate of MRI for detection of csPCa, defined as Gleason score ≥ 7, using systematic biopsy was assessed per patient and compared between those with and without an enema prep. Χ2 test and logistic regression were performed. RESULTS: 255 patients (median age 64, IQR 58-69) with median PSA 5.6 (IQR 4.2-8.1), PI-RADS 1 MRI, and subsequent biopsy were included in the analysis. 66 patients (26%) had an enema prep and 189 patients (74%) did not. 7 (11%) patients with and 21 (11%) patients without enema prep had a FN biopsy. There was no significant association between enema prep and FN biopsy (OR 0.95, 95% CI 0.38-2.35, p = 0.91). CONCLUSIONS: Use of an enema prep prior to prostate MRI did not decrease the FN rate of PI-RADS 1 MRI of the prostate for clinically significant prostate cancer.
Subject(s)
Prostate , Prostatic Neoplasms , Enema , Humans , Image-Guided Biopsy , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Grading , Prostate/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Retrospective StudiesABSTRACT
Several disorders associated with the total or partial absence of components of the human complement system are known. Deficiencies of classical pathway (CP) components are generally linked to systemic lupus erythematosus (SLE) or SLE-like syndromes. However, only approximately one-third of patients who lack C2 show mild symptoms of SLE. The relatively high frequency of homozygous C2 deficiency without or with minor disease manifestation suggests that there might be a compensatory mechanism which allows the activation of the CP of complement without the absolute requirement of C2. In this study we show that factor B (FB), the C2 homologue of the alternative pathway (AP) of complement, can substitute for C2. This was confirmed by using C4b as immobilised ligand and FB as analyte in Surface Plasmon Resonance (BIACORE). C2 binding to the immobilised C3b-like molecule C3(CH3NH2) was not seen. The estimated binding constant for C4bB complex formation was 2.00 * 10-5 [M]. We were further able to demonstrate that C4b supports the cleavage of Factor B by Factor D. Finally, cleavage of 125I-C3 by C4bBb was evaluated and gave strong evidence that the "hybrid" convertase C4bBb can cleave and activate C3 in vitro. Cleavage activity is very low, but consistent with some of the "C2-bypass" observations of others.
Subject(s)
Complement C4 , Lupus Erythematosus, Systemic , Complement Activation , Complement C2/metabolism , Complement C3/metabolism , Complement C3-C5 Convertases/metabolism , Complement C3b , Complement Factor B , Complement Pathway, Classical , HumansABSTRACT
AIM: To review the experience of penetrating injury and its subsequent imaging and to discuss imaging strategies in overall trauma management in a paediatric major trauma centre. MATERIALS AND METHODS: A retrospective, single-centre study was conducted over a 4-year period (1/1/16-31/12/19) of children (<16 years old) presenting to the Emergency Department with penetrating trauma. Clinical, radiographic, and demographic data were analysed using descriptive statistics. RESULTS: Fifty-eight patients in >60 attendances were reviewed. Most (44/60, 73%) underwent some imaging, with almost half (28/60, 47%) having both computed tomography (CT) and radiography. Of cases with only a single injury site (35/60, 58%), CT was performed in 19/35 (54%) with 13/19 (68%) covering more than one body area. Of the multi-injury site cases (26/60, 42%), CT was performed in 16/25 (64%) with 14/16 (88%) involving multiple body areas. The most common injuries were solid-organ lacerations and soft-tissue and vascular injuries according to body site involved. CONCLUSION: Contrast-enhanced CT across multiple body parts should be performed for multiple stab wounds or visible injuries involving the torso. Isolated penetrating injuries may only require CT of a single body part unless the entry wound crosses body parts. An imaging algorithm is suggested, which may be applicable to other paediatric trauma units.
Subject(s)
Multiple Trauma , Wounds, Penetrating , Wounds, Stab , Adolescent , Child , Humans , Retrospective Studies , Trauma Centers , United Kingdom/epidemiology , Wounds, Penetrating/diagnostic imaging , Wounds, Penetrating/epidemiologyABSTRACT
The FDA granted expedited approval for Johnson and Johnson's Bedaquiline to treat pulmonary multidrug resistant tuberculosis on 28 December 2012 which is more common in China, Russian Federation and India. Bedaquiline is the first anti-tubercular drug approved by the FDA in the last 40 years, and it has become a cynosure in the circles of synthetic chemists researching new anti-tubercular drugs. Bedaquiline's highly lipophilic nature raises major concerns like suppression of the hERG gene, hepatotoxicity, and phospholipidosis despite its potential antitubercular profile. To address these toxicity concerns, in the present work, we have employed the structural optimization of Bedaquiline using the ADMETopt web server, which optimizes lead with scaffold hopping and ADMET screening. The ADMETopt web server yielded the 476 structures through optimization of three sites in Bedaquiline. Further, we have validated the optimized structures for their activity by performing molecular docking and molecular dynamics (MD) simulations against the mycobacterial ATP synthase enzyme and density functional theory (DFT) study further provides insight into the reactivity of the compounds. After screening and analysis, compound #449 was observed to be the most promising mycobacterial ATP synthase inhibitor with minimal cardiotoxicity, hepatotoxicity and phospholipidosis.
Subject(s)
Cheminformatics , Quantitative Structure-Activity Relationship , Antitubercular Agents/chemistry , Diarylquinolines/chemistry , Diarylquinolines/toxicity , Molecular Docking SimulationABSTRACT
During the COVID-19 pandemic, people may use substances like cannabis for enhancement or coping purposes. Behavioral economic demand for a substance is a key determinant of its use and misuse and can be measured via hypothetical purchase tasks. Previous research suggests that motivations to use a substance play a mediational role between elevated substance demand and problems, but comparable mechanistic research has yet to be done in the COVID-19 context and on the effects of cannabis demand on cannabis use patterns. Participants (n = 137) were recruited via the online crowdsourcing platform Prolific. Participants completed measures of cannabis use and problems, motivations for cannabis use, and the Marijuana Purchase Task. Two indices of demand, Persistence (i.e., sensitivity to increasing cost of cannabis) and Amplitude (i.e., consumption of cannabis at unrestricted cost), were related to increased cannabis problems via the use motive of coping during the COVID-19 pandemic. This model did not support the mediational role of enhancement motives. Those with increased cannabis demand who tend to use cannabis to cope are at increased risk of experiencing negative cannabis-related consequences during the COVID-19 pandemic.
Subject(s)
COVID-19 , Cannabis , Adaptation, Psychological , Humans , Motivation , Pandemics , SARS-CoV-2ABSTRACT
BACKGROUND: Psoriasis, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are chronic inflammatory diseases that often affect women of childbearing age. Detailed information about pregnancy and related outcomes across these indications in patients exposed to ixekizumab is lacking. OBJECTIVES: To evaluate pregnancy outcomes after maternal or paternal exposure to ixekizumab in patients with psoriasis, PsA, or axSpA. METHODS: Pregnancy cases from clinical trials and post-marketing reports, associated with either maternal or paternal exposure to ixekizumab cumulatively through 22 March 2019, were identified in the Eli Lilly Global Safety Database and described separately. RESULTS: One hundred and ninety-three ixekizumab-exposed pregnancies were identified. Maternal exposure occurred in 51.3% of pregnancies (clinical trials: n = 58; post-marketing: n = 41). The majority of paternal exposure pregnancies occurred in clinical trials (91 of 94). Live births were reported for 53.8 and 61.1% of known outcomes in maternal exposure pregnancies during clinical trials and post-marketing surveillance, respectively. No congenital malformations resulting from maternal exposure were reported in clinical trials: one case, not causally related to ixekizumab therapy, was recorded in the post-marketing setting. CONCLUSIONS: This integrated safety analysis provides relevant information for clinicians treating patients with psoriasis, PsA, or axSpA with ixekizumab. No new safety signals were identified in patients receiving ixekizumab.
Subject(s)
Arthritis, Psoriatic , Axial Spondyloarthritis , Psoriasis , Antibodies, Monoclonal, Humanized , Arthritis, Psoriatic/drug therapy , Female , Humans , Male , Pregnancy , Pregnancy Outcome , Psoriasis/drug therapy , Treatment OutcomeABSTRACT
The musculoskeletal conditions osteoporosis and sarcopenia are highly prevalent in older adults. Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone, whereas sarcopenia is identified by the loss of muscle strength, function and mass. Osteoporosis represents a major health problem contributing to millions of fractures worldwide on an annual basis, whereas sarcopenia is associated with a range of adverse physical and metabolic outcomes. They both affect physical and social function, confidence and quality of life as well as contributing to high health-care costs worldwide. Osteosarcopenia is the term given when both conditions occur concomitantly and it has been suggested that interactions between these two conditions may accelerate individual disease progression as co-existence of osteoporosis and sarcopenia is associated with higher morbidity from falls, fracture, disability as well as mortality. In this review, we will outline the epidemiology, pathogenesis and clinical consequences of osteosarcopenia and discuss available management strategies.
Subject(s)
Fractures, Bone , Osteoporosis , Sarcopenia , Aged , Humans , Muscle Strength , Osteoporosis/complications , Osteoporosis/epidemiology , Quality of Life , Sarcopenia/epidemiologyABSTRACT
The incidence of external ventricular drain (EVD) infections remains high. Chlorhexidine dressings have demonstrated efficacy in reducing infections associated with indwelling catheters at other body sites, although evidence for their use with EVDs is limited. The aim of this systematic review and meta-analysis was to evaluate the efficacy of chlorhexidine dressings in reducing EVD-associated cerebrospinal fluid infection (EVDAI). MEDLINE, EMBASE and the Cochrane library were queried for articles from inception. The primary outcome was the incidence of EVDAI. Secondary outcomes included device safety, microbiological outcomes and shunt-dependency. From 896 unique records, five studies were included of which four presented suitable data for quantitative analysis including three case series and one underpowered randomized controlled trial. There was a high risk of bias in all studies. A total of 880 patients were included with a mean age of 57.7 years (95% confidence interval (CI) 57.4-58.0 years). In primary outcome analysis, the chlorhexidine dressing group had a significantly lower incidence of EVDAI (1.7% vs 7.9%, risk difference (RD) = 0.07, 95% CI 0.00-0.13, P=0.04). In conclusion, chlorhexidine dressings may reduce the incidence of EVDAI but require future study in randomized trials to definitively determine efficacy.