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Annals of Medicine and Surgery (2012) Jun 2024Although conversion arthroplasty of fused hips can relieve pain and provide patient satisfaction, long-term outcomes of total hip arthroplasty (THA) after hip fusion...
BACKGROUND
Although conversion arthroplasty of fused hips can relieve pain and provide patient satisfaction, long-term outcomes of total hip arthroplasty (THA) after hip fusion remain a subject of debate. This meta-analysis aimed to assess the effectiveness of THA for fused hips over a long period with concerns over potential complications.
METHODS
A systematic search of five databases from 2000 until 2023 identified English studies evaluating THA for fused hips with at least 100 months of follow-up. Meta-analyses were conducted using random-effect models via the comprehensive meta-analysis software. Sensitivity analysis, in-depth meta-regression, Egger's test, and the trim-and-fill method were performed appropriately.
RESULTS
The meta-analysis assessed 790 patients and 889 hips with a mean follow-up of 11 years. At the final follow-up, the mean Harris Hip Score (HHS) and leg length discrepancy (LLD) improved by 34.755 and 2.3 cm from the baseline, respectively. Regarding survival of hip fusion conversion to THA, most studies (88.8%) reported a 5-year implant survival rate of at least 90%, and the 15-year and 20-year implant survival rates, ranged between 80-90% and 70-90%, respectively. Subjective dissatisfaction with the conversion of hip fusion to THA was only 5.3%. Composite rates of revision, instability, and aseptic loosening were 13.6%, 3.8%, and 8.8%, respectively.
CONCLUSIONS
Conversion of fused hips to THA results in favourable long-term outcomes regarding HHS, LLD, survival rates, and subjective satisfaction, leading to improved quality of life in properly selected patients. However, the presence of complications should be considered when evaluating the overall success of the procedure.
PubMed: 38846831
DOI: 10.1097/MS9.0000000000002024 -
JTO Clinical and Research Reports Jun 2024The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials....
Efficacy and Safety of Anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Antibodies Plus Chemotherapy as First-Line Treatment for NSCLC in the People's Republic of China: a Systematic Review and Meta-Analysis.
INTRODUCTION
The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti-PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC.
METHODS
A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti-PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed.
RESULTS
There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival ( = 0.80), progression-free survival ( = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events ( = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo ( = 0.03).
CONCLUSIONS
Domestic anti-PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti-PD-1/PD-L1 antibodies based on current evidence.
PubMed: 38846810
DOI: 10.1016/j.jtocrr.2024.100678 -
Oncology Letters Jul 2024The present study compared the differences in effectiveness and safety between segmentectomy (ST) and wedge resection (WR) in patients with operable non-small cell lung...
Effectiveness and safety of segmentectomy vs. wedge resection for the treatment of patients with operable non‑small cell lung cancer: A meta‑analysis and systematic review.
The present study compared the differences in effectiveness and safety between segmentectomy (ST) and wedge resection (WR) in patients with operable non-small cell lung cancer (NSCLC). The PubMed, EMBASE, Cochrane Library and Web of Science databases were searched for papers published from inception until July 2023. The inclusion criteria were based on the population, intervention, comparator, outcomes and study designs. ROBINS-I was selected to assess the risk of bias and quality of evidence in the included non-randomised studies. Appropriate effect sizes were selected, and subgroup analyses, heterogeneity tests, sensitivity analyses and publication bias were applied. A total of 18 retrospective studies were included, involving 19,381 patients with operable NSCLC. The 5-year overall survival rate [hazard ratio (HR), 0.19; 95% confidence interval (CI), 0.04, 0.34; P=0.014; I=76.3%], lung cancer-specific survival rate (HR, 0.3; 95% CI, 0.21, 0.38; P<0.01; I=13.8%) and metastasis rate [odds ratio (OR), 1.56; 95% CI, 1.03, 2.38; P=0.037] in patients with operable NSCLC treated with WR were worse than those in patients treated with ST. The incidence of postoperative complications (OR, 0.44; 95% CI, 0.23, 0.82) in the WR group was lower than in the ST treatment group. There was no difference in postoperative recurrence (OR, 2.15; 95% CI, 0.97, 4.74; P=0.058) and mortality (risk difference, 0.04; 95% CI, -0.03, 0.11; P=0.287) between groups. Based on current evidence, patients with NSCLC treated with ST surgery have better postoperative survival but more complications than those patients treated with WT, while the effect of WR and ST on the recurrence rate and distant metastasis rate remains controversial.
PubMed: 38846430
DOI: 10.3892/ol.2024.14469 -
Endoscopy Jun 2024Several randomized controlled trials (RCTs) compared endoscopic ultrasound-guided biliary drainage (EUS-BD) to endoscopic retrograde cholangiopancreatography (ERCP) as...
BACKGROUND AND AIMS
Several randomized controlled trials (RCTs) compared endoscopic ultrasound-guided biliary drainage (EUS-BD) to endoscopic retrograde cholangiopancreatography (ERCP) as first-line interventions in distal malignant biliary obstruction (DMBO). We assessed the efficacy and safety of these two approaches.
METHODS
A PubMed/Medline, Embase and Cochrane databases bibliographic search until 01/12/2023 was performed to identify RCTs comparing EUS-BD to ERCP for primary biliary drainage in inoperable patients with DMBO. Primary outcome was technical success. Secondary outcomes were clinical success, adverse events (AEs), mean procedure time, 1-year stent patency, and overall survival. Relative risk (RR) with 95% confidence interval (CI) were calculated using random-effect model.
RESULTS
Five studies (519 patients) were included. The RR for pooled technical success in EUS-BD was 1.06 ([0.96-1.17]; P=0.27) and 1.02 [0.97-1.08]; P=0.45) for clinical success. 1-year stent patency was similar among the two groups (RR 1.15; [0.94-1.42], P=0.17), with lower reintervention in the EUS-BD group (RR 0.58; [0.37-0.9]; P=0.01). The RR of AEs rate was 0.85 [0.49-1.46]; P=0.55) and severe AEs of 0.97 [0.10-0.17]; P=0.98). On subgroup analysis, EUS-lumen apposing metal stents (LAMS) outperformed ERCP in term of technical success (RR 1.17; [1.01-1.35]; P=0.03). Procedure time was lower in EUS-BD (standardized mean difference -2.36 minutes; [-2.68 to -2.05]; P<0.001).
CONCLUSIONS
EUS-BD showed a statistically significant lower re-intervention rate compared to ERCP, but with similar technical success rate, stent patency, clinical success rate and safety profile, while in the subgroup of EUS-LAMS, the technical success was better than ERCP Keywords: distal; biliary obstruction; efficacy; safety.
PubMed: 38843824
DOI: 10.1055/a-2340-0697 -
European Journal of Physical and... Jun 2024Spinal cord injuries have a considerable impact on healthcare in terms of mortality and morbidity. To address the difficulties faced by people affected by this condition...
INTRODUCTION
Spinal cord injuries have a considerable impact on healthcare in terms of mortality and morbidity. To address the difficulties faced by people affected by this condition and to raise awareness among stakeholders and policymakers, it is crucial to understand factors impacting survival. The purpose of this study is to systematically review the literature on life expectancy in people with traumatic spinal cord injury (tSCI), identifying key factors influencing mortality and survival.
EVIDENCE ACQUISITION
We conducted a systematic review, searching the literature for articles published up to July 2023 in PubMed, Web of Science, Cochrane Library, Google Scholar, and PEDro. Study outcomes had to be one of survival rate, life expectancy, standardized mortality ratio, or mortality rate. Only original research articles published in English were included. The quality of evidence was evaluated with the MINORS scale. The level of evidence was categorized according to the OCEBM model.
EVIDENCE SYNTHESIS
A comprehensive literature search yielded 102 articles, after the selection process 20 studies were included in our review. The main factors negatively influencing survival and life expectancy included higher neurological level of injury (NLI), completeness of the lesion, need for mechanical ventilation, increasing age, and male gender. The development of SCI-related comorbidities also negatively impacted survival as well as the lack of specialized care, especially in low-income countries. Additionally, pre-injury health status and personal income may affect survival.
CONCLUSIONS
Current literature shows that people affected by tSCI have a shorter life expectancy compared to the general population, highlighting some factors as possible predictors. It is difficult to compare available evidence due to the methodological heterogeneity across studies, which makes it challenging to draw generalizable conclusions on life expectancy in people with tSCI. Further studies are required to address these issues and accurately estimate life expectancy accounting for gaps in the management of people affected by tSCI to improve their care.
PubMed: 38842067
DOI: 10.23736/S1973-9087.24.08462-4 -
Frontiers in Immunology 2024A single immune checkpoint inhibitor (ICI) regimen has limited value in treating advanced bile tract cancer (BTC); therefore, ICI combination therapy is often applied.... (Meta-Analysis)
Meta-Analysis
Clinical outcomes of immune checkpoint inhibitor combined with other targeted or immunological therapy regimens for the treatment of advanced bile tract cancer: a systematic review and meta-analysis.
BACKGROUND AND AIMS
A single immune checkpoint inhibitor (ICI) regimen has limited value in treating advanced bile tract cancer (BTC); therefore, ICI combination therapy is often applied. This meta-analysis aimed to evaluate the effectiveness and safety of ICI combination therapy for advanced BTC.
METHODS
The study protocol was registered on PROSPERO (CRD42023452422). Data on the median progression-free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR), and grade ≥3 adverse events (AEs) reported in relevant studies were pooled and analyzed to determine the efficacy and safety of ICI combination therapy.
RESULTS
In total, 15 studies with 665 patients were included in this meta-analysis. The overall ORR and DCR were 34.6% and 77.6%, respectively. The overall median PFS and OS were 6.06 months [95% confidence interval (CI): 4.91-7.21] and 12.11 months (95% CI: 10.66-13.55), respectively. Patients receiving ICI combination therapy in addition to other therapies had a considerably prolonged median PFS and OS (z=9.69, <0.001 and z=16.17, <0.001). Patients treated as first-line treatment had a substantially longer median PFS and OS compared to patients treated as non-first-line treatment (z=11.19, <0.001 and z=49.17, <0.001). The overall pooled grade ≥3 AEs rate was 38.2% (95% CI: 0.268-0.497) and was not influenced by whether ICI therapy was combined with other treatments or not or the treatment line.
CONCLUSION
Advanced BTC patients may benefit from ICI combination treatment without additional AEs. However, concurrent chemotherapy or radiotherapy is still needed to achieve better outcomes.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023452422.
Topics: Humans; Immune Checkpoint Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Biliary Tract Neoplasms; Immunotherapy
PubMed: 38840927
DOI: 10.3389/fimmu.2024.1378760 -
Heart, Lung & Circulation Jun 2024Aortic valve stenosis is a common cardiac condition that requires intervention for symptomatic and/or prognostic reasons. The two most common interventions are surgical...
The Clinical Impact of Paravalvular Leaks With Transcutaneous Aortic Valve Implantation (TAVI) Versus Surgical Aortic Valve Replacement (SAVR): A Systematic Review and Meta-Analysis.
BACKGROUND
Aortic valve stenosis is a common cardiac condition that requires intervention for symptomatic and/or prognostic reasons. The two most common interventions are surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). The ratio of TAVI:SAVR has increased twofold over the past few years and is now being considered in intermediate-risk patients as well. One of the significant benefits of TAVI is that it is less invasive; however, one of the drawbacks is a high paravalvular leaks (PVLs) rate compared to SAVR. To assess the impact of PVLs on survival, progression of heart failure, and the need for re-intervention.
METHOD
We conducted a comprehensive systematic literature search from the conception of TAVI 2002 until December 2022 through Embase (Ovid), MEDLINE (Ovid), Science Direct, and CENTRAL (Wiley). We followed PRISMA guidelines and checklists. Review protocol registration ID in PROSPERO: CRD42023393742.
RESULTS
We identified 28 studies that met our eligibility criteria, and only 24 studies were suitable for pooling in a meta-analysis (including their hazard ratio with a confidence interval of 95%) assessing our primary outcome (all-cause mortality). The remaining four studies were narratively synthesised. RevMan V5.4 (Version 5.4. Cochrane Collaboration, 2020) was utilised to pool meta-analysis data to assess effect estimates of PVLs in both intervention arms, using a random effect model for calculation (hazard ratio 1.14 confidence interval 95% 1.08-1.21 [p<0.0001]), with a follow-up duration between 30 days to 5 years.
CONCLUSION
Patients with mild or higher degrees of PVLs in both intervention arms incurred unfavourable outcomes. The incidence of PVLs was significantly higher with TAVI; even a mild degree led to poor quality of life and increased all-cause mortality on long-term follow-up.
PubMed: 38839468
DOI: 10.1016/j.hlc.2024.02.017 -
The Cochrane Database of Systematic... Jun 2024Hepatocellular carcinoma is the most common type of liver cancer, accounting for 70% to 85% of individuals with primary liver cancer. Gene therapy, which uses genes to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatocellular carcinoma is the most common type of liver cancer, accounting for 70% to 85% of individuals with primary liver cancer. Gene therapy, which uses genes to treat or prevent diseases, holds potential for treatment, especially for tumours. Trials on the effects of gene therapy in people with hepatocellular carcinoma have been published or are ongoing.
OBJECTIVES
To evaluate the benefits and harms of gene therapy in people with hepatocellular carcinoma, irrespective of sex, administered dose, and type of formulation.
SEARCH METHODS
We identified randomised clinical trials through electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We searched five online clinical trial registries to identify unpublished or ongoing trials. We checked reference lists of the retrieved studies for further trials. The date of last search was 20 January 2023.
SELECTION CRITERIA
We aimed to include randomised clinical trials assessing any type of gene therapy in people diagnosed with hepatocellular carcinoma, irrespective of year, language of publication, format, or outcomes reported.
DATA COLLECTION AND ANALYSIS
We followed Cochrane methodology and used Review Manager to prepare the review. The primary outcomes were all-cause mortality/overall survival (whatever data were provided), serious adverse events during treatment, and health-related quality of life. The secondary outcomes were proportion of people with disease progression, adverse events considered non-serious, and proportion of people without improvement in liver function tests. We assessed risk of bias of the included trials using RoB 2 and the certainty of evidence using GRADE. We presented the results of time-to-event outcomes as hazard ratios (HR), dichotomous outcomes as risk ratios (RR), and continuous outcomes as mean difference (MD) with their 95% confidence intervals (CI). Our primary analyses were based on intention-to-treat and outcome data at the longest follow-up.
MAIN RESULTS
We included six randomised clinical trials with 364 participants. The participants had unresectable (i.e. advanced inoperable) hepatocellular carcinoma. We found no trials assessing the effects of gene therapy in people with operable hepatocellular carcinoma. Four trials were conducted in China, one in several countries (from North America, Asia, and Europe), and one in Egypt. The number of participants in the six trials ranged from 10 to 129 (median 47), median age was 55.2 years, and the mean proportion of males was 72.7%. The follow-up duration ranged from six months to five years. As the trials compared different types of gene therapy and had different controls, we could not perform meta-analyses. Five of the six trials administered co-interventions equally to the experimental and control groups. All trials assessed one or more outcomes of interest in this review. The certainty of evidence was very low in five of the six comparisons and low in the double-dose gene therapy comparison. Below, we reported the results of the primary outcomes only. Pexastimogene devacirepvec (Pexa-Vec) plus best supportive care versus best supportive care alone There is uncertainty about whether there may be little to no difference between the effect of Pexa-Vec plus best supportive care compared with best supportive care alone on overall survival (HR 1.19, 95% CI 0.78 to 1.82; 1 trial (censored observation at 20-month follow-up), 129 participants; very low-certainty evidence) and on serious adverse events (RR 1.42, 95% CI 0.60 to 3.33; 1 trial at 20 months after treatment, 129 participants; very low-certainty evidence). The trial reported quality of life narratively as "assessment of quality of life and time to symptomatic progression was confounded by the high patient dropout rate." Adenovirus-thymidine kinase with ganciclovir (ADV-TK/GCV) plus liver transplantation versus liver transplantation alone There is uncertainty about whether ADV-TK/GCV plus liver transplantation may benefit all-cause mortality at the two-year follow-up (RR 0.39, 95% CI 0.20 to 0.76; 1 trial, 45 participants; very low-certainty evidence). The trial did not report serious adverse events other than mortality or quality of life. Double-dose ADV-TK/GCV plus liver transplantation versus liver transplantation alone There is uncertainty about whether double-dose ADV-TK/GCV plus liver transplantation versus liver transplantation may benefit all-cause mortality at five-year follow-up (RR 0.40, 95% CI 0.22 to 0.73; 1 trial, 86 participants; low-certainty evidence). The trial did not report serious adverse events other than mortality or quality of life. Recombinant human adenovirus-p53 with hydroxycamptothecin (rAd-p53/HCT) versus hydroxycamptothecin alone There is uncertainty about whether there may be little to no difference between the effect of rAd-p53/HCT versus hydroxycamptothecin alone on the overall survival at 12-month follow-up (RR 3.06, 95% CI 0.16 to 60.47; 1 trial, 48 participants; very low-certainty evidence). The trial did not report serious adverse events or quality of life. rAd-p53/5-Fu (5-fluorouracil) plus transarterial chemoembolisation versus transarterial chemoembolisation alone The trial included 46 participants. We had insufficient data to assess overall survival. The trial did not report serious adverse events or quality of life. E1B-deleted (dl1520) adenovirus versus percutaneous ethanol injection The trial included 10 participants. It did not report data on overall survival, serious adverse events, or health-related quality of life. One trial did not provide any information on sponsorship; one trial received a national research grant, one trial by the Pedersen foundation, and three were industry-funded trials. We found five ongoing randomised clinical trials.
AUTHORS' CONCLUSIONS
The evidence is very uncertain about the effects of gene therapy on the studied outcomes because of high risk of bias and imprecision of outcome results. The trials were underpowered and lacked trial data on clinically important outcomes. There was only one trial per comparison, and we could not perform meta-analyses. Therefore, we do not know if gene therapy may reduce, increase, or have little to no effect on all-cause mortality or overall survival, or serious adverse events in adults with unresectable hepatocellular carcinoma. The impact of gene therapy on adverse events needs to be investigated further. Evidence on the effect of gene therapy on health-related quality of life is lacking.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Randomized Controlled Trials as Topic; Genetic Therapy; Quality of Life; Bias; Male; Cause of Death; Female; Middle Aged
PubMed: 38837373
DOI: 10.1002/14651858.CD013731.pub2 -
Cancer Immunology, Immunotherapy : CII Jun 2024Numerous randomized controlled trials (RCTs) have investigated PD-1/PD-L1 inhibitor-based combination therapies. The debate surrounding the potential additive clinical... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of anti-PD-1/PD-L1-based dual immunotherapies versus PD-1/PD-L1 inhibitor alone in patients with advanced solid tumor: a systematic review and meta-analysis.
INTRODUCTION
Numerous randomized controlled trials (RCTs) have investigated PD-1/PD-L1 inhibitor-based combination therapies. The debate surrounding the potential additive clinical benefits of combination of two immune-oncology (IO) therapies for cancer patients persists.
METHODS
Both published and grey sources of randomized clinical trials that compared anti-PD-1/PD-L1-based immunotherapy combinations with monotherapy in patients with advanced or metastatic solid tumors were encompassed. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs).
RESULTS
Our analysis encompassed 31 studies comprising 10,341 patients, which covered 12 distinct immune-oncology combination regimens. Across all patients, the immunotherapy combinations exhibited the capability to enhance the ORR (OR = 1.23 [95% CI 1.13-1.34]) and extend PFS (HR = 0.91 [95% CI 0.87-0.95]). However, the observed enhancement in OS (HR = 0.96 [95% CI 0.91-1.01]) was of no significance. Greater benefits in terms of PFS (HR = 0.82 [95% CI 0.72 to 0.93]) and OS (HR = 0.85 [95% CI 0.73 to 0.99]) may be particularly pronounced in cases where PD-L1 expression is negative. Notably, despite a heightened risk of any-grade TRAEs (OR = 1.72 [95% CI 1.40-2.11]) and grade greater than or equal to 3 TRAEs (OR = 2.01 [95% CI 1.67-2.43]), toxicity was generally manageable.
CONCLUSIONS
This study suggests that incorporating an additional immunotherapy agent with PD-1/PD-L1 inhibitors can elevate the response rate and reduce the risk of disease progression, all while maintaining manageable toxicity. However, there remains a challenge in translating these primary clinical benefits into extended overall survival.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic
PubMed: 38834888
DOI: 10.1007/s00262-024-03734-1 -
Melanoma Research Jun 2024Eyelid melanoma (EM) is a malignant neoplasm accounting for around 1% of eyelid malignancies. Because of its rarity, most of our knowledge of EM is currently based on...
Eyelid melanoma (EM) is a malignant neoplasm accounting for around 1% of eyelid malignancies. Because of its rarity, most of our knowledge of EM is currently based on studies of cutaneous melanomas located elsewhere. Accordingly, this study aimed to specifically evaluate EM characteristics, management strategies, and prognosis. A retrospective study was carried out on patients diagnosed with EM at Careggi University Hospital, Florence between May 2012 and May 2022. In addition, a systematic review of relevant literature was conducted, encompassing studies published from 2013 to 2023. Clinical, histopathological, therapeutical, and prognostic data were analyzed to assess the metastasis rate and the 5-year survival rate of patients with EM. Separate data were extracted for in situ and invasive disease. Our original study included 19 patients diagnosed with EM with a 5-year survival rate of 100% for in situ and 83.3% for invasive EM. The literature review identified five poorly detailed large database reviews and 14 original studies on EM with an overall 5-year survival rate of 79.7%. The present research indicates that EM is a challenging malignancy, but has a relatively better prognosis and easier management than other melanomas of the head and neck region. These are probably related to the anatomical location which leads to early diagnosis. Therefore, EM should be considered as a specific disease requiring dedicated treatment. Based on the personal authors' experience and comprehensive overview of the current knowledge, a dedicated protocol is proposed.
PubMed: 38833343
DOI: 10.1097/CMR.0000000000000984