Revisiting Level of Evidence Ratings in Plastic Surgery: A Call to Action.

BACKGROUND: Evidence-based medicine underpins medical and surgical practice, with level of evidence (LOE) being a key aspect that allows clinicians and researchers to better discriminate the methodological context by which studies are conducted and appropriately interpret their conclusions, and more specifically the strength of their recommendations. OBJECTIVES: The aim of this study was to reassess the LOE of articles published in plastic surgery journals. METHODS: To assess the overall LOE of publications from January 1 to December 31, 2021, a review of the following plastic surgery journals was performed: Aesthetic Surgery Journal (ASJ), Annals of Plastic Surgery (Annals), Journal of Plastic Reconstructive and Aesthetic Surgery (JRPAS), Plastic and Reconstructive Surgery (PRS), and Plastic and Reconstructive Surgery Global Open (PRS GO). RESULTS: Of 3698 PUBMED articles, 1649 original articles and systematic reviews were analyzed. The average LOE for each journal was: ASJ 3.02 ± 0.94, Annals 3.49 ± 0.62, JPRAS 3.33 ± 0.77, PRS 2.91 ± 0.77, and PRS GO 3.45 ± 0.70. The collective average LOE was 3.28 ± 0.78. Only 4.4% were LOE 1 and 7.3% were LOE 2. Compared to past studies, PRS showed a significant LOE improvement (P = .0254), while ASJ and JPRAS saw nonsignificant changes; Annals experienced a significant decrease (P = .0092). CONCLUSIONS: ASJ and PRS showed the highest LOE among the journals analyzed. Despite this, low LOE studies remain prevalent in plastic surgery. This paper serves as a call to action for both researchers and academic journals to elevate the standard, offering several strategies to help improve the LOE in plastic surgery.

The reproducibility of breathing maneuvers as a vasoactive stimulus in the heart: an oxygenation-sensitive resonance imaging study.

BACKGROUND: Endothelial dysfunction and impaired oxygenation of the heart is a hallmark of several diseases, including coronary artery disease, hypertension, diabetes, and sleep apnea. Recent studies indicate that oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) imaging combined with breathing maneuvers may allow for assessing coronary vascular responsiveness as a marker for coronary vascular function in various clinical settings. However, despite the use of OS-CMR in evaluating tissue oxygenation, the reproducibility of these standardized, combined breathing maneuvers as a vasoactive stimulus has yet to be systematically assessed or validated. In this study, we aimed to assess the reproducibility of vasoactive breathing maneuvers to assess vascular function in a population of healthy volunteers. METHODS: Eighteen healthy volunteers were recruited for the study. Inclusion criteria were an age over 18 years and absence of any evidence or knowledge of cardiovascular, neurological, or pulmonary disease. MRI was performed on a clinical 3 T MRI system (MAGNETOM Skyra, Siemens Healthineers, Erlangen, Germany). The OS-CMR acquisition was performed as previously described (1 min hyperventilation followed by a maximal, voluntary breath-hold). Standard statistical tests were performed as appropriate. RESULTS: Data from 18 healthy subjects was analyzed. The healthy volunteers had a mean age of 42 ± 15 years and a mean BMI of 25.4 ± 2.8 kg/m2, with an average heart rate of 72 ± 11 beats per minute, and ten of whom (56%) were female. There were no significant differences between global myocardial oxygenation (%[Formula: see text] SI) after hyperventilation (HV1: - 7.82 [Formula: see text] 5.2; HV2: - 7.89 [Formula: see text] 6.4, p = 0.9) or breath-hold (BH1: 5.34 [Formula: see text] 3.1; BH2: 6.0 [Formula: see text] 3.3, p = 0.5) between the repeated breathing maneuvers. The Bland-Altman analysis showed good agreement (bias: 0.074, SD of bias: 2.93). CONCLUSION: We conclude that in healthy individuals, the myocardial oxygenation response to a standardized breathing maneuver with hyperventilation and a voluntary breath-hold is consistent and highly reproducible. These results corroborate previous evidence for breathing-enhanced OS-CMR as a robust test for coronary vascular function.

Microvascular Dysfunction as a Possible Link Between Heart Failure and Cognitive Dysfunction.

BACKGROUND: Microvascular function in the brain and heart may play an important role in the course of patients with heart failure (HF), but its relationship with ventricular and cognitive function is not well understood. We hypothesized that microvascular function in HF is closely related to both, cardiac and cognitive function. METHODS: In healthy controls and symptomatic patients with HF (New York Heart Association functional class II or III), we used oxygenation-sensitive magnetic resonance imaging during a standardized breathing maneuver to determine the cerebral oxygenation reserve and the myocardial oxygenation reserve (MORE) as markers for microvascular function. A stepwise multivariable linear regression was performed to determine the variables that best predict changes in cerebral oxygenation reserve and MORE. We also measured cognitive function using the Montreal Cognitive Assessment test. RESULTS: Twenty patients with HF (age 64.4±8.3 years; 50% female sex), and 21 healthy controls (age 55.0±5.1 years; 62% female sex) were included in the analysis. In patients with HF, cerebral oxygenation reserve and MORE were lower than in healthy controls (MORE, -0.1±3.3 versus 5.0±4.2, cerebral oxygenation reserve: 0.43±0.47 versus 1.21±0.60, respectively) as were Montreal Cognitive Assessment score results (HF, 23.9±3.7; healthy, 27.8±1.5; P=0.002). The Montreal Cognitive Assessment score in patients was correlated with cardiac output (r=0.55, P=0.011) and MORE (r=0.46, P=0.040). In addition to the presence of HF, significant predictors of cerebral and myocardial oxygenation reserve were cardiac output and end-diastolic volume, respectively. CONCLUSIONS: Our results indicate that heart failure is an independent predictor of coronary and cerebral microvascular dysfunction as defined by a reduced response to a vasodilatory breathing maneuver. This impaired response was associated with reduced cognitive function.

Practical Review on Delayed Primary Closure: Basic Science and Clinical Applications.

Wound healing complications present a significant burden on both patients and health-care systems, and understanding wound healing principles is crucial across medical and surgical specialties to help mitigate such complications. One of these longstanding principles, specifically delayed primary closure (DPC), described as mechanically closing a wound after several days of secondary intention healing, lacks clear consensus on its definition, indications, and outcomes. This practical review examines wound healing fundamentals, focusing on DPC, its execution, indications, and comparative outcomes. A PubMed literature search was conducted to retrieve studies on DPC. Inclusion criteria included comparative studies assessing outcomes and complications between DPC and other closure techniques, as well as articles investigating DPC's underlying physiology. Twenty-three comparative studies met inclusion criteria. DPC wounds have significantly higher partial pressure of oxygen, higher blood flow, and higher rates of collagen synthesis and remodeling activity, all of which help explain DPC wounds' superior mechanical strength. DPC seems most beneficial in contaminated wounds, such as complicated appendectomies, postcardiac surgery wounds, and complicated abdominal wall reconstructions, where it has been associated with lower rates of surgical site infections. This practical review provides an evidence-based approach to DPC, its physiology, technique, and indications. Based on the existing literature, the authors recommend that DPC wounds should be dressed in saline/betadine soaks, changed and irrigated daily, with delayed closure lasting between 3 and 5 days or until the infection has resolved. The clearest indications for DPC are in the context of contaminated abdominal surgery and sternal wound dehiscence post cardiac surgery.

Oxygenation-sensitive Cardiac MRI with Vasoactive Breathing Maneuvers for the Non-invasive Assessment of Coronary Microvascular Dysfunction.

Oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) is a diagnostic technique that uses the inherent paramagnetic properties of deoxyhemoglobin as an endogenous source of tissue contrast. Used in combination with standardized vasoactive breathing maneuvers (hyperventilation and apnea) as a potent non-pharmacologic vasomotor stimulus, OS-CMR can monitor changes in myocardial oxygenation. Quantifying such changes during the cardiac cycle and throughout vasoactive maneuvers can provide markers for coronary macro- and microvascular function and thereby circumvent the need for any extrinsic, intravenous contrast or pharmacologic stress agents. OS-CMR uses the well-known sensitivity of T2*-weighted images to blood oxygenation. Oxygenation-sensitive images can be acquired on any cardiac MRI scanner using a modified standard clinical steady-state free precession (SSFP) cine sequence, making this technique vendor-agnostic and easily implemented. As a vasoactive breathing maneuver, we apply a 4 min breathing protocol of 120 s of free breathing, 60 s of paced hyperventilation, followed by an expiratory breath-hold of at least 30 s. The regional and global response of myocardial tissue oxygenation to this maneuver can be assessed by tracking the signal intensity change. The change over the initial 30 s of the post-hyperventilation breath-hold, referred to as the breathing-induced myocardial oxygenation reserve (B-MORE) has been studied in healthy people and various pathologies. A detailed protocol for performing oxygen-sensitive CMR scans with vasoactive maneuvers is provided. As demonstrated in patients with microvascular dysfunction in yet incompletely understood conditions, such as inducible ischemia with no obstructive coronary artery stenosis (INOCA), heart failure with preserved ejection fraction (HFpEF), or microvascular dysfunction after heart transplantation, this approach provides unique, clinically important, and complementary information on coronary vascular function.

Synthesis of 2,5-Diaryl Nonsymmetric Furans C6-Platform Chemicals via Catalytic Conversion of Biomass and the Formal Synthesis of Dantrolene.

Biomass-derived commodity chemical 5-hydroxymethyl furfural is an underutilized C6-platform chemical derived from cellulose that is ideal to prepare next-generation value-added products. We have developed an efficient synthetic strategy to access 2,5-diaryl nonsymmetric furans from 5-hydroxymethyl furfural utilizing decarboxylative cross-couplings. A key finding was that the presence of the hydroxymethyl handle enhances the yields of the palladium-catalyzed decarboxylative cross-coupling reaction. The method provides access to a broad-range nonsymmetric 2,5-diaryl furans where each arene can be systematically introduced as required. Additionally, this green synthetic strategy was employed for a formal synthesis of the muscle relaxant Dantrolene in excellent yields.

A High-Throughput Glycosyltransferase Inhibition Assay for Identifying Molecules Targeting Fucosylation in Cancer Cell-Surface Modification.

In cancers, increased fucosylation (attachment of fucose sugar residues) on cell-surface glycans, resulting from the abnormal upregulation of the expression of specific fucosyltransferase enzymes (FUTs), is one of the most important types of glycan modifications associated with malignancy. Fucosylated glycans on cell surfaces are involved in a multitude of cellular interactions and signal regulation in normal biological processes, as well as in disease. For example, sialyl LewisX is a fucosylated cell-surface glycan that is abnormally abundant in some cancers where it has been implicated in facilitating metastasis, allowing circulating tumor cells to bind to the epithelial tissue within blood vessels and invade into secondary sites by taking advantage of glycan-mediated interactions. To identify inhibitors of FUT enzymes as potential cancer therapeutics, we have developed a novel high-throughput assay that makes use of a fluorogenically labeled oligosaccharide as a probe of fucosylation. This probe, which consists of a 4-methylumbelliferyl glycoside, is recognized and hydrolyzed by specific glycoside hydrolase enzymes to release fluorescent 4-methylumbelliferone, yet when the probe is fucosylated prior to treatment with the glycoside hydrolases, hydrolysis does not occur and no fluorescent signal is produced. We have demonstrated that this assay can be used to measure the inhibition of FUT enzymes by small molecules, because blocking fucosylation will allow glycosidase-catalyzed hydrolysis of the labeled oligosaccharide to produce a fluorescent signal. Employing this assay, we have screened a focused library of small molecules for inhibitors of a human FUT enzyme involved in the synthesis of sialyl LewisX and demonstrated that our approach can be used to identify potent FUT inhibitors from compound libraries in microtiter plate format.