Background: Lymphedema is a progressive, debilitating disease that may affect up to 250 million individuals worldwide. Complex decongestive therapy (CDT) remains the first line of treatment for lymphedema, and surgical treatment currently has no formally established role. In recent years, lymphovenous bypass (LVB) has emerged as a potentially efficacious intervention to improve patients' objective and subjective measures of lymphedema. Despite this promise, there are few evidence-based recommendations to inform the adoption of the practice.

Methods: A narrative review of the present literature on LVB was performed through a query of records using various combinations of Medical Subject Heading (MeSH) terms and keywords such as “lymphatic vessels,” “lymphedema,” “breast cancer lymphedema,” “surgical anastomosis,” “lymphovenous bypass,” “lymphovenous anastomosis.”  The articles were assessed for 1) bibliometric characteristics, 2) preoperative evaluation, 2) operative techniques, 3) postoperative regimens, and 4) outcome measures. 

Results: The sixty-year evolution of LVB has transformed rapidly in response to technological advances in the last two decades. The geographically distributed investigation of these surgical innovations has prompted a fragmentation of LVB practice. As original research outpaces literature review, there needs to be more consistency in terminology, perioperative practices, and evaluation of outcomes of LVB, which challenge systematic analysis. The systematic reviews to date emphasize the ability of LVB to improve objective measures such as limb circumference. Still, the inconsistent use of subjective measures limits our appreciation of the collective improvement in patient-reported outcomes. Moreover, there are a limited number of accepted methods for patient selection, preoperative evaluation, and surgical planning, with many surgical techniques employed.

Conclusion: The unifying principles and scientific evidence must be clarified to guide an overarching consensus before the widespread adoption of LVB. This article aims to synthesize recommendations and current institutional preferences concerning the research and clinical applications of LVB. The collaboration and continued refining of these practices will be necessary to establish the role of LVB in the treatment and prevention of lymphedema.

Lymphedema is a progressive, debilitating disease that may affect up to 250 million individuals worldwide [1]. In the industrialized world, secondary lymphedema often develops as a sequela of surgery, radiation, and chemotherapy in cancer treatment [2-6]. Inflammation due to surgery or chemotherapy can induce exudation of lymphatic free fatty acids and promote adipogenesis [4,7-9]. Synergistically, radiotherapy causes direct DNA damage and the release of reactive oxygen species that promote time-dependent degeneration [10-12]. The associated fibrosis and adipogenesis contribute to afterload-mediated lymphatic remodeling and dysfunction like hypertensive cardiomyopathy [4,13-17]. The disease is generally progressive, hastened by obesity, and results in reduced quality of life for up to 10 years [18].

Complex decongestive therapy (CDT) is the standard approach to lymphedema management, but routine manual drainage and compression offer limited efficacy while carrying an immense treatment burden with inconsistent insurance coverage [19-24].

The rising survivorship may predict increases in breast cancer-related lymphedema, and surgical innovations may offer solutions for preventing or mitigating the morbidity of this condition. Lymphovenous bypass is a physiological intervention that ideally prevents lymphedema progression by increasing collateral lymphatic outflow. Today, the advances in imaging and supermicrosurgical LVB confer an average decrease of 4.1 cm in limb volume and improve the quality-of-life measures in 57-100% of patients [25-30].

Despite scientific evidence that LVB can improve subjective and objective outcomes of lymphedema beyond CDT, the marked heterogeneity of practice limits the widespread adoption.6,19,20,27-42 This narrative review aims to provide an overview of current LVB research, perioperative practices, and outcome measures to highlight essential gaps in the distributed investigation of LVB, which warrant further study and consensus.

Study Design 

A literature search through December 2022 was performed across PubMed, the Web of Science, and Grey literature. A list of predetermined Medical Subject Heading (MeSH) search terms and keywords were employed, including but not limited to various combinations of the following: “lymphatic vessels,” “lymphedema,” “breast cancer lymphedema,” “surgical anastomosis,” “lymphovenous bypass,” “lymphovenous anastomosis” and the Boolean operators “AND” and “OR,” disregarding results for non-English language.  Following record screening, the remaining studies then underwent full-text review. No restrictions were set on the year of publication, country of origin, or study size. This review's inclusion depended on predefined inclusion and exclusion criteria to select original and review articles on lymphovenous bypass. Studies assessing all physiologic lymphedema surgery were included only if outcomes of interest were stratified by procedure to understand the specific role of LVB better. Articles describing other surgical interventions, such as vascularized lymph node transfer or non-physiologic lymphatic surgery without cases of LVB, were also excluded. Full-text studies were included in this narrative review if they reported on the outcomes of interest. The articles were assessed for 1) bibliometric characteristics, 2) preoperative evaluation, 2) operative techniques, 3) postoperative regimens, and 4) outcome measures. Bibliometric data included information related to the terminology used, research era, and study location. Preoperative evaluation included data related to diagnosis and imaging. Operative techniques included data about instruments, vessel selection, bypass methods, and surgical training. The primary outcomes included clinical and patient-reported outcomes.

LVB Research and Nomenclature

The composite field of lymphedema research expanded within the last two decades (87.7%), of which surgery was the second most researched topic.6 Today, the leaders of lymphedema research span Australia, Belgium, China, Germany, Italy, Japan, the United Kingdom, the United States, and Taiwan.6 A recent bibliometric analysis of lymphedema research between 1900-2023 revealed that Japan had contributed the largest quantity of papers related to “lymphovenous anastomosis” and “microsurgery” (n=73 and 41 publications/year). The second most productive country for “lymphovenous anastomosis” was the United States (n=46 publications/year), which was tied with Italy as the second most productive in “microsurgery” (n=21 publications/year) [6].

A search of terms related to lymphatic surgical “bypass” (n=1093 PubMed results) and “anastomosis” (n=1,614 PubMed results) reveal trending parallel investigations on this surgical concept between 1964 and 2023 (n=2862 total PubMed results). The two fields of work may reflect distinct clusters of surgical study (i.e., microsurgical bypass and supermicrosurgical anastomosis) or inconsistent terminology.25,26,43-46 Coriddi et al. suggest using the term “lymphovenous bypass,” as it more accurately describes the “establishment of a shunt” than does the word “anastomosis,” which refers to a “communication between or coalescence of blood vessels.”47 This paper will discuss LVB as a unified topic. 

Microsurgical Era (1960-1996)

The initial experimentation with LVB was facilitated by the advent of microsurgery in the 1960s, which permitted the surgical union of lymphatics to veins greater than 1 mm in diameter.48-52 These early models relied on dilated lymphatics and size-matched cutaneous veins for LVB, often impeded by 21 days postoperatively.50-55 In this era, lymphoscintigraphy was the gold-standard imaging modality for lymphedema, which necessitated ionizing radiation while offering low spatial and temporal resolution.

Supermicrosurgical Era (1997-Current)

In 1997, Koshima et al. demonstrated that surgical union of  vessels < 0>1mm).57 These efforts have coincided with reports of improved patency at one week (70%), one month (65%), and one year (56.5%) post-procedure.58-60 The advances in imaging came shortly after that in 2001 with magnetic resonance lymphangiography (MRL) with gadolinium-based contrast, which increased the precision of anatomical staging and treatment planning but was expensive, resource-intensive, and potentially impractical for perioperative use.61 Finally, in 2007, indocyanine green (ICG) lymphography combined with near-infrared imaging (near-infrared fluorescence lymphangiography, [NIRF-L]) surfaced as a practical and more affordable functional imaging modality capable of real-time lymphatic mapping to highlight location, drainage directionality, and collateral circulation.62 The lymphatic uptake of ICG in NIRF-L allowed for visualization that ultimately informed the concept of lymphatic territories (“lymphosomes”) [63 ].

Patient Selection

A lymphedema diagnosis can be determined by a change in volume measures, bioimpedance spectroscopy, a physical exam, and clinical history. Still, it may be enhanced by additional measures of lymphoscintigraphy, ultrasound, ICG fluoroscopy, or lymphography and classification systems (e.g., International Society of Lymphology staging criteria (ISL) [20,64-73].

The management of lymphedema differs by lymphedema stage and, in the surgical literature, often follows a stepwise application of CDT, LVB, and vascularized lymph node transfer (VLNT) with and without debulking surgery for less severe, partially obstructed, and severely obstructed lymphatics, respectively.27 There is a rationale to recommend LVB before VLNT as LVB is a less invasive procedure and more effective in early-stage disease [27,36,39,74-76]. A failure of conservative management is not an absolute prerequisite for physiologic surgery, and in patients with breast cancer, those with ≥ 10% volume change should be referred to specialist care [77].

Surgical Planning

Objective parameters of the abnormal lymphatic form (i.e., normal, dilated, or collaterals) or function (i.e., dermal backflow [DBF] or increased lymphatic transit time [TT]) are frequently integrated into the staging of lymphedema and are predictive of LVB outcomes. The current recommendation is to incorporate imaging-based modalities with a clinical assessment to characterize the severity of lymphedema and target surgical intervention more effectively. In cases of a nonfunctioning lymphatic system (NIRF-L +/- MRL) and pitting lymphedema, some recommend 1) intensive rehabilitation therapy followed by 2) reassessing the possibility of a reductive surgical technique [78,79]. A functioning lymphatic system (NIRF-L +/- MRL) with a good axillary status may indicate LVB. In contrast, an axilla with fibrotic tissue or signs of radiodermatitis may indicate VLNT with fibrotic release combined with distal LVB [79]. A VLNT can be combined with free tissue transfer and LVB for individuals pursuing simultaneous breast reconstruction [79,80]. 

NIRF-L, when combined with staging scales (e.g., the Koshima ICG Classification System, MD Anderson Cancer Center (MDACC) scale, and the Dermal Backflow Scale (DBS)), is considered the “gold standard” imaging modality for the diagnosis, severity staging, and surgical planning of LVB (Figure 2) [31,46,81-86]. The perioperative use of NIRF-L permits precise lymphatic mapping and is more predictive of outcomes than ISL.87,88 Adjunctive ultra-high-frequency ultrasound or “rest/stress intradermal lymphoscintigraphy” may enhance NIRF-L sensitivity [44,89-91].

MRL is more sensitive than NIRF-L and may be suitable for cases warranting a more detailed visualization of the deep lymphatic system (>2 cm deep to the skin surface) and surrounding tissue characteristics.31 The increased sensitivity can paradoxically influence inaccurate surgical planning and is often considered impractical due to the financial costs. New frontiers include high-frequency ultrasound imaging and photoacoustic imaging (PAI), both of which are praised for their sensitivity and, in combination with clinical presentation, have the potential to aid in the expansion of LVB indications [31,92,93].

Figure 1. Overview of lymphatic and venous vasculature frequently used in LVB. The caliber of lymphatics varies in the published literature, although they have been categorized into initial lymphatics (0.01-0.06 mm), pre-collector (0.035–0.150 mm), and collector lymphatics (0.200 mm) [182,183]. Thus, we illustrated a collector lymphatic as the relevant structure for LVB. (A) Collector lymphatics have tight “zipper-like” junctions, specialized muscle cells, and valves that coordinate directional lymph flow via suction-derived diastolic filling [3,15,172]. (B) The cutaneous vessels used in LVB generally include valved subdermal venules (0.3-0.6mm) or large cutaneous veins (>1mm).57 The microcirculatory venules and veins vary according to their ultrastructure and anatomical location, and a venule with sparse smooth muscle cells is illustrated for generalizability [101,184,185].

Figure 2. Patient selection and preoperative evaluation. Illustration of Koshima ICG lymphedema classification system [98]. (A) Stage 0: “Normal superficial lymphatic vessels appear as a “linear” pattern with no dermal backflow” (B) Stage 1: “Lymphatic vessels appear dilated and torturous with areas of ICG accumulation as a “splash” pattern” (C) Stage 2: “Contracted lymphatic vessels with loss of intraluminal diameter and thickening of the smooth muscle cell coverage. Lymphatic vessels are disrupted, causing increased areas of ICG accumulation as a “stardust” pattern” (D) Stage 3: “No lymphatic vessels can be seen and there is ICG accumulation as a “diffuse” pattern”[98].

Instruments

The preferred instruments for LVB vary and include either supermicrosurgical forceps (0.05 mm tips) or standard microsurgical forceps (0.3 mm). Some consider supermicrosurgical forceps too malleable to avoid damaging the lumen of the lymphatics. Titanium supermicrosurgical instruments and surgical scissors are generally employed.94

Selection of Target Lymphatics 

Figure 3 illustrates the step-wise process for selecting target vessels. The lymphatic targets appropriate for bypass must be functional as there is evidence of little to no therapeutic benefit of performing LVB with sclerotic lymphatic vessels. The use of LVB has demonstrated objective and subjective improvement in the lower extremity (objective 46.7-100%, subjective 84-100%) and upper extremity (objective 0-100%, subjective 50-100%) lymphedema.28,29 Functional imaging (i.e., NIRF-L) is recommended for reverse lymphatic mapping. The functional vessels draining the affected distal extremity will appear bright under NIRF-L due to their uptake of ICG (1-2 mg) injected intradermally into the alternating web spaces of the impacted hand or foot.95,96 The fluorescence pattern will demonstrate the disease severity. Incisions are generally guided by dermal backflow (NIRF-L findings) and placed according to the mapped functional lymphatics.36,84,97,98  There is no consensus on the preferred incision length. Still, using the AccuVein system (AccuVein Inc.) in conjunction with NIRF-L, Mihara et al. performed the procedure through a 2-mm incision.45 Isosulfan blue (Lymphazurin; United States Surgical Corp., Norwalk, CT) or methylene blue (American Reagent, Shirley, NY) is helpful intraoperatively, as it allows for gross visualization of lymphatic patency and function (Figure 3). A functional lymphatic is thus frequently defined as both ICG-positive and flow-positive. 

Figure A

Figure B

Figure 3: Selection of lymphatic and venous targets. (A) The lymphatic territories (lymphosomes) can be visualized with ICG. Lymphosomes superior to inferior 1) temporal, purple; 2) occipital, blue; 3) mental, tan; 4) supraclavicular, pink; 5) subscapular, not pictured; 6) axillary, dark teal; 7) pectoral, orange; 8) superior inguinal, red; 9) lateral inguinal, salmon; 10) inferior inguinal, magenta; 11) popliteal, not pictured. [illustration of lymphosomes adapted from Suami et al.]186 (B) Pre-incision selection of target vessels will depend on the location of the obstruction and the presence of fluorescent lymphatics and neighboring veins. The incision should be placed over a junction between a lymphatic and vein (X and overlying circle). The incision can be made perpendicular to the lymphatic. Selecting several possible sites for incision is ideal (C) lymphatic and vein in preparation for LVB.

The fibrotic and pressure-overloaded lymphatic in the diseased state will dilate and exhibit ineffective lymphatic pumping.4,7,15 In a recent analysis of 1048 lymphatic vessels, Yang et al. extrapolated that 0.5 mm (lymphatic vessel0.5) represented the threshold for lymphatic function, with calibers ≤ 0.5 mm associated with an adequate function (defined as ICG and flow positive) and postoperative volume reductions [99]. 

Selection of Recipient Veins/Venules 

The pressure gradient, tension, and flow dynamics of the recipient vein (RV) are paramount for a successful bypass.100 An algorithmic approach to venule or venous selection can be based on [1] caliber match, [2] location, and [3] the presence of backflow [100,101]. The original framework considered small RV (≤ 0.4-0.5mm) superior to larger RV in minimizing backflow. This theory potentially contradicts the traditional teaching that, in the supine position, the superior vena cava exhibits the lowest venous pressure as it drains into the right atrium (0-3mmHg) and is precipitously lowered by negative thoracic pressure during inspiration and by gravitational pull when standing [101,102]. Conversely, peripheral venules have higher intraluminal pressures due to an increased net cross-sectional area and relative gravitational influences (hand: +35 mm Hg, foot: +90 mm Hg).103 

One study evaluating RV of 1,000 LVBs of similar lymphatic characteristics classified RV according to Visconti flow dynamic classifications, which demonstrated that the smallest RV  (≤ 0.4mm) were significantly associated with the least favorable outcomes of backflow and slack compared with medium (0.5-0.9mm) and large (≥ 1mm) RV.100 Matching the caliber of RV and lymphatics while minimizing LVB tension was informative on the final LVB configuration's influence on the outcomes. A physiologic evidence-based algorithm for venous choice is provided in the referenced work [101]

LVB Technique: Configuration

Table 1 depicts the variety of available techniques for LVB from the published literature [43,104-106]. The photographs in Figure 4 demonstrate the practical application of a sequence of methods. The relevance of alternative strategies is primarily addressed in the original papers and institutional care algorithms [94,107-109]. The first described approaches to LVB drew inspiration from microsurgical anastomosis of blood vessels and included end-to-end (E-E) and end-to-side (E-S) configurations [94,110]. However, the postoperative histological evaluation in that era demonstrated that E-E was associated with slight narrowing at the LVB site and that E-S LVB was more often disrupted due to inflammatory changes [51,101]. E-E has remained the most prominent technique across institutions, with authors citing the relative ease of use in caliber matching and improved resistance to venous backflow compared to E-S. 

Table 1. Surgical Techniques for Lymphovenous Bypass. Depicts information and illustrations of LVB techniques as described in the published literature. The list is not comprehensive, and more options for LVB exist. Configurations are described by the direction of the union and include end-to-end (E-E), end-to-side (E-S), side-to-end (S-E), and side-to-side (S-S). Ratios of lymphatics: recipient veins (RV) comprise the number of individual, native lymphatics included in the LVB; lymphatics transected and employed using the proximal and distal ends were counted as one lymphatic. Ratios of 2:1 are described as λ-shaped, but the technique is described in the published literature as involving two ends of a transected lymphatic rather than a method of 2:1 LVB. Because procedures involving RV outlets <0>0.8, the procedure was marked with a “+/-.” Procedures that have been applied in the setting of immediate lymphatic reconstruction (ILR) were marked with a “+.” Illustrations are basic representations of the configurations drawn according to the procedural descriptions or images in the referenced articles. Lymphatics, valves, and direction of lymphatic flow (arrows) are depicted in green. RV and direction of flow (arrows) are displayed in dark blue; venous valves are in pink. The directionality of lymphatic flow was based on the orientation described in the technical articles, as lymphatics and RV have directional valves supporting flow in a distal to proximal manner. If the proximal or distal end of the lymphatic or vein was not specified, the directionality was depicted in the anatomical fashion, which would theoretically optimize flow. Modifications to the described approaches are listed with the procedures they are reportedly applied to.

                                                                                                                                  Figure 4A

                                                                                                                                     Figure 4B

                                                                                                                                       Figure 4C

                                                                                                                                   Figure 4D

Figure 4. Operative techniques in LVB. (A) Transection of the target lymphatic area should demonstrate lymphatic function. This is facilitated by subcutaneously injecting Isosulfan blue (Lymphazurin; United States Surgical Corp., Norwalk, CT) or methylene blue (American Reagent, Shirley, NY) along the fluorescent lymphatic pathway. (B) Intravascular stenting (IVaS) can be performed with nylon sutures prior to LVB. (D) an implantation technique implants the lymphatic into the venous lumen, using a stitch to connect lymphatic adventitia to venous intima. (E) The success of the bypass can be determined by direct visualization of the unidirectional flow of fluorescence from lymphatic into the recipient vein (distal to proximal) under microscopy.

In 2022, Bianchi et al. further noted that E-E had superior flow characteristics compared to side-to-end (S-E) and side-to-side (S-S). These findings contrast numerous reports corroborating S-E as superior to E-E, particularly in more advanced lymphedema [111,112]. However, Kwon et al.’s results favoring S-E incorporated significantly higher ratios of lymphatics: RV in the S-E group than in the E-E group, possibly confounding their results. Yamamoto et al. reported that S-E and S-S unions outperformed E-S, often resulting in venous-lymphatic reflux and thrombosis [113]. The authors cited that bidirectional drainage is a favorable dynamic, which remains controversial [101,113,114]. 

A myriad of publications describes combinations and variations of these configurations, including 

The surgical treatment of lymphedema must be combined with lifestyle interventions and postoperative compression. The most common recommendation is to avoid compression in the immediate postoperative period and instead encourage consistently elevating the affected limb though not more than 90 degrees.152,153 The patient can continue compression, lymphatic massage, and lymphedema therapy between 2-4 weeks postoperatively, taking care to avoid massaging incisions, and by one month, they can return to usual activities.152 The outcomes are improved by combining surgery with decongestive therapy, but patients often discontinue CDT postoperatively.154,155 The referrals and planning for post-ILR lymphedema surveillance are usually initiated preoperatively. The regimen after surgery consists of two weeks of decongestive therapy and activity limitations followed by a gradual return to range-of-motion exercises.34,143,146,147  In the first 24 months, patients are screened every three months by specialized physical medicine and rehabilitation physicians for the development of lymphedema via Lymphedema Index (L-Dex; Impedimed, Carlsbad, CA) bioimpedance and arm circumference measurements.156 Beyond two years, patients can be transitioned to bi-annual monitoring. Individuals with abnormal exams should be counseled to wear prescribed compression sleeves (20-30 mm Hg) during daytime hours and be instructed to return after six weeks of wear for retesting. 

The quality and quantity of lymphedema outcome measures limit the evaluation of LVB efficacy [157].  The objective measures of treatment include limb circumference and volume, which are the most comparable measures of treatment efficacy for lymphedema. Though these metrics are often criticized for being antiquated and unacceptably dynamic, the pooled effects of LVB are considered significantly efficacious in reducing limb circumference or volume [27,158]. Objectively, LVB is associated with a pooled decrease in cutaneous infections.33 Finally, ILR is demonstrated to effectively reduce the risk of lymphedema as measured by a decline in prevalence, incidence, and relative risk [5,32,34,35,38,150,159,160].

The subjective patient-reported outcomes (PROMS) are considered to “improve” after LVB, but metrics are considered too heterogeneous to compare and of universally poor methodological quality [27,30,41]. The Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) analysis suggests that the PROMS with the best methodological quality included the lymphedema life impact scale (LLIS), Lymphoedema Functioning, Disability and Health questionnaire ([Lymph-ICF]; lower-limb specific [Lymph-ICF-LL]), patient benefit index-lymphedema (PBI-L), and upper limb lymphedema 27 (ULL-27) [161-166]. 

Future Directions

Lymphatic Surgical Training

There is yet to be formalized training for supermicrosurgery, which may create additional barriers to entry. To participate in training, expert microsurgeons can engage in a “line production method” for LVB with novice microsurgeons using a microscope and loupes, respectively, as these are demonstrated to increase the quantity and quality of LVB beyond those produced by a traditional single expert, single microscope approach [151]. Papaverine can also prevent lymphatic spasms and reduce lag between novices and experts. Training models are constantly being improved and are demonstrated to support standard microsurgical instruments in anastomosis vessels of up to 0.3mm in an average of approximately 6 minutes [118,167-170]. 

Physiologic and Biomechanical Research

The lymphatic function and contractile strength may be influenced by manipulation of the luminal size due to fibrosis or surgical technique.  Unlike blood vessels, lymphatic vessels propagate fluid synchronously, contracting reminiscent of the cardiac cycle [171]. The current understanding of the lymphatic circulatory system is that it 1) is a low velocity, low-flow system, 2) is composed of individually actively pumping lymphangions bounded by valves, 3) exhibits nonlinear flow or hysteresis, 3) collecting lymphatics exhibit Starling forces with a cyclical contraction (systole), positive transluminal pressure, and ‘suction pressure’ necessary for passive diastolic filling, and 5) is influenced by downstream, upstream, and external pressures [172]. These recently uncovered features indicate the increasing complexity of lymphatics, which may predispose an unpredictable response to surgical interventions. The modern physiologic and biomechanical evaluation of lymphedema surgery in ex-vivo and in-vivo experimentation models lags behind clinical research. Testing these surgical procedures on animal models for lymphedema could enhance the scientific logic behind various practices in LVB [173-180]. 

The scientific exploration of LVB dates back to the 1960s, during which several imaging methods were developed which permitted further surgical innovation. Over the last twenty years, LVB research has blossomed, driven by novel investigations of surgical techniques.6 The current practices of LVB are evidenced to impact patients’ lives positively, but inconsistent practices challenge the development of evidence-based guidelines and integration in treatment algorithms. Intradisciplinary standardization and high-quality comparative research are needed to inform LVB perioperative decision-making and reach a consensus [30,99,181].

Authors’ contributions

Made substantial contributions to the writing of the original draft, review and editing, visualization, and project administration, and gave final approval of the version to be published: Daisy L. Spoer, MS

Made substantial contributions to the writing via review and editing and gave final approval of the version to be published: Lauren E. Berger, BA

Made substantial contributions to the writing via review and editing and gave final approval of the version to be published: Parhom N. Towfighi, MD

Made substantial contributions to the writing via review and editing and gave final approval of the version to be published: Karen R. Li, BS

Made substantial contributions to the conception and design of the study, writing via review and editing, supervision, and gave final approval of the version to be published: Laura K. Tom, MD.

Availability of data and materials 

The data supporting this study's findings are available from the corresponding author, [L.K.T.], upon reasonable request.

Financial support and sponsorship

None.

All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate

This study was performed in line with the principles of the Declaration of Helsinki. This study was conducted with approval granted by the Georgetown-Medstar Institutional Review Board (IRB ID: STUDY00004860, 03/02/2022). All participants provided written informed consent.

Consent for publication

Participants provided written informed consent.

© The Author(s) 2022.