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Bilateral Paravertebral Blockade (T7-10) Versus Incisional Local Anesthetic Administration for Pediatric Laparoscopic Cholecystectomy: A Prospective, Randomized Clinical Study

Visoiu, Mihaela MD*; Cassara, Antonio MD*; Yang, Charles Inshik MD

doi: 10.1213/ANE.0000000000000545
Pediatric Anesthesiology: Research Report

BACKGROUND: Single-injection paravertebral nerve blocks (PVBs) provide effective postoperative analgesia after adult laparoscopic cholecystectomy (LC). We sought to compare PVBs with local anesthetic injections at laparoscopic port sites in a pediatric population.

METHODS: Eighty-three patients (8–17 years old) scheduled for LC were randomized prospectively to 2 treatment groups: the PVB group received ropivacaine 0.5% injected in the paravertebral space and normal saline injections at laparoscopic instrument sites, and the port infiltration group received normal saline in the paravertebral space and ropivacaine 0.5% at instrument sites. Postoperative analgesia was provided with hydromorphone via patient-controlled analgesia for up to 12 hours, followed by oxycodone and hydromorphone. The total amount of analgesic, serial visual analog scale scores for pain and subject pain control satisfaction, type and characteristics of pain, and complications were recorded for 24 hours.

RESULTS: The intraoperative fentanyl requirement (ng/kg/min) was lower in the PVB group than in the port infiltration group (12.81 vs 16.57, P = 0.007). Total postoperative analgesic consumption and mean visual analog scale scores were not different between the groups. Baseline pain recorded before surgery correlated with self-reported postoperative pain scores only in the port infiltration group. The rate of complications was low and similar between groups. There was no difference in incidence of patient-reported incisional, visceral, or gas pain. Shoulder pain, however, was 49% less (95% confidence interval, 0.269–0.893) in the port infiltration group.

CONCLUSIONS: PVBs did not reduce postoperative pain associated with pediatric LC but decreased intraoperative fentanyl requirements.

Published ahead of print November 25, 2014

From the *Department of Anesthesiology, Acute Interventional Perioperative Pediatric Pain Service, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and Department of Anesthesiology, Pediatric Chronic Pain Management, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Accepted for publication September 19, 2014.

Published ahead of print November 25, 2014

Funding: The project described was supported by the National Institutes of Health through grant number UL1TR000005.

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Mihaela Visoiu, MD, Department of Anesthesiology, Children’s Hospital of Pittsburgh, Children’s Hospital Drive, 4401 Penn Ave., Pittsburgh, PA 15224. Address e-mail to visoium@upmc.edu.

Postoperative pain after laparoscopic cholecystectomy (LC) can be moderate in intensity.1 The etiology of the pain has been attributed to tissue injury, residual pneumoperitoneum, and stretching of the diaphragm with associated phrenic neuropraxia.2 Administration of local anesthetic at laparoscopic port sites and/or intraperitoneal, heated and low-pressure gas, intraperitoneal saline administration, and nitrous oxide pneumoperitoneum have been investigated in trials to reduce pain, but the clinical effectiveness of these techniques is unclear.2,3 Several regional anesthesia techniques also have been proposed as adjunctive modalities.4–12 Epidural10 and intrathecal analgesia11 are effective but deemed excessively invasive in the context of minimally invasive surgery. Studies in which authors have used transversus abdominis plane blocks have been conflicting.4,5,7,8,13 Paravertebral nerve blocks (PVBs) are proven to reduce pain in adults after LC.6,9

The efficacy of PVBs for pain control in pediatric patients after LC has not been assessed. We sought to compare the effectiveness of PVBs with local anesthetic injections at laparoscopic port sites. The primary aim was total consumption of hydromorphone patient-controlled analgesia (PCA). The secondary outcomes were analgesic consumption during the intraoperative period, 0 to 24 hours, pain intensity and satisfaction scores, multimodal analgesia complications, and the characteristics of postoperative pain. We hypothesize that PVBs would offer improved pain management compared with port-site injections.

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METHODS

After receiving approval from the University of Pittsburgh IRB, we recruited and enrolled 84 pediatric subjects in this study after written parental consent was obtained. The study was registered at www.clinicaltrials.gov (NCT01380834) on June 2011. Enrollment occurred from November 2010 to May 2013 at the Children’s Hospital of the University of Pittsburgh Medical Center. Inclusion criteria consisted of (1) age 8 to 17 years, (2) ASA physical status I–III, (3) scheduled for elective LC, (4) overnight admission, (5) weight >30 kg, (6) ability to self-administer opioid via PCA, and (7) complete postoperative questionnaires. Exclusion criteria included body mass index (BMI) ≥36, diagnosis of sickle cell disease, chronic abdominal pain, acute cholecystitis, pancreatitis, or preoperative daily opiate use. Subjects with a positive pregnancy test, vertebral anomalies, scoliosis, coagulopathy, local infection at planned injection sites, allergy to medications used in study, or receiving anticoagulation medication also were excluded. The principal investigator performed all PVBs.

When the patient arrived at the same-day surgery unit, the subject was asked to rate pain on a numeric rating scale from 0 to 10, 0 being no pain and 10 the worst imaginable pain. Preoperative oral sedation with midazolam 0.5 mg/kg, up to 20 mg was made available.

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Intraoperative Study Protocol

The pharmacy performed the randomization using a computer-generated random number table. The study medications (ropivacaine 0.5% or normal saline) were labeled as study drug and released in 10 identical syringes.

In the operating room, an inhaled or IV induction was performed. If the subject did not receive any premedication, midazolam 0.1 mg/kg, maximum 4 mg, was administered. Fentanyl 1 μg/kg, up to 50 μg, lidocaine 1 mg/kg, and propofol followed by rocuronium were administered to facilitate endotracheal intubation. The subject’s lungs were ventilated with a mixture of oxygen, air, and sevoflurane to maintain end-tidal CO2 <40 mm Hg and expiratory end-tidal sevoflurane at 2 minimal alveolar concentration. A Bispectral Index monitor (Aspect Medical System, Inc., Norwood, MA) was used to monitor hypnosis, and the values were maintained between 40 and 60. Midazolam 1 mg was administered for a level greater than 60. Fentanyl 1 μg/kg, up to 50 μg, was injected for any increase in arterial blood pressure and/or heart rate >20% from baseline. All subjects received ondansetron IV 0.1 mg/kg, up to 4 mg, at the end of surgery.

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PVB Injections Protocol

After tracheal intubation, the patient was placed in lateral position. Bilateral T7-T8, T8-T9, and T9-T10 paravertebral spaces were injected under sterile condition. A 22-gauge Tuohy needle (3.15 inch; B. Braun Medical Inc., Bethlehem, PA) was inserted through paravertebral muscle until the transverse process was encountered. A loss-of-resistance syringe (Perifix®, 8 mL, plastic Luer Slip; B. Braun Medical Inc.) filled with saline was connected to the needle. The needle was withdrawn a few centimeters and directed caudally (T7, T9) under the transverse process and cranially (T9). The needle was advanced until a loss of resistance was met, and 0.1 mL/kg (maximum 5 mL) of study drug was injected into each paravertebral space.

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Protocol for Port Infiltrations

At the start of surgery, the surgeon infiltrated 0.1 mL/kg (maximum 5 mL) of study drug in the skin, subcutaneous tissue, and muscle fascia at each of the 4 laparoscopic ports. On the basis of randomization, the PVB group received 6 injections with ropivacaine 0.5%, 0.1 mL/kg/level, maximum 5 mL/level, and 4 injections of normal saline, 0.1 mL/kg/level, maximum 5 mL/level laparoscopic port sites. The port infiltration group received 6 injections in the PVB space with normal saline, 0.1 mL/kg/level, maximum 5 mL/level, and 4 injections at laparoscopic instrument sites with ropivacaine 0.5%, 0.1 mL/kg/port, maximum 5 mL/port. The subject and all members of care team, except the pharmacist, were blinded to group allocation.

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Postoperative Study Protocol

A PCA (CADD-Prizm® PCSII; Smith Medical MD, Inc., St. Paul, MN) hydromorphone with patient demand (3 μg/kg every 8 minutes) and clinician options (5 μg/kg every 30 minutes) was started as soon the subject arrived in the postanesthesia care unit and discontinued 12 hours after PVB injections. During the subsequent 12 hours, the analgesic protocol included oxycodone, 0.1 mg/kg as needed for pain, every 4 hours and hydromorphone IV, 5 μg/kg as needed for pain, every 1 hour. Ondansetron IV was available as needed for nausea/emesis, and diphenhydramine IV was available as needed for itching.

The total amounts of fentanyl (μg/kg) during surgery and postoperative PCA hydromorphone (μg/kg), rescue hydromorphone (μg/kg), and oxycodone (mg/kg) were recorded. For the final statistical analysis, to account for variable anesthesia times, fentanyl and hydromorphone PCA dose was calculated to ng/kg/min, and the total of opioid administered was converted to morphine equivalency of opioids (ME).

During the postoperative period, the subjects were asked to complete a questionnaire for abdominal pain severity using 100-mm visual analog scale (VAS), with 0 being no pain and 100 the worst imaginable pain, and to identify the pain location using a diagram. These questionnaires were repeated at 4, 8, 12, 18, and 24 hours after the PVB injections. If the subject was discharged before 24 hours, the final questionnaire was completed at the time of discharge. Pain at the incision sites was designated as incisional. Pain deep inside of abdomen and localized in right upper quadrant was categorized as visceral. Diffuse abdominal pain, difficult to localize, or resembling previous episodes of gas pain was classified as gas pain. Shoulder pain was defined as pain in one or both shoulders. On the final questionnaire, the subjects were asked about potential side effects attributable to opioid administration (nausea, emesis, itching), and the sites for PVB injections were inspected for bruising and tenderness. The subjects were asked to score their pain control satisfaction using a VAS scale. The nurse taking care of the subject or one of the investigators administered the questionnaires. The subjects’ charts were reviewed for any additional complications from opioid administration and regional anesthesia.

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Statistical Analysis

The target sample size initially was calculated using the primary outcome of total hydromorphone PCA consumption, with the assumption that the hydromorphone requirement would be 25% less in the PVB group than in port infiltration group. Assuming a power of 80%, a level of significance of 0.05, 19 subjects were required in each group. When we estimated the sample size using VAS scores to detect a difference in pain scores of 20 and assuming an average VAS pain score of 50 in the port infiltration group and a SD of 26, 42 subjects were required in each group. We elected to recruit a sufficient sample size to satisfy both clinical outcomes of interest and hence targeted a total sample size of 84.

Descriptive statistics were summarized as frequencies (%) for categorical data or as mean ± SD or median and interquartile range for normally or non-normally distributed continuous data, as appropriate. Examination of normal distribution assumption for continuous data was determined by q-q plots and histograms. Two-sample t test or Wilcoxon-Mann-Whitney U test was performed to determine differences between groups for normally or non-normally distributed continuous data, respectively. Pearson χ2 or Fisher exact test, as appropriate, was used to compare the frequency distribution of categorical variables between the groups. Separate linear mixed-effects models were used to examine whether groups were associated with VAS pain scores or ME measures. SAS procedure MIXED was used for modeling the main effects of group and time, and group by time interactions, and to account for within-subject correlation. One between-subjects factor (group) and 1 within-subjects factor (time) and their interaction were defined as fixed effects and the subject as random effect. Analyses also were adjusted by pain before surgery and shoulder pain. Examination of normal distribution assumption for residuals was determined by q-q plots and histograms. The SAS procedure GENMOD was used to fit a generalized linear model using the binomial distribution to examine whether ME was associated with shoulder pain and to account for within-subject correlation. Analyses also were adjusted by pain before surgery and robotic assistance. After inspecting the correlation within subjects, a compound symmetry structure was assumed. For significant effects, the Holm method was used for post hoc comparisons to determine the nature of the effects. Adjusted P values for post hoc comparisons were presented. All statistical analyses were 2-sided, and the significance level was set at 0.05. Data were analyzed using PASW statistics 21.0 (released August 14, 2012; SPSS Inc., Chicago, IL) and SAS (version 9.3; SAS Institute, Cary, NC).

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RESULTS

Data from 83 subjects, 41 subjects from the PVB group and 42 subjects from the port infiltration group, were included in the final analysis (Fig. 1). There were no differences in baseline characteristics between the treatment groups, except that more subjects in the PVB group underwent robotic-assisted LC (P =0.030) (Table 1).

Table 1

Table 1

Figure 1

Figure 1

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Opioid Consumption

The amount of fentanyl (ng/kg/min) administered during general anesthesia was less in the PVB group (12.81, SD ±7.73) than in the port infiltration group (16.57, SD ±7.50) (P = 0.007). Postoperatively, the total hydromorphone PCA requirement was not different (P = 0.549) although the amount of PCA hydromorphone consumption at 8 to 12 hours was greater in the PVB group (P = 0.040) than in the port infiltration group. There was no statistically significant difference in other opioid consumption (Table 2).

Table 2

Table 2

Linear mixed-effects model analysis of ME over time showed a significant main effect for time only (P < 0.0001). ME consumption decreased over time for both groups until 8 hours, but then consistent with the hydromorphone PCA results, ME increased for the PVB group but not for the port infiltration group. After 12 hours, both groups used less medication (Fig. 2).

Figure 2

Figure 2

The subjects were further evaluated by the presence of shoulder pain: PVB and no shoulder pain, PVB and shoulder pain, port infiltration and no shoulder pain, and port infiltration and shoulder pain. In the PVB group, patients who developed shoulder pain self-administered more hydromorphone PCA (ng/kg/min) between 4 and 8 hours (P = 0.028) and during the first 8 hours (P = 0.035). This relation was not seen in the port infiltration group (Table 3).

Table 3

Table 3

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Pain Scores and Satisfaction Scores

There was no statistically significant difference in VAS pain scores at hours 4 (P = 0.537), 8 (P = 0.165), 12 (P = 0.217), or 18 (P = 0.299) after the administration of local anesthetic. Pain scores at 24 hours’ discharge time were greater in the PVB group (42.18, SD ±28.73) compared with the port infiltration group (29.98, SD ±25.91, P = 0.045). There was no statistically significant difference in the mean pain scores in the first 12 hours (P = 0.333) and overall pain scores (P = 0.196). There was, however, no statistically significant difference in the mean subject satisfaction scores (PVB group, 81.66, SD ±16.91; port infiltration group, 83.83, SD ±19.97 [P = 0.594]).

Linear mixed-effects model analysis of VAS pain scores showed that the between-group effect was not significant (P = 0.280) and that there was no significant time effect (P = 0.906) (Fig. 3, A). We then examined the relationship between pain just before surgery (preoperative pain) and pain after surgery. The subjects were subdivided into 4 groups: PVB with no preoperative pain (23 subjects), PVB with preoperative pain (18 subjects), port infiltration with no preoperative pain (27 subjects), and port infiltration with preoperative pain (15 subjects). There was no significant time effect (P = 0.333), but the between-group effect was significant (P = 0.002) (Fig. 3, B).

Figure 3

Figure 3

At hours 4, 8, 12, and 24, the mean pain scores were greater in the port infiltration group for the subjects who reported preoperative pain compared with the subjects who did not have preoperative pain. This relation was not seen in the PVB group (Table 4).

Table 4

Table 4

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Pain Types

There was no difference in incisional (P = 0.555), visceral (P = 0.229), or gas pain (P = 0.353) between the groups (Table 5). More subjects reported shoulder pain in the PVB group (32; 78.05%) than in the port infiltration group (24; 57.14%) (P = 0.042). There was no difference in subjects’ age (P = 0.243), sex (P = 0.131), BMI (P = 0.943), anesthesia (P = 0.095), and surgical time (P = 0.741) between those who had or had no shoulder pain.

Table 5

Table 5

Model analysis showed that ME (P = 0.722) and time (P = 0.409) were not associated with shoulder pain, but the incidence of shoulder pain was significantly different between the PVB and the port infiltration groups (P = 0.022). The odds of having shoulder pain were 0.490 (95% confidence interval, 0.269–0.893) lower for the port infiltration group than for the PVB group.

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Local Anesthetic Administration

The total amount of ropivacaine administered was 2.35 mg/kg (SD ±0.51) in the PVB group and 1.61 mg/kg (SD ±0.34) in the port infiltration group (P < 0.001).

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Complications

Four hundred ninety-eight single injections were performed in the PVB space with no serious complications (pleural puncture and/or pneumothorax). Four subjects (3 subjects in the PVB group and 1 subject in the port infiltration group) complained of minimal tenderness at the paravertebral injection sites, which resolved without any intervention. During the PVB injections, 6 vascular punctures (1 subject in the PVB group and 4 subjects in the port infiltration group) were recorded, but these incidents did not result in any bruising or recognizable local anesthetic toxicity symptoms.

No episodes of respiratory depression were reported. There was no difference in incidence of nausea (P = 0.319), emesis (P = 0.881), or itching (P = 0.185). In addition, there was no difference in administration of ondansetron (mg/kg) (P = 0.552) and diphenhydramine (mg/kg) (P = 0.406) between the study groups.

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DISCUSSION

Our study is the first pediatric double-blinded prospective study in which we compared PVBs with incisional local anesthetic administration for postoperative pain control after LC. To ensure a reliable spread of medication, to decrease the risk of epidural spread and PVBs failure,14 we chose to perform 6 separate PVB injections. The primary results of our study differ from a previously published series in adults.6,9 Although we document a decrease in intraoperative use of fentanyl in the PVB group, we did not find any differences in quantitative or qualitative measures of postoperative pain. The fentanyl administered was statistically different, but a statistically significant difference may translate poorly to an actual benefit for the patient.

In the PVB group, there was an increase in hydromorphone PCA use 8 hours after the blocks, with several PVB subjects reporting an increase in pain 6 to 8 hours after the blocks. We had anticipated that the PVB analgesic effect would last 12 hours after local anesthetic injection9,15; however, in our pediatric population, the duration of paravertebral analgesia appeared to be shorter (6–8 hours).

In both groups, VAS pain scores were similar and did not change, despite a decrease in pain medication consumption over time. We found that the port infiltration group subjects with pain immediately before surgery reported more pain than subjects with no pain before surgery, but we cannot explain why we did not find the same relation in the PVB group.

The incidence of shoulder pain in our study was 67%. The reported incidence after adult LC is 30% to 40%. Shoulder pain is attributed to peritoneal stretching and diaphragmatic irritation.2 It can contribute to morbidity by increasing analgesic requirements postoperatively. We did not find any relation among surgery duration, BMI, overall opioid consumption, and shoulder pain, but in the PVB group, opioid consumption at 8 hours was less for the subjects with no shoulder pain. This may be a relative benefit of PVBs in subjects with no shoulder pain. Shoulder pain was more common in the PVB group. Both groups underwent injections in the paravertebral space and thus, we do not suspect a cause and effect relationship between PVBs and shoulder pain. High insufflation pressure has been associated with more postoperative pain.16 Children may be more susceptible to increased pressures because their diaphragms are thinner and thus may stretch more during standard insufflations.

In an attempt to ensure an adequate blinding of the study, maximizing the validity of the results, and to control for a placebo effect from the needle insertion per se, both groups received a therapeutic intervention (local anesthetic administration in the paravertebral space or at the instrument sites) and an “invasive” placebo intervention (saline administration in the paravertebral space or at the instrument sites). We felt that the lack of an invasive placebo would invalidate the study findings.

Invasive placebo is not without risks. We took all measures to ensure patient safety by performing the paravertebral techniques using only very well-trained faculty. The authors had not mastered pediatric paravertebral ultrasound technique when this study was designed, and therefore, this technique was not used. Normal saline solution was used to confirm the needle in the PVB space. A vessel injury from prevertebral muscle and/or paravertebral space was noted in both groups but did not result in any complications. The study drug was injected only after the needle was confirmed to not be in the blood vessel. None of the patients had any complications such us pneumothorax and/or pleural puncture. Mild tenderness at the PVB injection sites was reported in both groups but was self-resolving and did not require any interventions. Placing a dressing over the PVB needle insertion sites of both groups could have compromised double blinding and the validity of results.

There are several limitations to our study. Despite achieving a recruitment target for our study, we did not find a difference in total PCA hydromorphone consumption. The SD was much greater than anticipated, and an adequately powered study based on our findings would not be feasible.

The majority of subjects enrolled were adolescents (mean 13.4 years, SD ±2.2); previous studies have reported that pain assessment and management are difficult in hospitalized adolescents (11–18 years).17 Under these circumstances, we elected to use hydromorphone PCA consumption at 12 hours as our primary outcome. After PCA was discontinued, pain scores did not change much, but the amount of opioid administered decreased significantly, which raises the possibility that our subjects may have used the PCA demand option not only for incisional or visceral pain but also dosed in an effort to hasten ambulation, to relieve anxiety, or to improve their mood.

This study did not collect any information about psychosocial factors such as subjects’ catastrophizing attention to pain, pain behavior, anxiety, depression, or mood level. These variables influence pain scores and the decision regarding self-administration of pain medication and thereby confounded our results.18–21

Pain scores collected were specific to abdominal pain and not documented for specific shoulder pain. There were some subjects who complained more of shoulder pain than incisional, visceral, or gas pain.

We did not enroll any subjects with chronic abdominal pain, but in several cases the removal of the gallbladder did not lead to resolution of abdominal pain. These subjects may require long-term multidisciplinary interventions.

In conclusion, PVBs decreased intraoperative fentanyl consumption but were not superior to port site injections with local anesthetic for pain control after pediatric LC. Duration of analgesia after PVBs in our study was shorter than expected. Pain before surgery can influence self-reported postoperative pain scores. In this context, the analysis of pain medication consumption and postoperative pain scores should be complemented by knowledge of subjects’ catastrophizing thoughts about pain, depression, anxiety, and mood level. Shoulder pain was a potential confounding variable, unlikely to be impacted by either treatment strategies. Novel surgical strategies to prevent shoulder pain and associated opioid use should be encouraged.

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ACKNOWLEDGMENTS

The authors thank Barbara W. Brandom, MD, Professor of Anesthesiology Children’s Hospital, University of Pittsburgh Medical Center, and Jacques E. Chelly, MD, Professor and Vice Chairman of Clinical Research for the Department of Anesthesiology, University of Pittsburgh Medical Center Presbyterian–Shadyside Hospitals Aiken Medical Building, for their indispensable advice in preparation of the manuscript. We thank George K. Gittes, MD, Chair of Pediatric Surgery, Surgery-in Chief, Division of Pediatric Surgery, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center, and R. Cartland Burns, MD, Associate Professor of Surgery, Division Chief, Division of General Surgery, Department of Surgery, Nemours Children’s Hospital in Orlando, Florida, for their support with this study. We express our gratitude to the surgeons, anesthesiologists, and pharmacists who supported this project and nurses who helped to collect the questionnaires. We thank Bedda Rosario, PhD, from the University of Pittsburgh for statistical analysis on this project. We also acknowledge Michael C. Young, technical manager, University of Pittsburgh, NAMHR of MHAUS, and Lendi Joy, Research Assistant, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center, who assisted with statistical analysis.

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DISCLOSURES

Name: Mihaela Visoiu, MD.

Contribution: This author designed the study, conducted the study, collected and analyzed the data, and wrote the manuscript.

Attestation: Mihaela Visoiu has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study file.

Name: Antonio Cassara, MD.

Contribution: This author helped conduct the study, collected the data, and helped write the manuscript.

Attestation: Antonio Cassara approved the final manuscript.

Name: Charles Inshik Yang, MD.

Contribution: This author helped design the study, collected and analyzed the data, and helped write the manuscript.

Attestation: Charles Inshik Yang approved the final manuscript.

This manuscript was handled by: James A. DiNardo, MD.

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