The risk of iatrogenic radial nerve and/or profunda brachii artery injury in anterolateral humeral plating using a 4.5 mm narrow DCP: A cadaveric study.

INTRODUCTION: Fixation of humeral shaft fractures with a plate and screws can endanger the neurovascular structure if proper care is not taken. No studies to our knowledge have studied the risk of iatrogenic radial nerve and/or profunda brachii artery (RNPBA) injury from each screw hole of a 4.5 mm narrow dynamic compression plate (narrow DCP). The purpose of this study is to evaluate the risk of RNPBA injury in anterolateral humeral plating with a 4.5 mm narrow DCP.
MATERIAL AND METHODS: 18 humeri of 9 fresh-frozen cadavers in the supine position were exposed via the anterolateral approach with 45 degrees of arm abduction. A hypothetical fracture line was marked at the midpoint of each humerus. A precontoured ten-hole 4.5mm narrow DCP was applied to the anterolateral surface of the humerus using the fracture line to position the center of the plate. All screw holes were drilled and screws inserted. The cadaver was then turned over to the prone position with 45 degrees of arm abduction, and the RNPBA exposed. The holes through in which 100% of the screw had contact with or penetrated the RNPBA were identified as dangerous screw holes, while lesser percentages of contact were defined as risky.
RESULTS: The relative distance ratios of the entire humeral length from the lateral epicondyle of the humerus to the 4th, 3rd, 2nd and 1st proximal holes were 0.64, 0.60, 0.56 and 0.52, respectively. The most dangerous screw hole was the 2nd proximal, in which all 18 screws had contacted or penetrated the nerve, followed by the risky 1st (12/18), 3rd (8/18) and 4th (2/18) holes.
CONCLUSION: In humeral shaft plating with the 4.5mm narrow DCP using the anterolateral approach, the 2nd proximal screw hole carries the highest risk of iatrogenic radial nerve and/or profunda brachii artery injury.

Introduction

In a humeral shaft fracture, the middle third of the diaphysis was the most common fracture location with the incidence of 60% [1]. The radial nerve and profunda brachii artery could have been injured during the trauma that caused the fracture, or they could be injured during the fixation from drilling the screw holes or inserting the screws [2-5], as these structures are located on the posterior aspect of the humeral shaft, crossing the humerus obliquely from the posteromedial to the posterolateral sides, but their precise location cannot be known by the surgeon performing the fixation and drilling screw holes and inserting screws [6-8]. Earlier studies have reported incidences of radial nerve injury during surgical fixation ranging from 3.57% to 18.20% [9-11].

There are two main treatment methods for a humeral shaft fracture. The first is conservative treatment with a “sugar tong splint” or “functional brace”, and the second is operative treatment with a plate or nail system [12, 13]. In mid-shaft humeral fixation, humeral shaft plating is preferred by most surgeons to humeral shaft nailing [14, 15], with some studies showing higher functional outcomes [16] and lower complication rates [17-19] when fixing with plate and screw. Some surgeons prefer to do humeral shaft plating using the anterolateral approach while some surgeons prefer the posterior approach [14]. The posterior plating is more suitable for mid- to distal shaft humerus fractures, while the anterolateral plating is more suitable for proximal to mid-shaft humerus fractures. There have been three studies comparing the anterolateral and posterior plating in humeral mid-shaft fixation [9-11], in all of which both plating had excellent outcomes in union rate, range of shoulder and elbow motions, and functional scores. The complication of iatrogenic radial nerve palsy in most studies were similar between the two locations of the plate which the incidence were 3.57–14.20% in the anterolateral plating and 16.67–18.18% using the posterior plating. In contrast, one study reported that the incidence of iatrogenic radial nerve palsy in the anterolateral approach was higher than the posterior approach. Wang et al. reported on 39 cases of iatrogenic radial nerve injury during plating, 37 cases of anterolateral plating and 2 cases of posterior plating [4].

In the anterolateral plating, the surgeon can use one of two common types of plate, the 4.5 mm narrow dynamic compression plate (narrow DCP) or the 4.5 mm narrow locking compression plate (narrow LCP) [10, 20–23]. These plates are applied to the humerus in different locations, and thus the trajectory of the screws is also different. The 4.5 narrow DCP is commonly applied at the anterolateral surface of the humerus (Fig 1) [9–11, 24], while the 4.5 mm narrow LCP can be applied at either the mid-anterior aspect (Fig 2) or the anterolateral surface [21, 25, 26]. The direction of the screws while applying the plate at the anterolateral surface is from the anterolateral aspect of the humerus to the posteromedial aspect, while the direction of the screws while applying the plate at the mid-anterior aspect of the humerus is from the mid-anterior to the mid-posterior area of the humerus. The radial nerve and profunda brachii artery run from the posteromedial to the posterolateral aspect of the humerus, and are at risk of iatrogenic injury in both anterolateral and posterior plating. When applying the plate at the anterolateral surface of the bone, earlier studies have reported a risk while drilling some screw holes and/or inserting the screws but none of these studies provided the individual risk of each hole position. When applying the plate at the posterior aspect of the humerus, earlier studies have reported a risk in the step of finding the radial nerve and profunda brachii artery as they pass across the mid-posterior aspect of the humerus before applying the plate [6-8]. A study by Apivatthakakul et al. evaluated the dangerous screw holes in mid-anterior humeral plating using the locking plate and reported that insertion of the fourth to eighth screws carried a risk of iatrogenic radial nerve injury [26]. They found that the incidences of these screws contacting or damaging the radial nerve were 22.2%, 38.9%, 50.0%, 44.4% and 16.7%, respectively. The 4.5 mm narrow DCP is one of the standard plates in anterolateral humeral shaft plating [27] because it provides good stability [28] at a lower price, and is also available in all hospitals, which are notable considerations in developing country. However, to our knowledge, there have been no studies to date evaluating the dangerous screw holes in anterolateral humeral shaft plating using the 4.5 mm narrow DCP.

Fig 1

The anterolateral surface of the humerus (green shaded area) shows the area in which the plate can be applied.

Fig 2

The mid-anterior aspect of the humerus (brown shaded area) shows the area in which the plate can be applied.

There were two purposes of this study. The first was to identify the screw holes that are most dangerous in terms of causing an inadvertent radial nerve and/or profunda brachii artery injury while drilling the holes or inserting the screws for the 4.5 mm narrow DCP plate. The second was to measure the distances between the screw tips to the radial nerve and profunda brachii artery in anterolateral humeral plating with this plate. Due to the location of the plate and direction of the screws, we hypothesized that the dangerous screw holes in humeral plating using the 4.5 mm narrow DCP would be the 1st proximal and 2nd proximal screw holes.

Material and methods

18 humeri of 9 full-body fresh-frozen cadavers, 5 males and 4 females, with a mean age at death of 60 ± 10 years, obtained from Prince of Songkla University were used for the study. This study has been approved from the Ethics Committee of Prince of Songkla University (REC 62-434-11-1). The average length of the cadavers was 166 ± 8 cm, and the average humeral lengths in the male and female cadavers were 297.25 ± 2.12 mm and 277.50 ± 1.73 mm, respectively. Each cadaver was thawed at room temperature for 12 hours before the procedures were performed.

For the procedures, each cadaver was first placed in the supine position with 45 degrees of arm abduction and full supination of the forearm. A well- experienced orthopaedic surgeon (15+ years) used the standard anterolateral approach for humeral plating with a ten-hole 4.5 mm narrow DCP. The initial skin incision was made from the tip of the coracoid process to 5 cm proximal to the flexion crease of the elbow. The deltoid muscle was retracted laterally and the pectoralis major retracted medially. The brachialis muscle was split to expose the humeral shaft. A fracture line was set at the midpoint between the tip of the greater tuberosity to the lateral epicondyle. A ten-hole 4.5 mm narrow DCP was contoured to match the anterolateral surface of the humerus, and applied at the anterolateral aspect of the humerus using the fracture line to position the center of the plate. In this step, if the deltoid insertion interfered with the plate application, the deltoid insertion was detached as little as possible to allow the application. When the plate was properly in place, the screw holes were numbered in two directions moving outward from the midpoint of the plate. The hole closest to the midpoint in the proximal humerus direction was identified as the first proximal screw hole, the next hole in that direction the second proximal screw hole, etc. until the last was identified as the fifth proximal screw hole. For the screw holes on the side toward the distal humerus, the hole closest to the midpoint in the distal direction was identified as the first distal screw hole, the next hole in that direction the second distal screw hole, etc until the last was identified as the fifth distal screw hole. The holes were then drilled and tapped and the cortical screws inserted by hand. To decrease potential bias from the drill and screw directions, a drill sleeve was positioned perpendicular to the plate and centered to the bone by the surgeon and an assistant. After the fixation, the distance from the lateral epicondyle of the humerus to the center of each screw hole was measured along the lateral border of the humeral shaft for calculation of the relative ratios with the entire humeral length (Fig 3). Finally the skin was closed layer by layer.

Fig 3

Anterior view of a right upper arm, with an imaginary fracture line at the midpoint between the tip of the greater tuberosity and the lateral epicondyle (white dotted line).

The distances were measured from the lateral epicondyle to the tip of the greater tuberosity of the humerus (entire humeral length; black arrow) and the center of each screw hole (orange arrow). The relative distance ratio of each screw hole was calculated based on the distance from the lateral epicondyle to each screw hole (orange arrow) and the entire humeral length (black arrow).

The cadaver was then turned over to the prone position with 45 degrees of arm abduction and full forearm supination. A posterior incision was made from the posterolateral corner of the acromion process to the tip of the olecranon process by an experienced (10+ years) micro-neurovascular orthopaedic surgeon. A triceps-splitting approach was done between the long head and the lateral head of the triceps and the radial nerve and profunda brachii artery exposed. In this step, only the medial and lateral borders of the radial nerve and profunda brachii artery were exposed to preserve an as near-as-normal relationship of the neurovascular structure to the bone, and the screw holes examined. The distances from the lateral epicondyle of the humerus to the proximal and distal parts of the radial nerve and profunda brachii artery were measured.

In each humerus, the screw holes from which the screw tips were in contact with or had penetrated the radial nerve and/or profunda brachii artery in all cadavers were identified as dangerous screw holes and the screw holes that had penetrated the radial nerve and/or profunda brachii artery in only some cadavers were identified as risky screw holes. The distances from the screw holes in the zone where the radial nerve and profunda brachii artery crossed the humerus to the radial nerve and profunda brachii artery in the longitudinal and closest planes were measured using a Vernier caliper with a precision of 0.001 mm (Insize, Suzhou New District, China) (Fig 4).

Fig 4

Posterior view of a right upper arm; the distances from the screw holes to the neurovascular structure were measured in the longitudinal plane (green line) and closest plane (yellow line).

To decrease measurement bias, one orthopaedic surgeon measured each distance three times, and the mean ± SD was calculated. The statistical analysis was performed using the R program and “epicalc” package (version 3.4.3; R Foundation for Statistical Computing, Vienna, Austria). Intraobserver reliability was calculated by intraclass correlation coefficients.

Results

In anterolateral humeral shaft plating with the ten-hole 4.5 mm narrow DCP, the relative distance ratios of the entire humeral length from the lateral epicondyle of the humerus to the 4th, 3rd, 2nd and 1st proximal holes were 0.64, 0.60, 0.56 and 0.52, respectively, while the relative distance ratios of the entire humeral length for the distances from the lateral epicondyle of the humerus to the proximal and distal parts of the radial nerve and profunda brachii artery were 0.65 and 0.45, respectively. The only dangerous screw hole identified in our study was the 2nd proximal screw hole, while the 4th, 3rd and 1st proximal holes were classified as ‘risky’, with incidences of iatrogenic radial nerve and/or profunda brachii artery injury of 2/18 (11.11%), 8/18 (44.44%) and 12/18 (66.67%) fixations, respectively (Fig 5).

Fig 5

Anterior view of a right upper arm, showing an imaginary fracture line at the midpoint between the tip of the greater tuberosity and the lateral epicondyle (white dotted line), indicating the risk of iatrogenic radial nerve and/or profunda brachii artery injury of each screw hole.

The average distances from the 4th, 3rd and 1st proximal screw holes to the radial nerve and profunda brachii artery in the longitudinal and closest planes are shown in Table 1. Each distance was measured three times by a single orthopaedic surgeon; the intra-observer reliability ranged from 0.83 to 0.99.

Table 1

The average distances of the ‘risky’ screw holes to the radial nerve and profunda brachii artery in the longitudinal plane and closest plane (Mean ± SD).

Screw hole	Longitudinal plane (mm.)	Closest plane (mm.)
4th proximal	29.19 ± 16.44	24.44 ± 14.63
3rd proximal	18.69 ± 15.63	15.39 ± 13.31
1st proximal	12.30 ± 5.13	10.75 ± 4.86

Discussion

Fixation of a humeral shaft fracture with a 4.5 mm narrow DCP can involve accidental injury to the radial nerve and/or profunda brachii artery because these structures pass very close to the humeral bone in an area where a drill bit or screw can potentially injure them. In our study, we found that the most dangerous screw hole was the 2nd proximal screw hole, with a relative distance ratio of 0.56, for which the surgeon must be very careful not to drill and tap the hole or insert the screw beyond the edge of the far cortex of the bone. The 4th, 3rd and 1st proximal screw holes were identified as ‘risky’ holes, with varying chances of an iatrogenic neurovascular injury from a bicortical screw.

This study had some limitations. First, the cadavers of different lengths had different humeral lengths, and real patients will of course also have different lengths of humeri. In this study, we reported the positions of the “dangerous” and “risky” screw holes that can be applied in the average patient, and we also reported the relative distance ratios of the “dangerous” and “risky” screw holes that can be applied in all sizes of humeri. Second, we tried to keep the normal relationship between the radial nerve/profunda brachii artery and the humerus by exploring only the medial and lateral borders of the radial nerve and profunda brachii artery, but in real patients the anatomical relationship between the radial nerve/profunda brachii artery and the humerus will differ to greater or lesser extents depending on the patient’s age, degree of soft tissue injury and the alignment of reduction. Third, we had no way of knowing if there had been any previous injury to the humerus of the cadavers, but cadavers with obvious lesions or deformities of the humerus were excluded. Forth, in actual humeral fractures, the distances from the plate and screws to the radial nerve and profunda brachii artery may be different from the distances in this study, depending on the degree of soft tissue injury and/or reduction alignment.

The radial nerve and profunda brachii artery cross the posterior humerus obliquely from the medial to the lateral sides [6-8]. There is a chance of iatrogenic radial nerve injury in either the anterolateral or the posterior humeral shaft plating, with incidences of between 3.57% and 18.20% [9-11]. Previous studies have reported the incidence of radial nerve palsy in the anterolateral plating was similar to the posterior plating, but significantly higher only in one study [4]. The posterior plating can endanger the radial nerve and/or profunda brachii artery by plate compression or accidental injury during surgical exposure while the anterolateral plating can injure the radial nerve and/or profunda brachii artery while drilling the screw holes and/or inserting the screws [9].

Several studies have evaluated the anatomical location of the radial nerve in relation to different landmarks such as the olecranon process, lateral epicondyle, medial epicondyle, intermuscular septum and/or acromial process [8, 29–31]. The study of Suwannaphisit et al. found that the radial nerve passed the posterior humerus from 130.00 ± 2.07 mm between the upper olecranon and the center of the radial nerve to 122.00 ± 2.33 mm between the lateral epicondyle and the lateral intermuscular septum [30]. In another study, in relation to the epicondyle, the radial nerve passed the posteromedial-to-posterolateral aspect of the humerus between 152 mm and 66 mm from the medial epicondyle [8]. Chou et al. reported the distances from the acromial process to the upper margin and lower margin were 147 ± 21 mm and 195 ± 36 mm, respectively [31]. Additionally, Natsis et al. reported a rare anatomical variation of the radial nerve at the upper humeral level involving an atypical communicating branch between the radial nerve and ulnar nerve, with an incidence was 2.3% [32]. Due to the anatomy and natural variations of the exact location the radial nerve crosses the humerus, there is always a risk of iatrogenic radial nerve injury in anterolateral plating when the screws exit the bone in the area where the radial nerve passes the posterior humerus. Using the results of our study, the surgeon can evaluate the risk of injury for each screw hole separately in their particular situation. In our study, we found that inserting the screw into the 2nd proximal screw hole, which had a relative distance ratio of 0.56, resulted in a 100% chance of iatrogenic radial nerve and/or profunda brachii artery injury. The “risky” screw holes with this plate were the 4th, 3rd and 1st proximal screw holes, for which the relative distance ratios were 0.64, 0.60 and 0.52, respectively. The results from our study were different from a previous study of Apivatthakakul et al. which reported that the incidence of screws contacting or damaging the radial nerve in the fourth to eighth screw holes of a 4.5 mm narrow LCP were 22.2%, 38.9%, 50.0%, 44.4% and 16.7%, respectively [26]. These differences could be explained by noting the different methods between our study and the Apivatthakakul et al. study, notably the types of plate used, the different directions of the drill bit and screws between a 4.5 mm narrow LCP and a DCP, and the locations and landmarks used when applying the plate.

To avoid the potential of injury with the DCP, we recommend measuring and calculating the relative distance ratios intraoperatively. Inserting a bicortical screw at the 2nd proximal screw hole can endanger the radial nerve and/or profunda brachii artery by the tip of the drill bit when drilling the screw hole, the tip of the depth gauge when measuring the length of the screw hole, the tip of the tapping device when tapping the screw hole, or the tip of the cortical screw. To avoid the risk of radial nerve and/or profunda brachii artery injury using the 4.5 mm ten-hole narrow DCP, the surgeon should drill and tap only one side of the cortex and use a unicortical screw. For the other “risky” screw holes, the surgeon should be careful in all steps of drilling the holes and inserting the screws which have a chance of iatrogenic radial nerve and/or profunda brachii artery injury.

Conclusion

In anterolateral humeral shaft plating with the 4.5 mm narrow DCP using the anterolateral approach, we found that the 2nd proximal screw hole with a relative distance ratio of 0.56 carried the highest risk of iatrogenic radial nerve and/or profunda brachii artery injury. We recommend that only a unicortical screw should be used for the 2nd proximal screw hole with the 4.5 mm narrow DCP using the anterolateral approach.

(XLSX)

Click here for additional data file.

9 Oct 2021

PONE-D-21-25577The Risk of Iatrogenic Radial Nerve and/or Profunda Brachii Artery Injury in Anterolateral Humeral Plating using a 4.5 mm Narrow DCP: A Cadaveric StudyPLOS ONE

Dear Dr. SUWANNAPHISIT,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please explain in detail why you prefer an anterolateral approach in fracture types carrying a risk of iatrogenic risk of radial nerve as well as profunda brychii artery insteasd of a dorsal approach, which provides a direct visualisation of nerve and vessels. Refer to any comment of the reviewers.

Please submit your revised manuscript by Nov 23 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Hans-Peter Simmen, M.D., Professor of Surgery

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. In the Methods section of the manuscript please ensure that you have specified the full name of the university which provided the Cadavers for the study.

3. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

4. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript.

5. Please include a copy of Table 1 which you refer to in your text on page 10.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Basically the authors have found out, that the "2nd proximal screw" is dangerous (100% hits) with other proximal screws (1/3 and 4) being risky (11-67%). The most proximal and all screws distal to the humerus' middle are not risky. Unfortunately, I was not able to open/view Table 1. The figures are all good, instructive and of good quality.

L82: Dorsal plating with direct visualization of the radial nerve is also a popular technique which needs to be mentioned. I am not so sure that most surgeons prefer anterior plating… (at least not for midshaft fractures and those located more distally)

L88-91: Why is the plate position different for DCP and LCP, respectively? Aren't they placed the same way?

L100: The authors state that the narrow 4.5 DCP is the most commonly used plate for the humerus shaft. However, no references are provided.... I strongly disagree with the authors. I do not think that is true for Europe and North America and other developed countries.

L 232 Different directions of the drill bit? In LCP the locking screws are inserted in a perpendicular manner as well. I don't see a difference here? Please explain.

I would like to have studies discussed which have investigated the anatomical variations of the radial nerve in relation to the humeral bone. This aspect is totally neglected in the discussion. Furthermore, results and complications (regarding the radial nerve and accompanying artery) of anterior humeral plating should be reviewed and discussed with the findings of your study. Only one similar study is (Apivatthakakul et al) is mentioned.

I would suggest a more thorough and critical review of the literature regarding the variation of the radial nerve and the accompanying vessels, other experimental studies and results and complications of clinical studies with anterior plating.

Reviewer #2: Line 50: "A hypothetical fracture line was marked at the midpoint of each humerus." Can you provider some data why you choose the fracture line there?

Line 79 Introduction: This part is to short. You should give some feedback information about the percentage of humerus fractures and numbers about prim. and sec. nerve damage.

Line 80: Can you make some comments about the posterior approach for plating and the percentage of nerve damage from each approach?

Line 92: re-phrase please

105-111: please rephrase this very long sentence.

Line 124: can you be more specific what "experienced means with a number of years in experience

Line 130: see comment 50

Line 154: see comment number 124:

Line 215: rephrase in a more scientific way.

Line 223: Important discussion/limitations as well is the fact, that the holes this close to the fracture, according the AO-Guidelines, are normally left empty. Please add this as a discussion point.

Line 245: I don’t fully see the connection between this two studies. And according to the AO cerclage wiring are not recommended at the humerus shaft.

Line 256: What about using a different approach like the posterior one? There are studies out that this approach when used primarily, is also a safe and sound way for plaiting-.

General information:

It would be interesting to know, how the screws where inserted (by hand or with the drill) and if there would be a lesser chance with nerve injurie by hand use.

I don’t have access to the statistical data.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

2 Nov 2021

Journal Requirements:

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

ANS This manuscript has been revised following the PLOS ONE template.

2. In the Methods section of the manuscript please ensure that you have specified the full name of the university which provided the Cadavers for the study.

ANS The full name of the university has been added in the manuscript on lines 126-127.

3. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

ANS The data has been uploaded in the supporting information files.

4. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript.

ANS This ethic of this study has been approved from the Faculty of Medicine of Prince of Songkla University.

5. Please include a copy of Table 1 which you refer to in your text on page 10.

ANS Table 1 has been added in the manuscript.

Editorial comment:

Please explain in detail why you prefer an anterolateral approach in fracture types carrying a risk of iatrogenic risk of radial nerve as well as profunda brachii artery insteasd of a dorsal approach, which provides a direct visualisation of nerve and vessels.

ANS The anterolateral plating is suitable for a fracture in the area from the proximal to the mid-shaft of the humerus, while the posterior plating is more appropriate for fixations between the mid-shaft and distal humerus. In mid-shaft humeral fixation, the surgeon can use either the anterolateral or posterior plating. In a national survey, both anterolateral and posterior approaches were popular in treating a humeral shaft fracture. There were good to excellent outcomes in both approaches. The complication rates of iatrogenic radial nerve palsy in most studies were similar between the two locations of the plate with incidences of 3.57 – 14.2% in the anterolateral plating and 16.67 – 18.18% using the posterior plating. In contrast, there was one study which reported that the incidence of iatrogenic radial nerve palsy in the anterolateral approach was higher than in the posterior approach. In that study, 46 of 707 humeral shaft fixations had iatrogenic radial nerve injury, compared to 37 cases from the anterolateral approach and 2 cases from the posterior approach. When applying the plate at the anterolateral surface of the bone, there was a risk of iatrogenic radial nerve injury in the steps of drilling a screw hole and/or inserting a screw. In the posterior plating, there was a risk in the step of identifying the radial nerve and profunda brachii artery as they pass across the mid-posterior aspect of the humerus.

A humerus fracture can be caused by a high-energy mechanism and in such cases, the patient will often have associated injuries precluding surgery in the prone or lateral decubitus position. In this study, we used the anterolateral approach because this approach can be done in the supine position, which is suitable for most patients. The posterior approach can be used in either the prone or lateral decubitus positions, although there are contraindications in cases of spinal instability or patients at risk of spinal instability (eg, rheumatoid arthritis), unstable fractures (especially facial and pelvic), anterior burns, chest tubes, and open wounds, shock, pregnancy, recent tracheal surgery, and high intracranial pressure.

Comments to the Author

Review Comments to the Author

Reviewer #1: Basically the authors have found out, that the "2nd proximal screw" is dangerous (100% hits) with other proximal screws (1/3 and 4) being risky (11-67%). The most proximal and all screws distal to the humerus' middle are not risky. Unfortunately, I was not able to open/view Table 1. The figures are all good, instructive and of good quality.

ANS I am sorry you had trouble with this Table. I have carefully checked and re-attached Table 1 in the re-submission.

L82: Dorsal plating with direct visualization of the radial nerve is also a popular technique which needs to be mentioned. I am not so sure that most surgeons prefer anterior plating… (at least not for midshaft fractures and those located more distally)

ANS The posterior approach has been mentioned following your suggestion and the sentence of surgeon preferences has been revised on lines 66-69 and 96-100. The surgeon can use either the anterolateral or posterior plating in a mid-shaft humeral fracture. In a national survey of Ahad et al, both anterolateral and posterior plating were popular in treating a humeral shaft fracture. There were good to excellent outcomes in both approaches. To find the radial nerve in the posterior approach, there were many studies reported the exact soft tissue and bony landmarks to identify the nerve. In contrast, to our knowledge only one study has evaluated the risk of injury in mid-anterior humeral plating, but the results of this study could not be used in anterolateral humeral plating because the direction of the screws is different. It would be beneficial for the surgeon to be able to avoid potential injury to the nerve by knowing the “dangerous” screw holes.

• Ahad A, Haque A, Armstrong A, Modi A, Pandey R, Singh HP. The management of displaced humeral shaft fractures – A survey of UK shoulder and elbow surgeons. Shoulder Elb. 2021;0(0):1-6. doi:10.1177/1758573220986940

L88-91: Why is the plate position different for DCP and LCP, respectively? Aren't they placed the same way?

ANS The plate position is different between the 4.5 mm narrow DCP and the LCP. To provide stability for the DCP, the surgeon should apply the plate at a flat surface which is the anterolateral aspect of the humerus, while it is not necessary to apply the LCP at a flat surface. The LCP can be applied at either the mid-anterior surface or the anterolateral surface of the humerus, as described on lines 84-87. To date, there have been no studies evaluating the risk of radial nerve injury when applying the plate at the anterolateral aspect of the humerus, which is the most common plate location in open humeral shaft fixation.

L100: The authors state that the narrow 4.5 DCP is the most commonly used plate for the humerus shaft. However, no references are provided.... I strongly disagree with the authors. I do not think that is true for Europe and North America and other developed countries.

ANS Thank you for your comment. The phrase of “most commonly used” has been changed to “one of the standard plates” on line 105. As below references, the 4.5 mm narrow DCP is one of the standard plates used in humeral shaft fixation and biomechanical testing between the DCP and LCP has found no statistically significant differences in outcomes in comminuted fractures with good bone quality.

• Gallusser N, Barimani B, Vauclair F. Humeral shaft fractures. EFORT Open Rev. 2021;6(1):24–34.

• O’Toole R V., Andersen RC, Vesnovsky O, Alexander M, Topoleski LDT, Nascone JW, et al. Are locking screws advantageous with plate fixation of humeral shaft fractures? a biomechanical analysis of synthetic and cadaveric bone. J Orthop Trauma. 2008;22(10):709–15.

L 232 Different directions of the drill bit? In LCP the locking screws are inserted in a perpendicular manner as well. I don't see a difference here? Please explain.

ANS The location where the plate is applied is the difference. The 4.5 mm narrow DCP is applied at the anterolateral surface of the humerus while the 4.5 mm narrow LCP applied at either the mid-anterior or anterolateral aspect of the humerus on lines 84-87. There has been, to our knowledge, only one study which evaluated plates applied at the mid-anterior aspect of the humerus, and no studies which have evaluated plates applied at the most common location (anterolateral aspect of the humerus). The screw direction of the 4.5 mm narrow DCP applied at the anterolateral aspect of the humerus projects to the posterolateral area while the screw direction of the 4.5 mm narrow LCP applied at the mid-anterior aspect of the humerus projects to the mid-posterior area.

I would like to have studies discussed which have investigated the anatomical variations of the radial nerve in relation to the humeral bone. This aspect is totally neglected in the discussion. Furthermore, results and complications (regarding the radial nerve and accompanying artery) of anterior humeral plating should be reviewed and discussed with the findings of your study. Only one similar study is (Apivatthakakul et al) is mentioned.

ANS Some discussion of anatomical variations of the radial nerve has been added in the Discussion on lines 260-274. We discussed the results of this study by comparing it with the study of Apivatthakakul et al. because this study seems to be the only study which evaluated the risk of injury based on the hole positions in mid-anterior humeral plating.

I would suggest a more thorough and critical review of the literature regarding the variation of the radial nerve and the accompanying vessels, other experimental studies and results and complications of clinical studies with anterior plating.

ANS Thank you for your suggestion. As noted above, we have added some discussion on this point on lines 271-274.

Reviewer #2:

Line 50: "A hypothetical fracture line was marked at the midpoint of each humerus." Can you provider some data why you choose the fracture line there?

ANS In humeral shaft fractures, the most common fracture location is the middle third of the shaft of the humerus (60%) (as mentioned in the paper referenced below) on lines 49-50, so we located our hypothetical fracture here. For fractures in different areas, the surgeon can use the relative distance ratios we calculated to determine the risk of iatrogenic radial nerve injury.

• Ahad A, Haque A, Armstrong A, Modi A, Pandey R, Singh HP. The management of displaced humeral shaft fractures – A survey of UK shoulder and elbow surgeons. Shoulder Elb. 2021;0(0):1-6. doi:10.1177/1758573220986940

Line 79 Introduction: This part is too short. You should give some feedback information about the percentage of humerus fractures and numbers about prim. and sec. nerve damage.

ANS We have added the requested information on lines 49-58 and 72-79.

Line 80: Can you make some comments about the posterior approach for plating and the percentage of nerve damage from each approach?

ANS Most previous studies reported that the percentage of iatrogenic radial nerve palsy was not statistically different between anterolateral and posterior humeral shaft plating. There has been only one study which found iatrogenic radial nerve injury using the anterolateral plating was higher than in the posterior approach, as mentioned earlier, which reported injuries in 37 of 39 cases from anterolateral plating and 2 of 39 cases from posterior plating on lines 77-79.

Line 92: re-phrase please

ANS This sentence has been revised following your suggestion on lines 50-57.

105-111: please rephrase this very long sentence.

ANS This sentence has been revised following your comment on lines 115-123.

Line 124: can you be more specific what "experienced means with a number of years in experience

ANS The orthopaedist had more than 10 years experience in micro-neurovascular surgery, which has been added in the manuscript on line 173.

Line 215: rephrase in a more scientific way.

ANS This sentence has been revised following the suggestion on lines 243-245.

Line 223: Important discussion/limitations as well is the fact, that the holes this close to the fracture, according the AO-Guidelines, are normally left empty. Please add this as a discussion point.

ANS Thank you for your suggestion. However, we have checked the most recent AO guideline ( https://surgeryreference.aofoundation.org/orthopedic-trauma/adult-trauma/humeral-shaft/simple-fracture-transverse-less-than30/orif-compression-plating#plate-fixation ), which suggests inserting a screw in a pre-drilled hole in fragment close to the fracture and inserting an eccentrical screw into the other fragment near the fracture.

Line 245: I don’t fully see the connection between this two studies. And according to the AO cerclage wiring are not recommended at the humerus shaft.

ANS This paragraph has been removed from the Discussion.

Line 256: What about using a different approach like the posterior one? There are studies out that this approach when used primarily, is also a safe and sound way for plating

ANS There have been several studies which have evaluated the risk of iatrogenic radial nerve injury between the anterolateral and posterior approaches. The incidences were not statistically significantly different between these approaches.

The radial nerve must be identified when using the posterior approach. In a national survey, some surgeons preferred to use the anterolateral approach in humeral shaft plating which does not require pre-identification of the radial nerve and this approach can be done in all patient situations, while the posterior approach can be done in patients in the prone or lateral decubitus positions.

General information:

It would be interesting to know, how the screws where inserted (by hand or with the drill) and if there would be a lesser chance with nerve injurie by hand use.

ANS In this study, we inserted all screws by hand, as described on line 155. We were unable to find any studies comparing safety between hand-inserted and drill-inserted screws. However, if the surgeon is inserting a screw in any danger area, inserting by hand is generally accepted as safer.

Submitted filename: Response to reviewers 30 Oct.docx

Click here for additional data file.

10 Nov 2021

The Risk of Iatrogenic Radial Nerve and/or Profunda Brachii Artery Injury in Anterolateral Humeral Plating using a 4.5 mm Narrow DCP: A Cadaveric Study

PONE-D-21-25577R1

Dear Dr. SUWANNAPHISIT,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Hans-Peter Simmen, M.D., Professor of Surgery

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

18 Nov 2021

PONE-D-21-25577R1

The Risk of Iatrogenic Radial Nerve and/or Profunda Brachii Artery Injury in Anterolateral Humeral Plating Using a 4.5 mm Narrow DCP: A Cadaveric Study

Dear Dr. Suwannaphisit:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Hans-Peter Simmen

Academic Editor

PLOS ONE