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World J Orthop. Feb 18, 2024; 15(2): 110-117
Published online Feb 18, 2024. doi: 10.5312/wjo.v15.i2.110
Review and update on the management of triangular fibrocartilage complex injuries in professional athletes
Valerio Pace, Department of Trauma and Orthopaedics, AOSP Terni, Terni 05100, Italy
Francesco Bronzini, Giovanni Novello, Department of Trauma and Orthopaedics, University of Perugia, Perugia 06100, Italy
Giuseppe Mosillo, Luca Braghiroli, Department of Trauma and Orthopaedics, Hand Unit, AOSP Terni, Terni 05100, Italy
ORCID number: Valerio Pace (0000-0002-4499-9157).
Author contributions: Pace V designed the article; Pace V, Bronzini F, Novello G, Mosillo G and Braghiroli L performed research and literature review, analyzed data, wrote and finalized the review.
Conflict-of-interest statement: No conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Valerio Pace, MBBS, MSc, Researcher, Senior Research Fellow, Surgeon, Department of Trauma and Orthopaedics, AOSP Terni, London HA7 4LP, Terni 05100, Italy. valeriopace@doctors.org.uk
Received: October 20, 2023
Peer-review started: October 20, 2023
First decision: October 24, 2023
Revised: October 30, 2023
Accepted: December 14, 2023
Article in press: December 14, 2023
Published online: February 18, 2024
Processing time: 109 Days and 6.3 Hours

Abstract

Triangular fibrocartilage complex injuries are common in amateur and professional sports. These injuries are mainly caused by acute or chronic repetitive axial loads on the wrist, particularly on the ulnar side and in association with rotations or radial/ulnar deviations. In order to treat professional athletes, a detailed specific knowledge of the pathology is needed. Moreover, the clinician should fully understand the specific and unique environment and needs of the athletes, their priorities and goals, the type of sport, the time of the season, and the position played. An early diagnosis and appropriate management with the quickest possible recovery time are the uppermost goals for both the athlete and the surgeon. A compromise between conservative vs surgical indications, athletes’ needs and expectations, and financial implications should be achieved. Arthroscopic procedures should be timely planned when indicated as they could allow early diagnosis and treatment at the same time. Conservative measures are often used as first line treatment when possible. Peripheral lesions are treated by arthroscopic repair, whilst central lesions are treated by arthroscopic debridement. Further procedures (such as the Wafer procedure, ulnar osteotomies, etc.) have specific indications and great implications with regard to rehabilitation.

Key Words: Triangular fibrocartilage complex injuries; Professional athletes; Ulnar sided wrist pain; Wrist arthroscopy; Wrist debridement

Core Tip: Triangular fibrocartilage complex injuries are common in amateur and professional sports. These injuries are mainly caused by acute or chronic repetitive axial loads on the wrist, particularly on the ulnar side and in association with rotations or radial/ulnar deviations. In order to treat professional athletes, a detailed specific knowledge of the pathology is needed. Moreover, the clinician should fully understand the specific and unique environment and needs of the athletes, their priorities and goals, the type of sport, the time of the season, and the position played. Conservative and surgical management are based on the latter aspects.



INTRODUCTION

The triangular fibrocartilage is a small load-bearing disc-shaped anatomical structure located at the level of the distal part of the ulna and distal radio-ulnar joint, in close relation to the ulnar styloid and the ulnar margin of the distal radius. It is called the “triangular fibrocartilage complex” (TFCC) together with the dorsal and volar distal radio-ulnar ligaments, meniscal homolog, ulno-carpal ligaments and extensor carpi ulnaris tendon sheath. Vascularization is provided by dorsal and palmar branches of the ulnar artery, and palmar branches of the anterior interosseous artery[1-3]. The central portion has reduced regenerative capacities, whilst the peripheral portion is more prone to reparative processes, being provided with a better blood supply compared to the central portion.

The function of the TFCC is to act as a stabilizer for the ulnar aspect of the wrist. It can resist both loading and tensive forces. The TFCC is at risk for either acute traumatic or chronic degenerative injury[1-3]. One can intuitively understand that athletes are at greater risk of acute traumatic injuries to the TFCC rather than degenerative problems.

The diagnostic and therapeutic process can vary between the general population and professional athletes. Several factors must be taken into account in order to choose the most appropriate course of action[1,2].

LITERATURE SEARCH

A narrative review of published papers on the diagnosis and management of TFCC injuries in professional athletes was performed. PubMed, MEDLINE, Cochrane and EMBASE databases were searched. The search keywords were: TFCC injury; triangular fibrocartilage complex injury; TFCC athletes; triangular fibrocartilage complex athletes; TFCC sport; triangular fibrocartilage complex sport; TFCC professional athletes; triangular fibrocartilage complex professional athletes; TFCC treatments; triangular fibrocartilage complex treatments.

All Authors independently performed the review and all included articles were scrutinized. The included articles and results were merged after common agreement among the Authors. Only articles specifically based on the diagnosis and management of TFCC injuries in professional athletes published in the last 20 years were included. In addition, only articles with level of evidence I-II-III-IV were included. Informed consents and ethical approval were not necessary (narrative review).

EPIDEMIOLOGY

Whilst epidemiologic data in the general population have been reported, there is still uncertainty and a lack of high level scientific evidence with regard to the epidemiology of TFCC lesions related to sports. It is reported that these lesions represent between 3% and 9% of the hand-wrist injuries in athletes. It is also reported that the prevalence increases with age[1,2,4,5].

TFCC injuries are common in both amateur and professional sports. These injuries are mainly caused by acute or chronic repetitive axial loads on the wrist, particularly on the ulnar side and in association with rotations or radial/ulnar deviations[1,2,4-9].

Sports that more commonly result in such injuries have been reported to be: Tennis, padel, table tennis, golf, and baseball. Sports that less commonly result in these injuries (but still with a significant number of reported cases) are: Volleyball, basketball, water board sports, and gymnastics[1,2,6-9].

CLASSIFICATIONS

Classifications of TFCC injuries are based on anatomy (central vs peripheral) or more commonly on the etiology. In fact the classification most frequently used is Palmer’s classification, which divides TFCC lesions into 2 groups: Type 1 (acute traumatic injuries) and type 2 (degenerative lesions)[10-12].

Type 1 lesions are further divided into subgroups on the basis of the anatomical location of the lesion: Type 1A (isolated central TFCC articular disc perforation); type 1B (peripheral ulnar sided TFCC tear (with or without ulnar styloid fracture); type 1C (distal TFCC disruption (from the distal ulno-carpal ligament); type 1D (radial TFCC disruption with or without sigmoid notch fracture)[10-12].

Type 2 lesions are also further divided into subgroups: Type 2A (TFCC wear); type 2B (TFCC wear with lunate and/or ulnar chondromalacia); type 2C (TFCC perforation with lunate and/or ulnar chondromalacia); type 2D (TFCC perforation with lunate and/or ulnar chondromalacia and with lunotriquetral ligament perforation); type 2E (TFCC perforation with lunate and/or ulnar chondromalacia, lunotriquetral ligament perforation and ulno-carpal arthritis)[10-12] (Table 1).

Table 1 Palmer’s classification.
Type 1 acute traumatic injury
Type 2 degenerative injury
Isolated central TFCC articular disk perforationTFCC wear
Peripheral ulnar-sided TFCC tear with or without ulnar styloid fractureTFCC wear with lunate and/or ulnar chondromalacia
Distal TFCC disruption (disruption of the distal ulno-carpal ligaments)TFCC perforation with lunate and/or ulnar chondromalacia
Radial TFCC disruption with or without sigmoid notch fractureTFCC perforation with lunate and/or ulnar chondromalacia and with lunotriquetral ligament perforation
TFCC perforation with lunate and/or ulnar chondromalacia, lunotriquetral ligament perforation and ulno-carpal arthritis
DIAGNOSIS

The most common symptoms of a TFCC injury are: Ulnar-sided wrist pain with tenderness mainly found at the level of the fovea; ulnar-sided minimal oedema; pain against resistance; reduced range of motion (ROM) of the wrist; joint sagging during rotations or load-bearing activities; audible and palpable “click” from the ulnar side of the wrist during forearm rotations (prono-supination) and sometimes radial and/or ulnar deviation. Pain and reduced function on radio-ulnar deviation can be characteristic of an ulnar impaction syndrome. Injuries can be asymptomatic or pauci-symptomatic[13-17].

Athletes often report sudden occurrence of pain during forearm rotations and axial-loading of the wrist. Different combinations of axial-loading, rotation and radial or ulnar deviations have been reported. Direct trauma on the ulnar side of the wrist is a rare but existing occurrence, especially with the wrist in radial deviation. Another possible finding is a chronic lesion caused by repetitive movements of the wrist and mechanical stress in general of the distal radio-ulnar joint[13,14,18].

These symptoms related to a TFCC injury are often reported by athletes playing sports involving significant axial-load and mechanical stress on the wrist, particularly if the axial-load is associated with rotations and radial/ulnar deviations (such as tennis, padel, golf, ping-pong, baseball, javelin etc.)[13-18].

An association between TFCC injuries and other major musculoskeletal lesions (such as Colles’ fractures, Galeazzi’s injury, Essex-Lopresti injury, etc.) in athletes competing in sports involving strong body contact such as football, rugby, etc. has rarely been reported [1,2,4,5].

If the TFCC injury is significant, the athlete is rarely able to continue to the end of the training sessions or games/competitions given the significant pain and wrist motion impairment.

Specific tests introduced in order to evaluate wrist stability are as follows: Ulnar fovea sign, piano key test, ulnar grinding test, compression test, and the ballottement test[1,2,19,20] (Table 2).

Table 2 Diagnosis of TFCC injuries.
Clinical tests
Radiological tests
Areas of tendernessX-ray (AP and lateral view)
Ulnar fovea signCT (rarely)
Piano key testMRI
Ulnar grinding testWrist arthrogram
Compression testWrist arthroscopy (gold standard)
Ballottement test
ROM evaluation

The next step is radiology. A plain radiograph is a must (at least the common antero-posterior (AP) and lateral view) and is the simplest and quickest radiological exam performed. It is of absolute relevance to identify any fractures (especially affecting the ulnar styloid), measure the standard radiological parameters of the wrist (ulnar variance in particular on the AP view), exclude a subluxation of the distal radio-ulnar joint (by examining the lateral view) and evaluate the potential presence of an ulnar impaction syndrome (especially in degenerative lesions)[1,2,16,19,20] (Table 2).

A computed tomography scan is rarely recommended, and is indicated only in cases of intra-articular fractures of the wrist. A wrist magnetic resonance imaging (MRI) scan is often indicated for TFCC injuries. Its sensitivity and specificity vary depending on the level of resolution of the scanning machine. High resolution MRI scans provide a level of accuracy up to 97%[1,2,16,19,20] (Table 2).

A wrist arthrogram is an option very commonly used in some units as this exam allows visualization of the lesion location and defines the characteristics of the TFCC lesion[1,2,16] (Table 2).

However, the literature indicates that wrist arthroscopy is the gold standard for TFCC injury diagnosis and to potentially allow appropriate treatment simultaneously. It is considered the test with the highest sensitivity and specificity, provides the opportunity to directly visualize the anatomical structures and make a specific diagnosis, and allows arthroscopic treatment at the same time (debridement or repair). Several arthroscopy portals and repair techniques have been reported in the literature, which are chosen specifically depending on the type of patient and lesion[1,2,21,22]. Specific aspects related to the choice and timing of radiological examinations will be discussed in the following sections.

TREATMENTS
Conservative treatments

Athletes with a TFCC injury, after the appropriate diagnostic process, are very often prone to attempt conservative measures first, before more invasive options. However, this will be further developed in this article as many specific factors must be considered when making such decisions[1,2,20,21].

The following conservative measures are applied in different combinations: No sport activity for 3-6 wk (depending on the severity of the injury); immobilization with a splint for 2-4 wk; utilization of non-steroidal anti-inflammatory agents (oral and/or topical); one or more steroid injections and/or hyaluronic acid injections; physical therapy; occupational therapy[1,2,21-24].

If it is necessary for the athlete to carry on to the end of the competitive season or a specific game/competition (weeks or months), the clinician should postpone the surgical treatment until the annual break and carry out the above-mentioned conservative strategies, if the severity of the injury allows and bearing in mind that the athlete must perform at a certain high level. However, if the TFCC injury is very severe and strong surgical indications are defined, especially in the absence of imminent relevant competitions, the orthopaedic surgeon could recommend surgical repair straight away, with the aim of achieving the quickest possible recovery and return to sport activity avoiding long-term degenerative complications[1,2,22-24].

It is suggested that an experienced multidisciplinary team centered on an orthopaedic surgeon with strong experience in hand and wrist surgery should be involved in the treatment of elite athletes with TFCC injuries. In fact, injury management errors would be particularly evident when dealing with professional athletes and significant consequences could be caused by little mistakes. We stress again the importance of the initial decision on the timing of surgical repair: The athlete’s entire career is at stake and this “crossroad” is the key management decision that could positively or negatively affect the outcome of treatment[1,2].

Surgical treatments

Type 1A lesions: Isolated central TFCC articular disk perforation. These lesions are avascularized and cannot be arthroscopically repaired. Therefore arthroscopic debridement is the surgical treatment of choice. It is reported in biomechanics studies that up to 80% of the disc could be debrided/removed without causing any significant wrist instability. A standard arthroscopic set up is usually required with the use of 2 portals (rarely 3 portals)[1,2,18-24].

Surgery is followed by 1 or 2 wk of wrist immobilization. This is followed by a rehabilitation program based on passive and active wrist movements. Athletes playing sports requiring strong wrist stress forces (tennis, golf, javelin, padel, etc.) are allowed light ball contact after 3 wk. Full return to sport is expected between 4 to 6 wk[1,2,18-24].

If a type 1A lesion is associated with neutral or positive ulnar variance, it may be necessary to perform a shortening ulnar osteotomy or a Wafer-procedure after debridement. The osteotomy could be postponed to the end of the season with the aim of allowing the injured athlete to return to high level performance in a few weeks and manage the remaining problem at the end of the season. The rehabilitation program after an osteotomy could last up to 3-4 mo (it requires immobilization for 6-8 wk) and the entire season could be at risk[1,2,18-24].

Type 1B lesions: Peripheral ulnar-sided TFCC tear with or without ulnar styloid fracture. These lesions are vascularized and can potentially be repaired. Using an inside-out, outside-in or all-inside technique, the lesion is arthroscopically repaired[1,2].

The rehabilitation program includes immobilization (splint or cast) for 4-6 wk, and then a further 6 wk of passive and active wrist exercises to regain an adequate ROM and muscle strength. The program may take up to 3 mo[2,18-24].

Type 1C lesions: Distal TFCC disruption (disruption of the distal ulno-carpal ligaments). These lesions are often diagnosed without arthroscopy and mainly require an open surgery repair. An incision on the ulnar side of the wrist just volar to the extensor carpi ulnaris should be made and the neurovascular structures carefully protected throughout the entire procedure. Following appropriate exposure, the lesion can be directly repaired; several techniques have been described[1,2,18-24].

Type 1D lesions: Radial TFCC disruption with or without sigmoid notch fracture. An arthroscopic repair is suggested for these lesions, together with thorough debridement of the sigmoid notch, particularly at the level of the triangular fibrocartilage insertion[1,2,18-24].

Type 2A lesions: TFCC wear. Symptoms related to these lesions may be insidious. Radiographs are necessary in order to rule out and diagnose degenerative changes in the distal radio-ulnar joint and evaluate the ulnar variance. Elite athletes are often offered surgical management including a shortening ulnar osteotomy for those with neutral or positive ulnar variance. However, the latter is contraindicated in the presence of radio-ulnar joint arthritis. In this case a distal ulnar resection is proposed[1,2,18-24].

Type 2B lesions: TFCC wear with lunate and/or ulnar chondromalacia. The treatment options do not differ from those related to type 2A lesions[1,2,18-24].

Type 2C lesions: TFCC perforation with lunate and/or ulnar chondromalacia. These lesions are treated by arthroscopic debridement and a Wafer resection procedure for those with neutral or positive ulnar variance. If the latter is bigger than 2 mm, a shortening ulnar osteotomy is recommended instead[1,2,18-24].

Type 2D lesions: TFCC perforation with lunate and/or ulnar chondromalacia and with lunotriquetral ligament perforation. This type of lesion rarely affects elite athletes as significant degenerative processes do not generally occur before 30-40 years of age. The treatment does not differ from that of 2C lesions, apart from the necessity to evaluate the stability of the lunotriquetrel ligament. Consequently a Wafer procedure is contraindicated in the case of instability, and accurate debridement of the ligament is also necessary. If instability persists even after the osteotomy procedure, a lunotriquetral arthrodesis should be considered as a second stage treatment option in those whose symptoms do not improve after osteotomy[1,2,18-24].

Type 2E lesions: TFCC perforation with lunate and/or ulnar chondromalacia, lunotriquetral ligament perforation and ulno-carpal arthritis. In the presence of degenerative changes, Wafer procedures and osteotomies are not indicated in these patients. The well studied salvage procedure called Sauve-Kapandji (or hemiresection arthroplasty) is a suitable option for these cases. A Sauve-Kapandji procedure is the treatment of choice for elite athletes as it offers the lowest risk of radio-ulnar impingement during sport activities[1,2,18-24]. The rehabilitation protocol of type 2 lesions does not differ from those described above.

Sport-specific treatments

The treatment of choice may depend and vary on several factors. The clinician should take into account the level of pain and movement limitations, the type of lesion, the severity of the injury, the level of competition, the timing of the injury in relation to the stage of the agonistic season, sport, and position played by the athlete[1,2,22-27].

Very early diagnosis is the key step for elite athletes as this allows early identification of the problem and subsequent early treatment planning. If temporary immobilization is advocated, professional athletes are often very reluctant to be compliant with this treatment strategy. Moreover, athletes participating in sports involving repetitive pronation/supination and radial/ulnar deviation do not significantly benefit from this type of conservative measure and very often immobilization is avoided[5,16,17].

On the other hand, steroid injections (with or without the use of hyaluronic acid) seem to be a quite common temporary or definitive option for professional athletes. These injections are indicated for injuries that do not have surgical indications or for injuries with surgical indications in athletes who are willing to end the season before undergoing surgery. However, there are exceptions: In the presence of radio-ulnar instability, central lesions (an early arthroscopic procedure for central lesions allows both an early and accurate diagnosis and appropriate surgical management at the same time, assuring the shortest rehabilitation time), and lesions associated with neutral or positive ulnar variance (debridement is initially needed, after which further surgical treatments are considered and evaluated in the following months), a prompt surgical plan is warranted[1,2,18-24].

Different to the surgical timing for central lesions, peripheral lesions with surgical indication do not need immediate surgical planning. Careful discussion (with pros and cons evaluation) between the athlete and the surgeon should take place with a shared final decision on whether to decide on a conservative or surgical option. As mentioned previously, several factors should be taken into account and the decision should be athlete-centred and specific. If the type of injury allows, many opt for temporary measures (steroid injections prevalently) in order to complete at least the season. In fact a surgical option implies the need for at least 3 mo rehabilitation. More invasive treatments such as Wafer procedures are very commonly delayed until the end of the season, whilst ulnar osteotomies are widely postponed at least until the end of the season, if not to the end of the professional career[1,2,18-24].

The major issue for all athletes whose injuries have a surgical indication but are treated temporarily with conservative measures until the end of the season, is the possibility of compromising the final surgical results and increasing the risk of medium- and long-term consequences (such as degenerative changes)[1,2,18-24].

SPORT-SPECIFIC REHABILITATION INSIGHT

It is known that central lesions can be treated arthroscopically. Patients are required to use a splint for 1 to 2 wk after the surgical procedure and then start passive and active ROM exercises. Athletes playing sports such as golf are usually able to start their routine training (including ball-contact) after about 3 wk. Full return to competitive sport activities can be achieved in 4-6 wk in these patients. On the contrary, for sports involving significant axial loading forces onto the wrist (such as boxing and gymnastics) full return to competition level may take up to 8-12 wk. Athletes playing sports involving frequent and intense radial-ulnar deviation and rotations of the wrist (such as tennis and padel) may return to competitions in approximately 6-8 wk[1,2,22-27].

The rehabilitation protocol after arthroscopic debridement for peripheral lesions is longer than that described above. In fact, patients require a period of immobilization with a splint or cast for 2-6 wk. This should be followed by a further 6-8 wk of passive and active wrist ROM exercises and strengthening exercises. The return to competitive sport activity may be achieved after 2-3 mo, independent of the type of sport[1,2,22-27].

The return to sport might take longer following surgical treatment of type 2 lesions. A Wafer procedure requires 1-2 wk of immobilization in a splint or cast which should be followed by early active exercises first and strengthening exercises in the second stage. Full return to competition is authorized after 6-8 wk minimum depending on symptoms: The athlete can compete at the end of the rehabilitation protocol when pain free. No differences among the types of sport have been reported[1,2,18-27].

A shortening osteotomy requires 5-6 wk of immobilization, preferably with a cast. This is followed initially by passive and active ROM exercises of the wrist and then by strengthening exercises. Full return to competitive sport may be achieved after 10-12 wk at the earliest. Full bone healing (with radiological evidence from plain radiographs) is necessary in order to allow the athlete to compete again[1,2,18-27].

Elite athletes playing certain sports can be aided by the use of taping, splinting or padded casts, especially after Wafer or osteotomy procedures in order to reduce stress. However, not all sports allow the use of these aids. In fact, athletes playing ball contact sports (such as rugby, football, baseball and tennis) cannot fully compete if they require these aids and their rehabilitation protocol might take longer than expected as a consequence. Therefore, protective equipment varies between non-contact and contact sports, and its use may vary even among different roles played by the athletes within the same sport activity[1,2,18-27].

In general, a professional athlete with key roles within the team or with very high potential and expectations can wait until the end of the season to undergo a surgical procedure after sustaining a TFCC injury (and utilize temporary measures such as steroid injections); moreover, the rehabilitation protocols tend to be more intense as the quickest possible return to sport is attempted. On the other hand, professional athletes with lower expectations decide on surgical treatment at an earlier stage and a slightly more prudent rehabilitation protocol is adopted[1,2,18-27].

With regard to throwing sports, if the lesion affects the non-throwing arm, the return to competitive sport may be achieved quicker at 2 to 4 wk compared to standard rehabilitation protocols for all types of TFCC injuries and surgical treatments[1,2,18-27].

Patient education is absolutely essential in order to allow the best possible rehabilitation, avoid further injuries and disease progression in those conservatively treated (or whilst waiting until the end of the season for definitive surgical management). Activities reproducing the mechanism of injury and pain should be avoided[1,2,18-29].

CONCLUSION

TFCC injuries are common in amateur and professional sports. These are mainly caused by acute or chronic repetitive loads on the wrist, particularly on the ulnar side. This is even worse if axial loads are associated with rotations or radial/ulnar deviations.

In order to treat professional athletes who sustain TFCC injuries, a detailed specific knowledge of the pathology is needed. Moreover, the clinician should fully understand the specific and unique environment and the needs of the athletes, their priorities and goals, the type of sport, the time of the season, and the position played.

An early diagnosis and appropriate management with the quickest possible recovery time are the uppermost goals for both the athlete and the surgeon. A compromise between conservative vs surgical indications, athletes’ needs and expectations, and financial implications should be achieved. Arthroscopic procedures should be timely planned when indicated as they may allow early diagnosis and treatment at the same time.

Conservative measures are often used as first line treatment when possible. Peripheral lesions are treated by arthroscopic repair, whilst central lesions are treated by arthroscopic debridement. Further procedures (such as the Wafer procedure, ulnar osteotomies, etc.) have specific indications and great implications with regard to the rehabilitation time and long-term consequences for the athletes.

Competitive levels are very often achieved by athletes with TFCC injuries surgically. Only a small percentage do not reach satisfactory levels, and this is more common in those undergoing repair procedures or procedures related to radial/ulnar instability and neutral or positive ulnar variance.

Footnotes

Provenance and peer review: Unsolicited article; Externally peer reviewed.

Peer-review model: Single blind

Corresponding Author's Membership in Professional Societies: General Medical Council (United Kingdom), No. 7192447.

Specialty type: Orthopedics

Country/Territory of origin: Italy

Peer-review report’s scientific quality classification

Grade A (Excellent): A

Grade B (Very good): B, B

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Farì G, Italy; Widmer KH, Switzerland S-Editor: Fan JR L-Editor: Webster JR P-Editor: Zhao S

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