Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver.

Normothermic machine perfusion (NMP) has emerged as an innovative organ preservation technique. Developing an understanding for the donor organ immune cell composition and its dynamic changes during NMP is essential. We aimed for a comprehensive characterization of immune cell (sub)populations, cell trafficking and cytokine release during liver NMP. Single-cell transcriptome profiling of human donor livers prior to, during NMP and after transplantation shows an abundance of CXC chemokine receptor 1+/2+ (CXCR1+/CXCR2+) neutrophils, which significantly decreased during NMP. This is paralleled by a large efflux of passenger leukocytes with neutrophil predominance in the perfusate. During NMP, neutrophils shift from a pro-inflammatory state towards an aged/chronically activated/exhausted phenotype, while anti-inflammatory/tolerogenic monocytes/macrophages are increased. We herein describe the dynamics of the immune cell repertoire, phenotypic immune cell shifts and a dominance of neutrophils during liver NMP, which potentially contribute to the inflammatory response. Our findings may serve as resource to initiate future immune-interventional studies.

The liver-resident immune cell repertoire - A boon or a bane during machine perfusion?

The liver has been proposed as an important "immune organ" of the body, as it is critically involved in a variety of specific and unique immune tasks. It contains a huge resident immune cell repertoire, which determines the balance between tolerance and inflammation in the hepatic microenvironment. Liver-resident immune cells, populating the sinusoids and the space of Disse, include professional antigen-presenting cells, myeloid cells, as well as innate and adaptive lymphoid cell populations. Machine perfusion (MP) has emerged as an innovative technology to preserve organs ex vivo while testing for organ quality and function prior to transplantation. As for the liver, hypothermic and normothermic MP techniques have successfully been implemented in clinically routine, especially for the use of marginal donor livers. Although there is evidence that ischemia reperfusion injury-associated inflammation is reduced in machine-perfused livers, little is known whether MP impacts the quantity, activation state and function of the hepatic immune-cell repertoire, and how this affects the inflammatory milieu during MP. At this point, it remains even speculative if liver-resident immune cells primarily exert a pro-inflammatory and hence destructive effect on machine-perfused organs, or in part may be essential to induce liver regeneration and counteract liver damage. This review discusses the role of hepatic immune cell subtypes during inflammatory conditions and ischemia reperfusion injury in the context of liver transplantation. We further highlight the possible impact of MP on the modification of the immune cell repertoire and its potential for future applications and immune modulation of the liver.

Static cold storage compared with normothermic machine perfusion of the liver and effect on ischaemic-type biliary lesions after transplantation: a propensity score-matched study.

BACKGROUND: Given the susceptibility of organs to ischaemic injury, alternative preservation methods to static cold storage (SCS), such as normothermic machine perfusion (NMP) are emerging. The aim of this study was to perform a comparison between NMP and SCS in liver transplantation with particular attention to bile duct lesions. METHODS: The outcomes of 59 consecutive NMP-preserved donor livers were compared in a 1 : 1 propensity score-matched fashion to SCS control livers. Postoperative complications, patient survival, graft survival and bile duct lesions were analysed. RESULTS: While patients were matched for cold ischaemia time, the total preservation time was significantly longer in the NMP group (21 h versus 7 h, P < 0.001). Patient and graft survival rates at 1 year were 81 versus 82 per cent (P = 0.347) and 81 versus 79 per cent (P = 0.784) in the NMP and SCS groups, respectively. The postoperative complication rate was comparable (P = 0.086); 37 per cent NMP versus 34 per cent SCS patients had a Clavien-Dindo grade IIIb or above complication. There was no difference in early (30 days or less) (NMP 22 versus SCS 19 per cent, P = 0.647) and late (more than 30 days) (NMP 27 versus SCS 36 per cent, P = 0.321) biliary complications. However, NMP-preserved livers developed significantly fewer ischaemic-type bile duct lesions (NMP 3 versus SCS 14 per cent, P = 0.047). CONCLUSION: The use of NMP allowed for a significantly prolonged organ preservation with a lower rate of observed ischaemic-type bile duct lesions.

Integrating interventional oncology in the treatment of liver tumors.

BACKGROUND: Percutaneous ablation techniques offer a vast armamentarium for local, minimally invasive treatment of liver tumors, nowadays representing an established therapeutic option, which is integrated in treatment algorithms, especially for non-resectable liver tumors. The results of ablative treatment compare very well to surgical treatment in liver lesions, and confirm that these techniques are a valuable option for bridging for transplantation. Different techniques have been established to perform tumor ablation, and the feasibility varies according to the procedure and technical skills of the operator, depending on the size and location of the liver lesion. In recent years, stereotactic multi-needle techniques using 3D trajectory planning, general anesthesia, and tube disconnection during needle placement have had a strong impact on the application range of ablation for liver tumors. CONCLUSION: It is well known that creating a sufficient ablation margin and overlapping ablation zones is one key issue to enable ablation of large liver lesions with tumor-free margins (A0 ablation in analogy to R0 resection). Image fusion during treatment and follow-up assure highly accurate staging procedures and interventional planning. NOVEL ASPECTS: Review on the standards in ablation techniques for the treatment of liver tumors. Update on different ablation techniques, indications, and contraindications for percutaneous liver tumor treatment. Summary of recently published reports on liver tumor ablation.

[Arthroscopy of the distal radioulnar joint]. / Die Arthroskopie des distalen Radioulnargelenks.

OBJECTIVE: The aim of the procedure is to visualize the proximal pouch of the DRUJ, the joint surfaces of the sigmoid notch and the ulnar head, the convexity of the ulnar head and the proximal ulnar side surface of the triangular fibrocartilage complex (TFCC). INDICATIONS: Arthroscopy of the distal radioulnar joint is applied for the evaluation of joint pathologies in ulnar-sided wrist pain, especially in cases without diagnostic findings in standard X­rays and MRIs and arthroscopically assisted procedures. SURGICAL TECHNIQUE: In vertical extension, two portals of the wrist are created on the dorsal side of the DRUJ between the extensor digiti minimi and extensor carpi ulnaris tendons. By insertion of a small joint arthroscope via these portals visualization of the ulnar head, the sigmoid notch, the proximal pouch of the DRUJ and the proximal surface of the TFCC is accomplished. CONCLUSIONS: Arthroscopy of the DRUJ is a rarely and not routinely performed procedure for the diagnosis and therapy of ulnar-sided wrist pain. It is technical demanding with a flat learning curve and anatomy-related obstacles. A complete view of the joint is not always accessible. Rare complications are injuries of the extensor digiti minimi tendon, as well as contusion or sectioning of the transverse branch of the dorsal branch of the ulnar nerve. In distinct cases, this procedure offers important additional information about the distal radioulnar joint. The procedure is especially valuable for the detection of proximal TFCC injuries that are missed otherwise.

[Grip strength measurement : Significance and boundaries]. / Die Messung der Griffkraft : Wertigkeit und Grenzen.

BACKGROUND: Grip strength measurement is a widely used method for clinical as well as scientific purposes. In hand surgery, it is an essential component in the diagnosis of disease, treatment sequences and assessment. In epidemiological studies, it is a good predictor of healthy ageing or disease progression. PROBLEM: Measurement results and their interpretation can be influenced by many factors. The historical development of dynamometry, measurement technology and the standard values in various population groups are presented. Comparisons with standard values should only be made using current tables because the grip strength has changed in recent decades. Assessment of the voluntarily submaximal grip strength remains problematic. Proposals are made for how to assess grip strength during the evaluation.

[Arthrodesis of the trapeziometacarpal joint]. / Die Arthrodese des Daumensattelgelenks.

OBJECTIVE: Bony fusion of the trapeziometacarpal joint. INDICATIONS: High demands concerning stability and strength of the thumb in primary or secondary osteoarthritis (e.g., posttraumatic osteoarthritis following injuries to the carpometacarpal joint of the thumb); instability in the absence of osteoarthritis due to malformations, ligamentous laxicity, and joint hypermobility; malformations; improvement of hand function in neurological disorders; salvage procedure after carpometacarpal arthroplasty provided bone stock is sufficient. CONTRAINDICATIONS: Osteoarthritis or stiffness of adjacent joints, activities demanding maximal mobility of the thumb, insufficient bone stock. SURGICAL TECHNIQUE: Resection of the articular surfaces of the trapeziometacarpal joint via a dorsal approach. After temporary K­wire transfixation, application of a dorsal T­shaped plate (fixed angled or not), replacement of the K­wire with a lag screw. POSTOPERATIVE MANAGEMENT: Immobilization for 8 weeks (radial below-elbow cast including the thumb metacarpophalangeal joint); standard radiographs on second postoperative day and after 8 weeks; removal of stitches after 2 weeks; with bony healing after removal of the cast, guided exercises to increase strength and mobility; full loading for manual tasks after 3 months. RESULTS: With regards to strength, stability, and pain reduction, results are rated as good and excellent with a high degree of patient satisfaction. Disadvantages are implant-related complications and nonhealing of the fusion in an average of 13% of patients. Nevertheless, the procedure is still indicated in young manual workers who tolerate some limitations of mobility.

Diagnosing central lesions of the triangular fibrocartilage as traumatic or degenerative: a review of clinical accuracy.

This study examined the reliability of surgeons' estimations as to whether central lesions of the triangular fibrocartilage complex were traumatic or degenerative. A total of 50 consecutive central triangular fibrocartilage complex lesions were independently rated by ten experienced wrist surgeons viewing high-quality arthroscopy videos. The videos were reassessed after intervals of 3 months; at the second assessment surgeons were given the patient's history, radiographs and both, each in a randomized order. Finally, the surgeons assessed the histories and radiographs without the videos. Kappa statistics revealed fair interrater agreement when the histories were added to the videos. The other four modalities demonstrated moderate agreement, with lower Kappa values for the assessment without videos. Intra-rater reliability showed fair agreement for three surgeons, moderate agreement for two surgeons and substantial agreement for five surgeons. It appears that classification of central triangular fibrocartilage complex lesions depends on the information provided upon viewing the triangular fibrocartilage complex at arthroscopy. LEVEL OF EVIDENCE: II.

[Carpus and distal radioulnar joint : Clinical and radiological examination]. / Carpus und distales Radioulnargelenk : Klinische und röntgenologische Untersuchung.

A precise medical history and specific symptom-oriented clinical tests of the wrist joint should always precede any radiological, computed tomography (CT) or magnetic resonance imaging (MRI) diagnostics. In many cases, specific clinical tests of the wrist joint allow at least a preliminary diagnosis, which can be supported by standard radiography using correct projections. A systematic approach is recommended covering the radiocarpal, midcarpal, ulnocarpal and distal radioulnar joints. Exact identification of the palpable anatomic landmarks is mandatory for correct application and interpretation of the various clinical tests. The results of the clinical tests in combination with radiological imaging can often detect precisely ruptures of distinct wrist joint ligaments and localized arthritis.

[Reconstruction of the Distal Radioulnar Ligaments According to Adams: Surgical Technique - A Video]. / Rekonstruktion der distalen radioulnaren Bänder nach Adams: Operationstechnik - ein Video.

This paper describes the surgical technique to reconstruct the distal radioulnar ligaments using the palmaris longus tendon as inaugurated by Brian Adams. A video can be approach online.

[Aptis Prosthesis for the Treatment of Painful Instability of the Ulnar Stump Following Wide Excision of the Distal ulna]. / Aptis-Prothese bei schmerzhafter Instabilität des Ulnastumpfes nach hoher Resektion der Ulna.

We report the case of 35-year-old woman with severe Madelung's deformity. Having undergone a Kapandji-Sauvé-procedure with wide excision of the distal ulna, the patient suffered from painful instability of the ulnar stump. Although a corrective osteotomy of the distal radius had been performed, severe ulnar inclination of the distal radius remained, leaving persisting pain. Implantation of a constrained distal radioulnar joint prosthesis combined with a renewed extraarticular corrective osteotomy of the distal radius was performed. The peg of the radial plate of the prosthesis was placed in the screw hole of the large-fragment lag screw removed after the Kapandji-Sauvé-procedure.

[Hand injuries in mountain sports]. / Handverletzungen beim Bergsport.

BACKGROUND: Apart from clean cut finger amputations, every kind of hand injury can be seen in mountain and winter sports but only skier's thumb and injuries of the pulley system in sport climbers are seen in a greater number of cases. Nevertheless, these two common injuries as well as the rare frostbite of the fingers are often underdiagnosed or overdiagnosed as well as undertreated or overtreated. PURPOSE: This paper describes the diagnostics and treatment of skier's thumb, injuries of the pulley system in sport climbers and frostbite of the fingers. RESULTS: Before checking the metacarpophalangeal (MP) joint of the thumb for stability, radiographs should be taken to exclude a bony avulsion of the ulnar collateral ligament in skier's thumb. If there is no bony ligament avulsion further diagnostic procedures, e.g. ultrasound, are recommended to prove or exclude a Stener lesion, which is an absolute indication for operative treatment together with a dislocated bony ligament avulsion. To quantify the severity of a lesion of the pulley system ultrasound and magnetic resonance imaging (MRI) are needed. Most lesions of the pulley system can be treated conservatively. Only multiple pulley ruptures or isolated ruptures associated with a lesion of the lumbrical muscles or collateral ligaments require operative treatment. As long as there is no infection amputation should be done as late as possible in frostbite of the fingers because the extent of the frostbite can rarely be correctly estimated. CONCLUSION: Most cases of skier's thumb as well as lesions of the pulley system can be treated non-operatively but precise diagnostics are needed.

[Scapholunate lesions]. / Die skapholunäre Bandverletzung.

Injuries to the scapholunate ligament are the most frequent cause of carpal instability. Therefore, if a scapholunate lesion is not diagnosed, it may result in a severe dysfunction of the wrist. This review describes the anatomy, and the kinematics of the wrist with an intact as well as a disrupted scapholunate ligament. The diagnostic of an isolated ligament lesion and a ligament injury associated with a fracture of the distal radius is presented. Finally, an algorithm for treatment based on the stage of injury is proposed.

[Median nerve neuropathy after perilunate dislocation injuries]. / Neuropathie des N. medianus nach perilunären Luxationsverletzungen.

PURPOSE: The purpose of this retrospective study was to investigate the frequency and appearance of median nerve neuropathy following perilunate dislocation injuries with respect to the preceding surgical decompression and the clinical outcome. PATIENTS AND METHODS: 32 patients were followed for a mean of 65 months after surgery for perilunate dislocation, including carpal tunnel release in 13 patients. 10 of 11 patients with clinical symptoms of median nerve affection at follow-up had additionally an electrophysiological examination. Median neuropathy was assumed if 2 or more parameters were pathologic. Patients with and without median neuropathy were compared. The DASH score, pain, wrist motion, grip strength and the Mayo wrist score were used to rate the outcome. RESULTS: In 6 patients, neuropathy of the median nerve persisted since injury in spite of carpal tunnel release in 5 of them. 3 patients showed secondary, delayed median nerve affection. Patients with median neuropathy had a worse result with regard to pain at rest, grip force, the DASH score, and the Mayo wrist score. The difference was statistically significant for pain with activities. CONCLUSION: Median neuropathy following perilunar dislocation injuries is frequent. It appears rather like a chronic neural lesion than a typical compression syndrome. A primary carpal tunnel release cannot always prevent persistent neural disorders.

[Injuries of the proximal interphalangeal joint]. / Verletzungen der Mittelgelenke.

BACKGROUND: Injuries of the proximal interphalangeal joint (PIP joint) are common. They are frequently underestimated by patients and initial treating physicians, leading to unfavorable outcomes. Basic treatment includes meticulous clinical and radiological diagnosis as well as anatomical and biomechanical knowledge of the PIP joint. TREATMENT: In avulsions of the collateral ligaments and the palmar plate with or without involvement of bone, nonoperative treatment is preferred. Operative stabilization is reserved for large displaced bony fragments or complex instabilities. In central slip avulsion or rupture, osseous refixation, suture, or reconstruction is common and nonoperative treatment is limited to special situations like minimally displaced avulsions. In basal fractures of the middle phalanx, elimination of joint subluxation and restoration of joint stability are priority. If the fragments are too small for fixation with standard implants, therapeutic alternatives include refixation of the palmar plate, dynamic distraction fixation, percutaneous stuffing, or replacement by a hemihamate autograft. Early motion is initiated regardless of the treatment regime. Undertreatment leads to persistent swelling, instability, and limited range of motion, which are difficult to treat. Contributing factors are unnecessary immobilization, immobilization in more than 20° flexion or transfixation by K-wires. For residual limitations, nonoperative treatment with physiotherapists and splinting is first choice. Operative treatment is reserved for persistent flexion/extension contractures persisting for more than 6 months, as well as reconstructions in boutonniere and swan neck deformity and salvage procedures for destroyed joints.

[Malunion of the distal radius - long-term results after extraarticular corrective osteotomy]. / Die fehlverheilte distale Radiusfraktur - Langzeit-ergebnisse nach extraartikulärer Korrekturosteotomie.

BACKGROUND AND PURPOSE: Numerous reports on short- and mid-term results demonstrate the value of corrective osteotomies for malunion of the distal radius. However, only long-term results can show whether a procedure has stood the test of time. Therefore the main questions to be answered in this article are: (i) are clinical and radiological improvements, recorded at short- and mid-term follow-up, long lasting? (ii) are consecutive procedures required, especially salvage procedures?; and (iii) what about the development of post-traumatic osteoarthritis? PATIENTS AND METHODS: The study is based on the prospective data of 17 patients who underwent an extraarticular corrective osteotomy of the distal radius for symptomatic malunion (13 dorsal and 4 palmar malunions) between August 1992 and August 2003. The corrective osteotomy was performed as an opening wedge osteotomy filling the gap with an iliac crest bone graft and stabilisation of the radius with a plate. In 16 patients the radius was approached from palmar, in one patient the approach was dorsal. Preoperative, at short-term and at long-term postoperative follow-up clinical and radiological examinations were performed. In dorsal malunion the mean short-term follow-up was 17±10 (range: 7-44) months, and the mean long-term follow-up was 157±51 (120-254) months. In palmar malunion, the short-term follow-up averaged 13±6 (7-20) months, and the long-term follow-up 150±10 (138-166) months. RESULTS: All osteotomies showed bony union. One patient had to be excluded from the long-term evaluation due to wrist fusion and ulnar head hemiresection after 15 years. After dorsal malunion the long-term results showed a lasting improvement for all parameters. A comparison of short-term and long-term results revealed no deterioration of the results but a further statistically significant improvement in grip strength. 7 patients had no osteoarthritis, 3 osteoarthritis 1°, 1 osteoarthritis 2°, and 1 osteoarthritis 3°. After palmar malunion improvements occurred and lasted in the long-term run, but were not statistically significant. In this group no osteoarthritis was present. CONCLUSION: Corrective osteotomy for malunion of the distal radius has stood the test of time even in the long-term course. Even from this point of view, it can be recommended.

[Restoration of thumb flexion at the interphalangeal joint by transposition of the flexor digitorum superficialis tendon from the ring finger]. / Wiederherstellung der Daumenendgelenkbeugung durch Transposition der oberflächlichen Beugesehne des Ringfingers.

OBJECTIVE: Restoration of active thumb flexion at the distal joint. INDICATIONS: Loss of active flexion of the interphalangeal (IP) joint of the thumb if there is a transection of the flexor pollicis longus (FPL) tendon at the tendon channel of the thumb or thenar and direct suture is not possible but the tendon channel is intact, as alternative procedure to a free tendon graft if the transection is proximal to the tendon channel and the muscle of the FPL is contracted/injured or the FPL tendon is unharmed but the FPL muscle is partially or complete paralyzed. CONTRAINDICATIONS: Insufficiency of the FPL tendon channel, impairment of the superficial or deep flexor tendon of the ring finger, limited passive motion of the proximal and distal thumb joints, acute local general infection and non-compliance or incapacity of the patient. SURGICAL TECHNIQUE: The surgical technique depends on the necessity of transosseous refixation of the FDS IV at the base of the distal phalanx of the thumb or the possibility of woven sutures through the FPL proximal to the tendon channel. If the tendon channel is intact the distal part of the FPL tendon is shortened to 1 cm, the FDS IV tendon is cut distal to the chiasma of Camper, pulled through the carpal tunnel and moved into the channel of the FPL tendon and fixed transosseously through the base of the distal phalanx of the thumb. If the transection of the FPL tendon is located proximal to the tendon channel and muscle of the FPL is injured, FDS IV tendon will be woven using the Pulvertaft technique through the FPL tendon at the distal forearm. POSTOPERATIVE MANAGEMENT: Postoperative 6 weeks motion of thumb flexion without resistance in relieved position of the thumb through a thermoplast splint and 6 weeks of functional use of the hand with increasing weight bearing. RESULTS: In this study 10 patients with FDS IV transposition to reconstruct an isolated rupture of the FPL tendon could be followed for an average of 4.1 years postoperatively. The active range of motion of the IP joint of the thumb averaged 65° (10-100°), 8/10 patients achieved an equal active and passive range of motion of the IP joint of the thumb, in 2 patients some flexion insufficiency remained, 9 patients could reach the fingertip of the small finger with the thumb and 1 patient lacked 3 mm. Contracture of the proximal thumb joint developed in two patients. After removal of the FDS IV tendon two patients developed contracture of the PIP joint of the ring finger. The grip force was reduced to 81 %, lateral grip to 83 % and pinch grip to 77 %. The DASH score averaged 18 (0-31) and 8/10 patients would choose to undergo this surgery again.