Florian S. Frueh

Primary Flexor Tendon Repair in Zones 1 and 2: Early Passive Mobilization Versus Controlled Active Motion

PURPOSE To compare early passive mobilization (EPM) with controlled active motion (CAM) after flexor tendon surgery in zones 1 and 2. METHODS We performed a retrospective analysis of collected data of all patients receiving primary flexor tendon repair in zones 1 and 2 from 2006 to 2011, during which time 228 patients were treated, and 191 patients with 231 injured digits were eligible for study. Exclusion criteria were replantation, finger revascularization, age younger than 16 years, rehabilitation by means other than EPM or CAM, and missing information regarding postoperative rehabilitation. This left 132 patients with 159 injured fingers for analysis. The primary endpoint was the comparison of total active motion (TAM) values 4 and 12 weeks after surgery between the EPM and the CAM protocols. The analysis of TAM measurements under the rehabilitation protocols was conducted using t-tests and further linear modeling. We defined rupture rate and the assessment of adhesion/infection as secondary endpoints. RESULTS There was a statistically significant difference between the TAM values of the EPM and the CAM protocols 4 weeks after surgery. At 12 weeks, however, there was no significant difference between the 2 protocols. Older age and injuries with finger fractures were associated with lower TAM values. Rupture rates were 5% (CAM) and 7% (EPM), which were not statistically different. CONCLUSIONS This study showed a favorable effect of CAM protocol on TAM 4 weeks after surgery. The percent rupture rate was slightly lower in the patients with CAM than in the patients with EPM regime. Further studies are required to confirm our results and to investigate whether faster recovery of TAM is associated with shorter time out of work. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic III.

Current and emerging vascularization strategies in skin tissue engineering

Abstract Vascularization is a key process in skin tissue engineering, determining the biological function of artificial skin implants. Hence, efficient vascularization strategies are a major prerequisite for the safe application of these implants in clinical practice. Current approaches include (i) modification of structural and physicochemical properties of dermal scaffolds, (ii) biological scaffold activation with growth factor-releasing systems or gene vectors, and (iii) generation of prevascularized skin substitutes by seeding scaffolds with vessel-forming cells. These conventional approaches may be further supplemented by emerging strategies, such as transplantation of adipose tissue-derived microvascular fragments, 3D bioprinting and microfluidics, miRNA modulation, cell sheet engineering, and fabrication of photosynthetic scaffolds. The successful translation of these vascularization strategies from bench to bedside may pave the way for a broad clinical implementation of skin tissue engineering.

The hemi-hamate autograft arthroplasty in proximal interphalangeal joint reconstruction: a systematic review:

Palmar lip injuries of the proximal interphalangeal joint with dorsal fracture-dislocation are difficult to treat and often require major reconstruction. A systematic review was performed and yielded 177 articles. Thirteen articles on hemi-hamate autograft were included in full-text analysis. Results of 71 cases were summarized. Mean follow-up was 36 months and mean proximal interphalangeal joint range of motion was 77°. Overall complication rate was around 35%. Up to 50% of the patients showed radiographic signs of osteoarthritis. However, few of those patients complained about pain or impaired finger motion. Based on this systematic analysis and review, hemi-hamate autograft can be considered reliable for the reconstruction of acute and chronic proximal interphalangeal joint fracture-dislocations with joint involvement >50%, but longer-term follow-up studies are required to evaluate its outcome, especially regarding the rate of osteoarthritis. Level of Evidence: II

Adipose Tissue-Derived Microvascular Fragments Improve Vascularization, Lymphangiogenesis, and Integration of Dermal Skin Substitutes

Full-thickness skin defects can be covered with dermal skin substitutes in combination with split-thickness skin grafts. However, slow vascularization of the matrices bears the risk of wound infection and extends the length of hospitalization. To overcome these problems, we describe a promising vascularization strategy. Green fluorescent protein+ adipose tissue-derived microvascular fragments (ad-MVF) were isolated from epididymal fat pads of C57BL/6-Tg(CAG-EGFP)1Osb/J mice. ad-MVF were seeded on collagen-glycosaminoglycan matrices, which were implanted into full-thickness skin defects in the dorsal skinfold chamber of wild-type C57BL/6 mice. Nonseeded matrices served as controls. Vascularization, lymphangiogenesis, and integration of the implants were studied by using intravital fluorescence microscopy, histology, and immunohistochemistry over 14 days. ad-MVF rapidly reassembled into microvascular networks within the implants, which developed interconnections to the host microvasculature. Accordingly, vascularization of the implants was markedly accelerated, as indicated by a significantly higher microvessel density when compared with controls. Moreover, dense lymphatic networks originating from the green fluorescent protein+ ad-MVF developed within the implants. This was associated with an improved implant integration. Hence, seeding ad-MVF on collagen-glycosaminoglycan matrices represents a potential strategy to reduce morbidity and hospitalization of patients undergoing the treatment of full-thickness skin defects.

Animal models in surgical lymphedema research--a systematic review.

BACKGROUND Chronic secondary lymphedema is a well-known complication in oncologic surgery. Autologous lymph node transplantation, lymphovenous anastomosis, and other lymphatic surgeries have been developed in the last decades with rising clinical application. Animal models to explore the pathophysiology of lymphedema and microsurgical interventions have reached great popularity, although the induction of stable lymphedema in animals is still challenging. The aim of this review was to systematically assess lymphedema animal models and their potential use to study surgical interventions. MATERIALS AND METHODS A systematic review according to the PRISMA guidelines was performed without time or language restriction. Studies describing new or partially new models were included in chronological order. Models for primary and secondary lymphedema were assessed, and their potential for surgical procedures was evaluated. RESULTS The systematic search yielded 8590 discrete articles. Of 180 articles included on basis of title, 84 were excluded after abstract review. Ninety-six were included in the final analysis with 24 key articles. CONCLUSIONS No animal model is perfect, and many models show spontaneous lymphedema resolution. The rodent limb appears to be the most eligible animal model for experimental reconstruction of the lymphatic function as it is well accessible for vascularized tissue transfer. There is a need for standardized parameters in experimental lymphedema quantification. Also, more permanent models to study the effect of free vascularized lymph node transfer are needed.

In vivo biocompatibility, vascularization, and incorporation of Integra® dermal regenerative template and flowable wound matrix

Integra® matrix wound dressing (MWD) is used for the reconstruction of full-thickness skin defects. For the treatment of complex wounds, this dermal substitute is available as a flowable wound matrix (FWM) of identical composition. To clarify whether variations in sample preparation and consistency affect the biocompatibility and tissue incorporation, we herein compared MWD and FWM. The matrices were characterized using scanning electron microscopy and histology. Moreover, they were implanted in mouse dorsal skinfold chambers to analyze their in vivo performance over 2 weeks. Scanning electron microscopy showed a planar surface of MWD whereas FWM presented an irregular, fissured morphology. However, histology of the two matrices revealed an identical fiber thickness, fiber length, and interfiber distance. Repetitive stereo-microscopy and immunohistochemical analyses of MWD and FWM showed a comparable epithelialization of the implants in the dorsal skinfold chamber model. At day 14, both matrices exhibited a low collagen content and microvessel density. Moreover, they were infiltrated by a high number of myeloperoxidase (MPO)-positive neutrophilic granulocytes and a lower number of MAC387-positive macrophages and CD3-positive lymphocytes. These findings demonstrate that differences in preparation and consistency do not affect the tissue response to MWD and FWM, indicating a comparable regenerative capacity in wound healing.

Quality of information for women seeking breast augmentation in the Internet.

Abstract Background Recently published data show that many women interested in breast augmentation (BA) actively search the Internet for information. The Internet is currently the main source of information on this topic. Objectives Little is known about the quality of available information on the Internet concerning BA. The goal was to evaluate this in a systematic manner using a validated and reproducible tool. Methods Women (n = 96) unrelated to medicine were asked which keywords they would use to search the Internet if they were interested in BA. Five keywords were used. Qualitative and quantitative assessment was performed with the modified Ensuring Quality Information for Patients (EQIP) tool. A total of 2500 websites containing information on BA were identified using Google, Bing, Yahoo, Ask, and AOL. Results Out of 623 eligible websites, only 153 (25%) addressed more than 20 EQIP items. Scores were higher for encyclopaedias and academic websites compared to hospital and practitioner websites. The median EQIP score was only 15 (IQR = 12–20), and quantitative postoperative morbidity and mortality risk estimates were available in only 38% and 25% of the websites, respectively. Major complications (e.g. capsular contraction, implant safety) were mentioned in only 156 (25%) of the websites. Conclusions This is the first assessment of online patient information on BA using the EQIP tool. This analysis demonstrated several shortcomings in the quality of information provided to BA candidates. There is an immediate need for better informative and educational websites regarding BA procedures that are compatible with international quality standards for plastic surgery.

Carpal tunnel syndrome: Analysis of online patient information with the EQIP tool

Patients suffering from carpal tunnel syndrome (CTS) actively search for medical information on the Internet. The World Wide Web represents the main source of patient information. The aim of this study was to systematically assess the quality of patient information about CTS in the Internet. A qualitative and quantitative assessment of websites was performed with the modified Ensuring Quality Information for Patients (EQIP) tool that contains 36 standardized items. Five hundred websites with information on CTS treatment options were identified through Google, Bing, Yahoo, Ask.com and AOL. Duplicates and irrelevant websites were excluded. One hundred and ten websites were included. Only five websites addressed more than 20 items; quality scores were not significantly different between the various providing groups. A median of 15 EQIP items was found, with the top website addressing 26 out of 36 items. Major complications such as median nerve injury were reported in 27% of the websites and their treatment in only 3%. This analysis revealed several critical shortcomings in the quality of the information provided to patients suffering from CTS. There is a collective need to provide interactive, informative and educational websites for standard procedures in hand surgery. These websites should be compatible with international quality standards for hand surgery procedures.

Isolation of Murine Adipose Tissue-derived Microvascular Fragments as Vascularization Units for Tissue Engineering

A functional microvascular network is of pivotal importance for the survival and integration of engineered tissue constructs. For this purpose, several angiogenic and prevascularization strategies have been established. However, most cell-based approaches include time-consuming in vitro steps for the formation of a microvascular network. Hence, they are not suitable for intraoperative one-step procedures. Adipose tissue-derived microvascular fragments (ad-MVF) represent promising vascularization units. They can be easily isolated from fat tissue and exhibit a functional microvessel morphology. Moreover, they rapidly reassemble into new microvascular networks after in vivo implantation. In addition, ad-MVF have been shown to induce lymphangiogenesis. Finally, they are a rich source of mesenchymal stem cells, which may further contribute to their high vascularization potential. In previous studies we have demonstrated the remarkable vascularization capacity of ad-MVF in engineered bone and skin substitutes. In the present study, we report on a standardized protocol for the enzymatic isolation of ad-MVF from murine fat tissue.

Magnetic Resonance Lymphography at 9.4 T Using a Gadolinium-Based Nanoparticle in Rats: Investigations in Healthy Animals and in a Hindlimb Lymphedema Model

Objectives Magnetic resonance lymphography (MRL) in small animals is a promising but challenging tool in preclinical lymphatic research. In this study, we compared the gadolinium (Gd)-based nanoparticle AGuIX with Gd-DOTA for interstitial MRL in healthy rats and in a chronic rat hindlimb lymphedema model. Materials and Methods A comparative study with AGuIX and Gd-DOTA for interstitial MRL was performed in healthy Lewis rats (n = 6). For this purpose, 75 &mgr;L of 3 mM AGuIX (containing 30 mM Gd-DOTA side residues) and 75 &mgr;L 30 mM Gd-DOTA were injected simultaneously in the right and left hindlimbs. Repetitive high-resolution, 3-dimensional time-of-flight gradient recalled echo MRL sequences were acquired over a period of 90 minutes using a 9.4 T animal scanner. Gadofosveset-enhanced MR angiography and surgical dissection after methylene blue injection served as supportive imaging techniques. In a subsequent proof-of-principle study, AGuIX-based MRL was investigated in a hindlimb model of chronic lymphedema (n = 4). Lymphedema of the right hindlimbs was induced by means of popliteal and inguinal lymphadenectomy and irradiation with 20 Gy. The nonoperated left hindlimbs served as intraindividual controls. Six, 10, and 14 weeks after lymphadenectomy, MRL investigations were performed to objectify lymphatic reorganization. Finally, skin samples of the lymphedematous and the contralateral control hindlimbs were analyzed by means of histology and immunohistochemistry. Results AGuIX-based MRL resulted in high-resolution anatomical depiction of the rodent hindlimb lymphatic system. Signal-to-noise ratio and contrast-to-noise ratio of the popliteal lymph node were increased directly after injection and remained significantly elevated for up to 90 minutes after application. AGuIX provided significantly higher and prolonged signal intensity enhancement as compared with Gd-DOTA. Furthermore, AGuIX-based MRL demonstrated lymphatic regeneration in the histopathologically verified chronic lymphedema model. Collateral lymphatic vessels were detectable 6 weeks after lymphadenectomy. Conclusions This study demonstrates that AGuIX is a suitable contrast agent for preclinical interstitial MRL in rodents. AGuIX yields anatomical imaging of lymphatic vessels with diameters greater than 200 &mgr;m. Moreover, it resides in the lymphatic system for a prolonged time. AGuIX may therefore facilitate high-resolution MRL-based analyses of the lymphatic system in rodents.