Lars Hofmann

Biomechanical and magnetic resonance imaging evaluation of a single- and double-row rotator cuff repair in an in vivo sheep model.

PURPOSE To investigate the biomechanical and magnetic resonance imaging (MRI)-derived morphologic changes between single- and double-row rotator cuff repair at different time points after fixation. METHODS Eighteen mature female sheep were randomly assigned to either a single-row treatment group using arthroscopic Mason-Allen stitches or a double-row treatment group using a combination of arthroscopic Mason-Allen and mattress stitches. Each group was analyzed at 1 of 3 survival points (6 weeks, 12 weeks, and 26 weeks). We evaluated the integrity of the cuff repair using MRI and biomechanical properties using a mechanical testing machine. RESULTS The mean load to failure was significantly higher in the double-row group compared with the single-row group at 6 and 12 weeks (P = .018 and P = .002, respectively). At 26 weeks, the differences were not statistically significant (P = .080). However, the double-row group achieved a mean load to failure similar to that of a healthy infraspinatus tendon, whereas the single-row group reached only 70% of the load of a healthy infraspinatus tendon. No significant morphologic differences were observed based on the MRI results. CONCLUSIONS This study confirms that in an acute repair model, double-row repair may enhance the speed of mechanical recovery of the tendon-bone complex when compared with single-row repair in the early postoperative period. CLINICAL RELEVANCE Double-row rotator cuff repair enables higher mechanical strength that is especially sustained during the early recovery period and may therefore improve clinical outcome.

Molecular genetic analysis of 16 XP‐C patients from Germany: environmental factors predominately contribute to phenotype variations

Patients belonging to xeroderma pigmentosum (XP) complementation group C comprise one‐third of all XP patients. Only four major reports compiled larger groups of XP‐C patients from southern Europe (12 pts), North America (16 pts) and Africa (14 and 56 pts) as well as their genetic background (46 XPC mutations). We identified 16 XP‐C patients from Germany. Interestingly, only five patients exhibited severe sun sensitivity. The mean age of XP diagnosis was 9.4 years, and the median age of the first skin cancer was 7 years. Neurological symptoms were absent in all but two patients. Primary fibroblasts from all 16 patients showed reduced post‐UV cell survival (mean: 50% vs 93% in normal cells) and reduced reactivation of an UV‐treated luciferase reporter gene (mean: 6.4% vs 30.7% in normal cells). XPC mRNA expression was also greatly reduced compared with normal cells (mean: 14.3%; range 8.3–25.7%) except in XP47MA (274.1%). All patients carried homozygous XPC mutations. Four mutations have been described previously: c.1747_1748delTG (found in 4/16), c.567 C>T (4/16), c.1839 C>T (1/16) and a complex insertion/deletion mutation in exon 9 (1/16). The novel frameshift mutations c.446_447delAG (2/16), c.1525insA (1/16) and c.2271delC (1/16) lead to truncated XPC proteins as does the novel nonsense mutation c.843C>T (1/16). XP47MA carries an interesting mutation (c.2538_2540delATC; p.Ile812del) resulting in an in‐frame single amino acid deletion. This mutation results in a classical XP phenotype, a non‐functional XPC protein, but elevated XPC mRNA expression. Our study indicates that extrinsic factors may contribute to XP‐C symptom severity due to nonsense‐mediated message decay.

Functional and molecular genetic analyses of nine newly identified XPD-deficient patients reveal a novel mutation resulting in TTD as well as in XP/CS complex phenotypes

The xeroderma pigmentosum (XP) group D protein is involved in nucleotide excision repair (NER) as well as in basal transcription. Determined by the type of XPD mutation, six different clinical entities have been distinguished: XP, XP with neurological symptoms, trichothiodystrophy (TTD), XP⁄TTD complex, XP⁄Cockayne syndrome (CS) complex or the cerebro‐oculo‐facio‐skeletal syndrome (COFS). We identified nine new XPD‐deficient patients. Their fibroblasts showed reduced post‐UV cell survival, reduced NER capacity, normal XPD mRNA expression and partly reduced XPD protein expression. Six patients exhibited a XP phenotype in accordance with established XP‐causing mutations (c.2079G>A, p.R683Q; c.2078G>T, p.R683W; c.1833G>T, p.R601L; c.1878G>C, p.R616P; c.1878G>A, p.R616Q). One TTD patient was homozygous for the known TTD‐causing mutation p.R722W (c.2195C>T). Two patients were compound heterozygous for a TTD‐causing mutation (c.366G>A, p.R112H) and a novel p.D681H (c.2072G>C) amino acid exchange, but exhibited different TTD and XP/CS complex phenotypes, respectively. Interestingly, the XP/CS patients cells exhibited a reduced but well detectable XPD protein expression compared with hardly detectable XPD expression of the TTD patients cells. Same mutations with different clinical outcomes in NER‐defective patients demonstrate the complexity of phenotype–genotype correlations, for example relating to additional genetic variations (parental consanguinity), different allelic expression due to SNPs or differences in the methylation status.

Reflectance confocal microscopy and Hailey-Hailey disease: assessment of response to treatment after CO2 laser ablation.

Hailey-Hailey disease (familial benign chronic pemphigus) is an autosomal-dominant genodermatosis characterized by erosions, fissures and blistering in intertriginous areas, which is due to a mutation of the ATP2C1 gene on chromosome 3q21–24 that leads to a coding defect of a Ca2+ ATPase of the Golgi apparatus. This results in reduced intracellular Ca2+ levels, insufficient development of Ca-dependent adhesion molecules (E cadherin) on keratinocytes and subsequent acantholysis [1]. Patients often suffer not only from severe itching, burning or pain, but also from frequent secondary infections with Candida or Staphylococci [2]. Topical antimicrobial treatments as well as topical corticosteroids or calcineurin inhibitors are occasionally successful [3]. Other strategies include retinoids [4] or botulinum toxin injections [5]. Dermabrasion and ablative CO2 laser therapy provide surgical alternatives [6, 7]. A 46-year-old man presented with axillary HaileyHailey disease; we were able to document healing of the lesion following CO2 laser ablation using in vivo confocal laser scanning microscopy at high cellular resolution. Histologically we saw typical acantholysis of the granular layer with concomitant structural loosening of the epidermal cells to form the classically described “dilapidated brick wall” [2, 8]. Following only temporarily successful treatments with topical corticosteroids, antibiotics and antimycotics, the patient underwent CO2 laser ablation of the affected areas under local anesthesia (QuadraLASETM Fractional CO2-Laser, Candela Laser GmbH, Neu-Isenburg, Germany; settings: 400 μs impulse duration, 200 Watts, 10 passes). An affected area of the left axilla was evaluated using dermatoscopy, histology and in vivo confocal laser scanning microscopy (VivaScope® 1500/3000, MAVIG GmbH, Munich, Germany) prior to the first treatment (Figure 1) and at four weeks, eight weeks (Figure 2) and eight months (Figure 3) follow-up. Clinically and dermatoscopically, prior to treatment there was severe inflammation (dense polymorphic/diffuse vascular pattern) with numerous erosions (Figure 1a–b). Histological examination confirmed the diagnosis of Hailey-Hailey disease with an acanthotic epidermis (Figure 1c–d) with transepidermal acantholysis and individual dyskeratotic keratinocytes. The neighboring Clinical Letter

Morphologic criteria of vesiculobullous skin disorders by in vivo reflectance confocal microscopy.

Reflectance confocal microscopy (RCM) may be a useful method for accurate, rapid, and noninvasive bedside diagnosis of vesiculobullous skin diseases (VSD). The main outcome measure of this study was a descriptive statistical analysis of RCM features associated with selected group of VSD.

Komplexe operative Therapie multipler Trichoepitheliome

Trichoepitheliome (TE) sind benigne epithelial-mesenchymale Tumoren, welche von Haarfollikeln ausgehen [1]. Sie imponieren gewöhnlich als 2–8 mm (selten bis zu 3 cm) durchmessende, derbe, halbkugelige, hautfarbene Papeln oder Nodi und können bis tief in die Subkutis reichen. Während solitäre TE bis in das Erwachsenenalter sporadisch am gesamten Integument auftreten können, manifestieren sich multiple TE im Rahmen von Syndromen, beispielsweise der autosomal dominanten Genodermatose multiple familiäre Trichoepitheliome (MFT), bereits in der Kindheit bis frühen Adoleszenz. Bevorzugte Lokalisationen der letzteren Tumoren sind Gesicht (nasolabial, periorbital und periaurikulär), Kopfhaut, Nacken und selten auch der Stamm. Als Ursache wurden sowohl Mutationen im Cylindromatosis-Gen (CYLD1), einem Tumorsuppressor-Gen auf Chromosom 16q12-q13, als auch Clinical Letter auf Chromosom 9p21 beschrieben [2]. Aufgrund einer geringeren Expressivität und Penetranz dieser Mutationen bei Männern sind vor allem Frauen betroffen [3]. Mutationen im CYLD-Gen können Ursache weiterer, klinisch ähnlicher autosomal dominanter Syndrome sein. Während bei der familiären Zylindromatose ausschließlich Zylindrome auftreten, geht das Brooke-Spiegler-Syndrom mit TE, Zylindromen und Spiradenomen einher [4]. Die Ausbildung dieser Tumoren vor allem im Kopfund Halsbereich stellt ein ästhetisches Problem dar, welches psychologische Beeinträchtigung und sozialen Rückzug zur Folge haben kann.

Complex surgical therapy of multiple trichoepitheliomas

Trichoepitheliomas (TEs) are benign epithelial and mesenchymal tumors arising from hair follicles [1]. They usually appear as firm, hemispherical, skin-colored papules or nodules, usually 2–8 mm in diameter (rarely up to 3 cm), potentially extending deep into the subcutaneous tissue. While solitary TEs can arise sporadically on the entire integument until adulthood, multiple TEs already occur in childhood to early adolescence as part of syndromes, for example, in multiple familial trichoepitheliomas (MFT), an autosomal dominant genodermatosis. Predilection sites of the latter tumors are the face (nasolabial, periorbital, and periauricular), scalp, neck, and rarely also the trunk. The condition is caused by mutations in the cylindromatosis gene (CYLD1), a tumor suppressor gene on chromosome 16q12-q13, and also on chromosome 9p21 [2]. The disease primarily affects women due to lower expressivity and penetrance of these mutations in men [3]. Mutations in the CYLD gene can be the cause of other, clinically similar autosomal dominant syndromes. While familiar cylindromatosis exclusively shows cylindromas, the Brooke-Spiegler syndrome is associated with TEs, cylindromas, and spiradenomas [4]. Development of these tumors especially in the head and neck region is an aesthetic problem, which can result in psychological impairment and social withdrawal.

Rapidly growing blue-red nodule on the cheek of a 4-year-old boy: Case for Diagnosis

Dermatoscopy (Handyscope for iPhone 4, FotoFinder Systems, Bad Birnbach, Germany) revealed a sharply demarcated, symmetric, round tumor with diffuse blue to bluish-red pigmentation (Figure 1c). Macroscopically visible telangiectases disappeared upon compression by the dermatoscopic contact plate. A few lightly colored streaks were visible. Rapidly growing blue-red nodule on the cheek of a 4-year-old boy Case for Diagnosis

Rapidly growing blue-red nodule on the cheek of a 4-year-old boy. Pilomatricoma.

Dermatoscopy (Handyscope for iPhone 4, FotoFinder Systems, Bad Birnbach, Germany) revealed a sharply demarcated, symmetric, round tumor with diffuse blue to bluish-red pigmentation (Figure 1c). Macroscopically visible telangiectases disappeared upon compression by the dermatoscopic contact plate. A few lightly colored streaks were visible. Rapidly growing blue-red nodule on the cheek of a 4-year-old boy Case for Diagnosis

Rapidly growing blue‐red nodule on the cheek of a 4‐year‐old boy

Dermatoscopy (Handyscope for iPhone 4, FotoFinder Systems, Bad Birnbach, Germany) revealed a sharply demarcated, symmetric, round tumor with diffuse blue to bluish-red pigmentation (Figure 1c). Macroscopically visible telangiectases disappeared upon compression by the dermatoscopic contact plate. A few lightly colored streaks were visible. Rapidly growing blue-red nodule on the cheek of a 4-year-old boy Case for Diagnosis