Photogrammetric evaluation of corrective surgery for trigonocephaly.

The aim of this study was to capture preoperative, postoperative, and follow-up head shapes of male trigonocephaly patients who underwent fronto-orbital remodelling (FOR), using three-dimensional (3D) photography. Fifty-seven male infants with metopic synostosis operated on using standardized FOR during a 5-year period were included. All measurements were compared with those of an age-matched healthy control cohort (n = 253 for early postoperative comparison, n = 43 for the 1-year follow-up comparison) to determine the effect of FOR at 14 days and at 1 year post-surgery. Intracranial volume, frontal angle, nasofrontal angle, interfrontoparietal-interparietal ratio, and inter-orbital distances were measured 1 day preoperatively, 14 days and 1 year postoperatively. Mean age at surgery was 9.7 ± 1.1 months. Prior to surgery, boys with metopic synostosis showed a reduced intracranial volume (-7.0%, P < 0.001), frontal angle (-10.2%, P < 0.001), interfrontoparietal-interparietal ratio (-4.9%, P < 0.01), and orbital distances (-6.5%, P < 0.001) compared to the reference group, but values did not differ significantly from the specific control group after surgery (all P> 0.05). This was consistent by the time of the follow-up examination. Corrective surgery should therefore aim to achieve volume expansion and correction of the deformity. Furthermore, 3D photogrammetry provides a valuable alternative to computed tomography scans in the diagnosis of metopic synostosis, significantly reducing the amount of radiation exposure to the brain.

[A man with groin pain]. / Een man met pijn in de lies.

A 78-year-old man was evaluated at the outpatient orthopaedic clinic with progressive pain in the right groin. X-ray revealed osteoarthritis of the right hip and fibrous dysplasia of the proximal femur. Total hip arthroplasty was performed using a cemented long-stem femoral component spanning the entire lesion.

Neck involvement and disease recurrence in adenoid cystic carcinoma of the minor salivary glands: the role of surgery in primary and progressive disease.

The aim of this study was to analyse the rates of metastatic events and clinical outcomes of patients with adenoid cystic carcinoma (ACC) of the minor salivary glands and to critically evaluate the role of surgical therapy. A retrospective cohort study was designed including all patients with ACC of the oral minor salivary glands treated in the study department during the years 2010-2017. Relevant clinicopathological data were analysed to determine factors with an impact on overall survival (OS) and progression-free survival (PFS). Forty-one patients with primary ACC of the oral cavity and the oropharynx were included. Cervical metastases were found in 14 patients (34.1%) and were shown to have a significant negative impact on OS (P=0.009) and PFS (P=0.03). Sixteen patients developed disease recurrence during follow-up (39.0%) and most patients exhibited local disease recurrence with or without regional or distant metastases (14/16, 87.5%). Local recurrence was treated successfully with surgery in five cases. We recommend surgical therapy for patients with ACC of the minor salivary glands, including elective neck dissection and microvascular reconstruction, to optimize the planning of adjuvant therapy.

The prognostic significance of the lymph node ratio in oral cancer differs for anatomical subsites.

The aim of this study was to validate the prognostic significance of the lymph node ratio (LNR) in patients suffering from oral squamous cell carcinoma in regard to different anatomical subsites. A cohort of 430 patients was investigated to determine the rates of primary metastasis and local and regional disease recurrence. Correlation analysis of the LNR with relevant clinical and pathological parameters was performed. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the prognostic impact for different subsites. Significantly differing rates of primary metastasis and loco-regional disease recurrence were found for cancer of different anatomical subsites of the head and neck. Furthermore, ROC curve analysis suggested that LNR has prognostic relevance in subsets of cancer (tongue, P< 0.001; alveolar process, P= 0.04; maxilla, P= 0.03; buccal mucosa, P= 0.02). The LNR of cancer located in the soft palate (P= 0.6) and floor of the mouth (P= 0.11) showed little or no association with the clinical outcome. There is the need for a more sensitive consideration of the LNR as a factor in the assessment of risk and the treatment decision, as the anatomical subsite plays a crucial role in its impact on the clinical outcome.

First simultaneous detection of helium and tritium inside bubbles in beryllium.

Electron energy loss spectroscopy (EELS) was applied to detect and analyze quantitatively helium (He) and tritium (3H) enclosed inside bubbles in irradiated beryllium. Both gases were formed in beryllium under neutron irradiation as a consequence of neutron-induced transmutation reactions. They were detected for the first time as pronounced peaks at 13.0 eV for 3H and 22.4 eV for He in EELS spectra collected from flat hexagonal bubbles. An adhesion of 3H or formation of thin beryllium hydride layers on the internal basal surfaces was observed. The number densities of both gases were estimated using electron scattering cross-section and intensities obtained from EELS spectra. The number density values estimated for various bubbles fluctuate from 4 to 15 at/nm3 for He and from 4 to 10 molecules/nm3 for 3H2. Lower gas number density was measured inside large bubbles. The observed higher density of tritium at inner walls of bubbles seems to confirm very recent ab initio calculations of the interaction of hydrogen isotopes with beryllium surfaces.

Relations between mandible-only advancement surgery, the extent of the posterior airway space, and the position of the hyoid bone in Class II patients: a three-dimensional analysis.

The objective of the present study was to evaluate the relation between mandibular advancement, the three-dimensional extent of the posterior airway space (PAS), and the position of the hyoid bone, using cone-beam computed tomography (CT). Twenty-eight Class II patients (21 women (mean (SD) age 29 (9) years) and seven men (mean (SD) age 23 (6) years)), who had had mandibular-only advancement surgery (Obwegeser-Dal Pont) were included in the study. In each case, cone-beam CT scans were taken one week before and six months after operation, and a retrospective analysis made of the alterations of several airway variables (volume, mean cross-sectional area, and diameter) and the three-dimensional extent of mandibular and hyoid movement, by using IPlan® cranial software. A linear regression was also done to correlate mandibular advancement, the movement of the hyoid bone, and airway variables. There were significant postoperative increases in all volumetric PAS variables, and in most diametric and spherical variables (p<0.05). There was also a significant linear relation between forward displacement of the mandible and the movement of the hyoid bone (p<0.05). These results show that mandible-only advancement surgery causes an increase in most dimensions of the PAS. This intervention can be assumed to reduce airway resistance and therefore might be a suitable treatment option for patients with obstructive sleep apnoea syndrome.

Long-term donor site morbidity in head and neck cancer patients and its impact on quality of life: a cross-sectional study.

Modern head and neck reconstructive surgery offers a multitude of different reconstructive options. In such cases, donor site morbidity is an important factor in the affected patient's decision-making. The aim of this study was to perform an objective comparison of donor site morbidity for the five most frequent microvascular donor sites in head and neck reconstructive surgery (radial forearm, anterolateral thigh, fibula, iliac crest, and scapula) using a uniform testing system. In this cross-sectional study, 117 donor sites were analyzed (106 for malignant disease and 11 for non-malignant disease): 73 radial forearm, 14 scapula, 12 anterolateral thigh, 10 fibula, and eight iliac crest. Testing consisted of range of motion, muscle strength, and sensation. The non-affected side served as the control. Quality of life was assessed using the Washington Quality of Life Questionnaire version 4 in its German translation. Range of motion was restricted in 15 cases (12.8%). Muscle strength was decreased in 58 cases (49.6%). Sensation was reduced in 70 cases (60%). Concerning quality of life, 31.2% of patients were limited in their daily activities. The scapula flap showed the highest incidence of overall donor site morbidity. However, correlation between objective and subjective donor site impairment was weak and the majority of patients experienced only minor limitations.

The impact of a cervical dysplasia diagnosis on individual cancer prevention habits over time: a bicentric case-control study.

PURPOSE: Annual cervical cancer screening is recommended in Germany as a part of the statutory preventive care. Abnormal results can provoke psychological distress and anxiety, compromising women's adherence. Little is known about how a cervical dysplasia impacts adherence follow-up visits and prevention habits over time. To optimize care strategies, this study aims to identify women at risk for nonadherence to follow-up visits after a screening event. METHODS: Between November 2015 and May 2017, participants with an abnormal Pap smear at the Heidelberg and Leipzig University Hospitals received a four-part questionnaire (sociodemographic data, PHQ-D, self-designed fear and prevention habit questions) at the first consultation (T1) and subsequently after 3 (T2) and 6 (T3) months; healthy controls completed the questionnaire at T1. RESULTS: 132 women with an abnormal Pap smear [with conization: S1 (n = 68, 51.5%), without intervention: S2 (n = 64, 48.5%)] and healthy controls (K, n = 101) generally adhered to gynecological checkups, except S1 6 months after the first diagnosis (S1/T3 - 0.47, signed rank p < 0.0005). Knowledge of primary prevention information, i.e., HPV vaccination, was significantly higher among K (K 58%, S1 29%, S2 44%, Chi-squared p = 0.01) as was vaccine uptake (K 39% versus S1/S2 7% and 17%, respectively, Chi-squared p = 0.0004). Fear of upcoming Pap smears rose significantly over time (S1/T1-S1/T2-S1/T3, Wilcoxon signed-rank test p < 0.001) and was higher among those with conization at T2 (Chi-square test, p = 0.01) and partially accompanied by panic disorders at T1 (Chi-square test p = 0.035). Realization of general preventive habits rose significantly among women without an operative procedure (S2) over the study. CONCLUSION: This study advances the understanding of non-participation in follow-up visits after a dysplasia diagnosis, identifying post-conization women as a special risk group for decreased adherence.

Toward genome editing in X-linked RP-development of a mouse model with specific treatment relevant features.

Genome editing represents a powerful tool to treat inherited disorders. Highly specific endonucleases induce a DNA double strand break near the mutant site, which is subsequently repaired by cellular DNA repair mechanisms that involve the presence of a wild type template DNA. In vivo applications of this strategy are still rare, in part due to the absence of appropriate animal models carrying human disease mutations and knowledge of the efficient targeting of endonucleases. Here we report the generation and characterization of a new mouse model for X-linked retinitis pigmentosa (XLRP) carrying a point mutation in the mutational hotspot exon ORF15 of the RPGR gene as well as a recognition site for the homing endonuclease I-SceI. Presence of the genomic modifications was verified at the RNA and protein levels. The mutant protein was observed at low levels. Optical coherence tomography studies revealed a slowly progressive retinal degeneration with photoreceptor loss starting at 9 months of age, paralleling the onset of functional deficits as seen in the electroretinogram. Early changes to the outer retinal bands can be used as biomarker during treatment applications. We further show for the first time efficient targeting using the I-SceI enzyme at the genomic locus in a proof of concept in photoreceptors following adeno-associated virus mediated gene transfer in vivo. Taken together, our studies not only provide a human-XLRP disease model but also act as a platform to design genome editing technology for retinal degenerative diseases using the currently available endonucleases.

Germline mutation p.N363K in POLE is associated with an increased risk of colorectal cancer and giant cell glioblastoma.

Germline mutations of the POLE gene are responsible for polymerase proofreading-associated polyposis syndrome (PPAP). These mutations were hypothesised to predispose to extra-gastrointestinal tumours (ovary, endometrium, brain), but this association has not been confirmed so far. We report a family with an autosomal dominant inheritance of PPAP due to a c.1089C>A; p.Asn363Lys mutation in the proofreading exonuclease domain of POLE. Ten patients presenting a history of colorectal tumours and three patients with polyposis are indexed in this family. Three carriers (including siblings and a distant cousin at 30, 45 and 52 respectively) and another member (at 37 not tested) presented glioblastoma. This is the second family reported to carry this mutation. Among the four glioblastomas in the family that we report, both show similar pathology: giant cell glioblastoma. These cases suggest that the c.1089C>A germline POLE mutation may confer an increased risk of brain cancer [incidence 17.4% (4/23) in mutation carriers combining the two families]. More observations are needed to support this hypothesis. It seems that not all mutations of POLE are equally associated with extra-gastrointestinal tumours. Although carriers of a mutation responsible for PPAP should benefit from screening for colorectal and uterine cancer, due to the rapid evolution of glioblastoma the value of neurological follow-up and brain imaging screening remains questionable. Nevertheless, considering the limitations of standard therapy for glioblastoma, mutation status could be useful for targeting therapy. The biological mechanism linking POLE mutation to glioblastoma remains to be determined.

Visceral artery aneurysms.

Visceral artery aneurysms are rare with an incidence of only 0.01-0.1% of the population. Open surgical or endovascular elimination should be performed for aneurysms greater than 2 cm in size. The risk of aneurysm rupture is then approximately 25-40%. If the aneurysm ruptures the mortality can be as high as 76%. For mycotic aneurysms or spurious aneurysms there is no lower limit to the diameter size for the need of treatment. Sudden abdominal pain during pregnancy can be caused by visceral artery aneurysms and must be further clarified. The indications for surgery during pregnancy should be made generously. The clinical symptoms (abdominal complaints) of visceral artery aneurysms are manifold. The treatment can be either an open surgical approach or endovascular treatment. In the emergency setting, if endovascular treatment is no longer possible, an open surgical treatment needs to be performed. There are so far no randomized studies which could identify one of the procedures (open surgery vs. endovascular surgery) as clearly being superior. The prognosis after treatment is satisfactory with a 5-10 year survival rate of approximately 90%.

Altered density, composition and microanatomical distribution of infiltrating immune cells in cutaneous squamous cell carcinoma of organ transplant recipients.

BACKGROUND: The inflammatory tumour microenvironment is crucial for effective tumour control, and long-term immunosuppression has been identified as a major risk factor for skin carcinogenesis. In solid organ transplant recipients (OTRs) undergoing long-term pharmacological immunosuppression, an increased incidence of cutaneous squamous cell carcinoma (SCC) and more aggressive tumour growth compared with immunocompetent patients has been reported. OBJECTIVES: To determine the density and phenotype of immune cells infiltrating SCC and surrounding skin in OTRs, and to characterize the microanatomical distribution patterns in comparison with immunocompetent patients. METHODS: We analysed immune cell infiltrates within SCC and at defined regions of interest (ROIs) of tumour-surrounding skin in formalin-fixed paraffin-embedded tissue of 20 renal transplant patients and 18 carefully matched immunocompetent patients by high-resolution semiautomated microscopy on complete tissue sections stained for CD4, CD8, CD20 and CD68. RESULTS: The overall immune cell density of SCC arising in OTRs was significantly reduced compared with immunocompetent patients. Particularly CD4+ infiltrates at the directly invasive margin and tumour vicinity, intratumoral CD8+ T-cell densities and the overall density of CD20+ tumour-infiltrating B cells were significantly reduced in the tissue of OTRs. CONCLUSIONS: Immune cell infiltrates within SCC and at defined ROIs of tumour-surrounding skin in OTRs differ markedly in their composition and microanatomical distribution compared with tumours arising in immunocompetent patients. Our findings substantially broaden the understanding of how long-term systemic immunosuppression modulates the local inflammatory microenvironment in the skin and at the site of invasive SCC.

Dimethyl fumarate modulates neutrophil extracellular trap formation in a glutathione- and superoxide-dependent manner.

BACKGROUND: Neutrophil (polymorphonuclear) granulocytes (PMN) have been shown to contribute to the pathogenesis of psoriasis by releasing interleukin-17 and LL37-DNA complexes via neutrophil extracellular traps (NETs), webs of chromatin strands decorated with antimicrobial peptides, in psoriatic skin. Fumaderm® , a fumaric acid ester (FAE) formulation consisting of different FAE salts, has been successfully used to treat psoriasis for decades. Most recently, FAE treatment was reported to inhibit NET formation in murine epidermolysis bullosa acquisita. OBJECTIVES: To elucidate the effect of FAE treatment on human psoriasis and healthy donor NET formation. RESULTS: Among the compounds present in the FAE formulation, dimethyl fumarate (DMF) pretreatment of human psoriasis and healthy donor PMN resulted in a consistent inhibitory effect on NET formation in response to phorbol 12-myristate 13-acetate but not to platelet activating factor and ionomycin. This effect was l-glutathione (GSH) dependent and involved a decrease in reactive oxygen species (ROS) production, a key event in NET formation. In contrast, G-protein-coupled signalling and protein synthesis were not involved. Monomethyl fumarate (MMF) was found to slightly reduce ROS production without affecting NET formation. CONCLUSIONS: We report DMF as a potent, stimulus-specific, GSH- and ROS-dependent modulator of NET formation. Our results support the notion that modulation of NET formation contributes to the beneficial effects of FAEs in a variety of inflammatory conditions.

Protective regulation of the ACE2/ACE gene expression by estrogen in human atrial tissue from elderly men.

Data from animal experiments and clinical investigations suggest that components of the renin-angiotensin system are markedly affected by sex hormones. However, whether estrogen affects human atrial myocardium has not been investigated yet. In this study, we determined the effects of estrogen on key components of atrial renin-angiotensin system: angiotensin-converting enzyme, responsible for generation of angiotensin II and angiotensin-converting enzyme 2, counteracting majority of AngII effects, and different renin-angiotensin system receptors, AT1R, AT2R, and MAS. First, the expression levels of estrogen receptors mRNA were determined in right atrial appendages obtained from patients undergoing heart surgery. The amounts of estrogen receptor α and estrogen receptor ß mRNA were similar between women ( n = 14) and men ( n = 10). Atrial tissue slices (350 µm) were prepared from male donors which were exposed to estrogen (1-100 nM; n = 21) or stimulated at 4 Hz for 24 h in the presence or absence of 100 nM estrogen ( n = 16), respectively. The administration of estrogen did not change mRNA levels of estrogen receptors, but activated MAP kinases, Erk1/2. Furthermore, estrogen increased the amounts of angiotensin-converting enzyme 2-mRNA (1.89 ± 0.23; P < 0.05) but reduced that of angiotensin-converting enzyme-mRNA (0.78 ± 0.07, P < 0.05). In addition, the transcript levels of AT2R and MAS were upregulated by estrogen. Pacing of tissue slices significantly increased the angiotensin-converting enzyme/angiotensin-converting enzyme 2 ratio at both the mRNA and protein level. During pacing, administration of estrogen substantially lowered the angiotensin-converting enzyme/angiotensin-converting enzyme 2 ratio at the transcript (0.92 ± 0.21 vs. 2.12 ± 0.27 at 4 Hz) and protein level (0.94 ± 0.20 vs. 2.14 ± 0.3 at 4 Hz). Moreover, estrogen elicited anti-inflammatory and anti-oxidative effects on renin-angiotensin system-associated downstream effectors such as pro-oxidative LOX-1 and pro-inflammatory ICAM-1. An antagonist of estrogen receptor α reversed these anti-inflammatory and anti-oxidative effects of estrogen significantly. Overall, our results demonstrated that estrogen modifies the local renin-angiotensin system homeostasis and achieves protective effects in atrial myocardium from elderly men. Impact statement The present study demonstrates that estrogen affects the human atrial myocardium and mediates protective actions through estrogen receptors-(ER) dependent signaling. Estrogen substantially modulates the local RAS via downregulation of ACE and simultaneous upregulation of ACE2, AT2R and MAS expression levels. This is indicative of a shift of the classical RAS/ACE axis to the alternative, protective RAS/ACE2 axis. In support of this view, estrogen attenuated the expression of RAS-associated downstream effectors, LOX-1, and ICAM-1. A specific antagonist of ERα reversed the anti-inflammatory and anti-oxidative effects of estrogen in paced and non-paced atrial tissue slices. In summary, our data demonstrate the existence of protective effects of estrogen in atrial tissue from elderly men which are at least in part, mediated by the regulation of local RAS homeostasis.

[The significance of biofilm for the treatment of infections in orthopedic surgery : 2017 Update]. / Bedeutung des Biofilms für die Infektbehandlung in der Unfallchirurgie : Update 2017.

BACKGROUND: The increase in endoprosthetic and osteosynthetic surgical treatment is associated with a simultaneous increase in implant-associated infections (surgical site infections, SSI). Biofilms appear to play a significant role in the diagnosis and treatment of these infections and heavily contaminated wounds. This article aims to provide a current overview of biofilm and its relevance in orthopedic surgery. MATERIALS AND METHODS: A computer-assisted literature search of MedLine (PubMed) was performed using key word combinations with "biofilm" (as of March 2017). RESULTS: Biofilm, a polymicrobial organization and life form surrounded by a polysaccharide matrix, refers to an adaptation strategy of bacteria in unfavorable living conditions (e. g. under antibiotic therapy). Biofilms can develop after 6 h in highly contaminated wounds. In acute and chronic infections, biofilms can occur in 30-80 % of the cases. Only planktonic bacteria (high metabolic activity, cultivable) can be detected in standard microbiological cultures, biofilms, however, cannot. Molecular microscopic methods, such as fluorescence in situ hybridization (FISH), enable the detection of bacteria in biofilms. The core concepts of anti-biofilm therapy include the prevention of biofilm and early surgical debridement, followed by the local and/or systemic administration of antibiotics as well as the local application of antiseptics. CONCLUSIONS: The development of biofilm should be anticipated in strongly contaminated wounds as well as in acute and chronic infection sites. The best strategy to combat biofilms is to prevent their development. Standard microbiological culture methods do not enable the detection of biofilm. Therefore, the implementation of molecular biological detection methods (z. B. FISH) is important. Further anti-biofilm strategies are being investigated experimentally, but there are no real options for clinical use as of yet.

[Management of lymphatic fistulas in the groin from a surgeon's perspective]. / Management von Lymphfisteln in der Leistenregion aus chirurgischer Sicht.

BACKGROUND: The postoperative occurrence of lymph fistulas in the groin is a complication that should be taken seriously. These fistulas cause an increase in morbidity and can support local and ascending infections. The treatment of this complication ranges from conservative procedures, such as compression dressings and bed rest to operative treatment with detection of the fistulas and ligation, negative pressure wound therapy (NPWT) or even muscle flaps. This review provides an overview of current therapeutic modalities. MATERIAL AND METHODS: On the basis of a current literature search via PubMed, we identified possible treatment options, which are described in this article. RESULTS: The conservative treatment options presented still have an importance in treating groin fistulas. A selection of safe and effective interventional and operative treatments is presented. CONCLUSION: If there are indications for an interventional or operative treatment a variety of safe and effective therapies are available, which can significantly reduce the length of hospital stay. The option of treatment using a muscle flap is of value as a last resort in the treatment of infected vascular prosthesis in the groin of Szilagyi type III and should be used when necessary.

Evaluation of transmit efficiency and SAR for a tight fit transceiver human head phased array at 9.4 T.

Ultra-high field (UHF, ≥7 T) tight fit transceiver phased arrays improve transmit (Tx) efficiency (B1+ /√P) in comparison with Tx-only arrays, which are usually larger to fit receive (Rx)-only arrays inside. One of the major problems limiting applications of tight fit arrays at UHFs is the anticipated increase of local tissue heating, which is commonly evaluated by the local specific absorption rate (SAR). To investigate the tradeoff between Tx efficiency and SAR when a tight fit UHF human head transceiver phased array is used instead of a Tx-only/Rx-only RF system, a single-row eight-element prototype of a 400 MHz transceiver head phased array was constructed. The Tx efficiency and SAR of the array were evaluated and compared with that of a larger Tx-only array, which could also be used in combination with an 18-channel Rx-only array. Data were acquired on the Siemens Magnetom whole body 9.4 T human MRI system. Depending on the head size, positioning and the RF shim strategy, the smaller array provides from 11 to 23% higher Tx efficiency. In general, the Tx performance, evaluated as B1+ /√SAR, i.e. the safety excitation efficiency (SEE), is also not compromised. The two arrays provide very similar SEEs evaluated over 1000 random RF shim sets. We demonstrated that, in general, the tight fit transceiver array improves Tx performance without compromising SEE. However, in specific cases, the SEE value may vary, favoring one of the arrays, and therefore must be carefully evaluated.