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.

Inflation of 430-parsec bipolar radio bubbles in the Galactic Centre by an energetic event.

The Galactic Centre contains a supermassive black hole with a mass of four million Suns1 within an environment that differs markedly from that of the Galactic disk. Although the black hole is essentially quiescent in the broader context of active galactic nuclei, X-ray observations have provided evidence for energetic outbursts from its surroundings2. Also, although the levels of star formation in the Galactic Centre have been approximately constant over the past few hundred million years, there is evidence of increased short-duration bursts3, strongly influenced by the interaction of the black hole with the enhanced gas density present within the ring-like central molecular zone4 at Galactic longitude |l| < 0.7 degrees and latitude |b| < 0.2 degrees. The inner 200-parsec region is characterized by large amounts of warm molecular gas5, a high cosmic-ray ionization rate6, unusual gas chemistry, enhanced synchrotron emission7,8, and a multitude of radio-emitting magnetized filaments9, the origin of which has not been established. Here we report radio imaging that reveals a bipolar bubble structure, with an overall span of 1 degree by 3 degrees (140 parsecs × 430 parsecs), extending above and below the Galactic plane and apparently associated with the Galactic Centre. The structure is edge-brightened and bounded, with symmetry implying creation by an energetic event in the Galactic Centre. We estimate the age of the bubbles to be a few million years, with a total energy of 7 × 1052 ergs. We postulate that the progenitor event was a major contributor to the increased cosmic-ray density in the Galactic Centre, and is in turn the principal source of the relativistic particles required to power the synchrotron emission of the radio filaments within and in the vicinity of the bubble cavities.

Intracranial volume (ICV) in isolated sagittal craniosynostosis measured by 3D photocephalometry: A new perspective on a controversial issue.

BACKGROUND: There are still controversies regarding the intracranial volumes in patients with isolated sagittal craniosynostosis compared to a healthy population. This study aimed to compare the intracranial volume of children with sagittal synostosis and scaphocephaly to an age- and gender-matched control cohort using three-dimensional (3D) photogrammetry. METHODS: 62 boys and nine girls with sagittal craniosynostosis were included in this study. The intracranial volume was measured at the first clinical presentation. However, 3D photogrammetry was performed at children not younger than 3 months. The 3D photogrammetric data of 547 healthy boys and 287 healthy girls between the ages of 3-10 month was analyzed to establish an age- and gender-matched control group. RESULTS: Male patients with sagittal synostosis showed a significantly reduced intracranial volume compared to the reference group. For female patients, the intracranial volume was slightly lower compared to the norm group, but not significantly. CONCLUSIONS: Male children with sagittal synostosis showed significantly decreased intracranial volume between the age of 3 and 10 months compared to an age- and gender-matched control group. Female patients in the same age group presented a lower intracranial volume compared to the norm group. Measuring intracranial volume using 3D photogrammetry is a comparable and valuable alternative to CT scans that leads to a significant reduction of radiation exposure to the growing brain.

Regeneration of the intestinal mucosa in Eimeria and E. Coli challenged broilers supplemented with amino acids.

The aim of this study was to evaluate the regeneration of the intestinal mucosa in Eimeria and E. coli challenged broilers supplemented with glutamine, arginine, and threonine. Six hundred male broilers at one d of age from the Cobb strain were utilized. The design was completely randomized using a 2×3 factorial design (unchallenged and challenged and 3 diets). A commercial diet was used as a control and 2 other diets were formulated with glutamine (1.5 and 3% Aminogut®), arginine (1 and 2% L-Arginine), and threonine (1 and 2% L-threonine). The animals that consumed diets supplemented with amino acids presented better (P<0.05) feed conversion in the period from one to 42 d of age. The ability of cell proliferation and the villus:crypt ratio in response to enteric challenge were greater (P<0.05) for broilers that received diets supplemented with amino acids. High levels of amino acids in the experimental feeds reflected in greater protein levels in poultry house litter, and they did not interfere with ammonia production. The supplementation of diets with trophic amino acids can positively contribute to the regeneration and proliferation of the intestinal mucosa in broilers and to the maintenance of zootechnical performance when submitted to enteric challenges.

Identification of educational needs in the management of overweight and obesity: results of an international survey of attitudes and practice.

Despite the availability of a growing range of interventions to assist control of body weight for people with excess weight or obesity, only a small proportion of people achieve their weight loss goals and are able to maintain body weight reductions in the long term. Negative attitudes and beliefs are often found among physicians and others involved in treating obesity and may adversely impact the effectiveness of management. In this international study, healthcare professionals were invited to complete an online survey of their attitudes and practice in the management of excess body weight. A total of 335 clinicians completed the survey of whom approximately half were based in Europe. A key finding from the survey is that, while participants are generally confident in their ability to manage overweight and obesity effectively, they also report that most of their patients are not successful in achieving their weight loss goals. At the same time, participants tended to overestimate the effectiveness of current medical management in maintaining reductions in body weight. Educational initiatives addressing the real-life effectiveness of different weight control interventions may help to close the gap between clinicians' perceptions and reality in the management of excess body weight.

[The Biological Knife II - Fracture Healing and Pharmacological Interactions]. / Das biologische Skalpell II - Frakturheilung und pharmakologische Einflussfaktoren.

The reasons for delayed fracture healing or non-union formation are multifactorial. Mechanical factors are well known to influence the process of fracture healing. However, there is a lack of knowledge about the biological conditions that have to be achieved for adequate bone healing. Treatment of non-unions is still demanding and we have only poor options to stimulate the bone healing process. Therefore, it is important to optimise the biological conditions to avoid non-union formation. Beside patient-related factors, pharmacological drugs are able to impede or stimulate fracture healing. Especially geriatric patients show a pre-existing drug medication due to different co-morbidities. However, also younger patients are frequently treated with different drugs for infection prophylaxis, analgesia or thrombosis prophylaxis. The aim of the current review article is to give an overview about the influence of different pharmacological agents on the process of fracture healing. A deeper understanding of a drug-related influence on fracture healing could help the medical practitioner to optimise the general conditions for adequate fracture healing, i.e., by avoiding specific pharmacological agents. Vice versa some drugs could be used to stimulate fracture healing in the future.

Preliminary results from a prospective study of laparoscopic aortobifemoral bypass using a clampless and sutureless aortic anastomotic technique.

OBJECTIVE: This prospective study describes the feasibility and safety of a new clampless and sutureless aortic anastomotic technique used during retroperitoneal laparoscopic aortobifemoral bypass in extensive aortoiliac occlusive lesions. This is a case series of a previously published technique, demonstrating wider applicability of the technique. MATERIALS AND METHODS: Twelve patients underwent a clampless and sutureless laparoscopic bypass for TASC D aortoiliac occlusive lesions using the EndoVascular REtroperitoneoScopic Technique (EVREST). Dissection of the retroperitoneal space and the infrarenal aorta was performed laparoscopically. A bifurcated graft was inserted into the retroperitoneal space. The main body of the graft was connected on the left side of the aorta by an intra- and extra-aortic covered stent-graft. An aortic clamp was used temporarily on four patients because of excessive bleeding when the connector was deployed. The femoral anastomoses were performed by classic open surgery. Initial technical success, complications, and bypass patency were assessed. RESULTS: Median follow-up was 9.3 months. Median operative time was 265 minutes. Median duration of aorto-prosthetic connection was 60 seconds. Thirty-day postoperative mortality was 0%. No major postoperative complications were observed. All grafts were patent at the end of follow-up and there was no early or late disruption of the proximal assembly. CONCLUSIONS: EVREST greatly facilitates laparoscopic aortic surgery in occlusive disease with no need for suture or clamping of the aorta. This technique performed in a single center on 12 patients, seems to be feasible and safe. It offers the advantages of laparoscopy and those of endovascular surgery, especially in the challenging conditions encountered during aortic laparoscopic surgery. Early experience supports procedural and initial postprocedural safety and demonstrates proof-of-concept for EVREST.

Treatment and outcomes of Candida osteomyelitis: review of 53 cases from the PATH Alliance® registry.

Candida osteomyelitis is associated with significant morbidity; however, data on the management of Candida osteomyelitis are limited. The Prospective Antifungal Therapy (PATH) Alliance® registry is a comprehensive, multicenter, prospective, observational registry that collected data on patients with invasive fungal infections between 2004 and 2008. The aim of this descriptive analysis was to evaluate the clinical characteristics, treatment, and outcomes of patients with Candida osteomyelitis. Using the PATH Alliance® registry, we performed a review of all patients with a proven diagnosis of Candida osteomyelitis who received a minimum of 14 days of antifungal treatment and/or a therapeutic surgical intervention (n = 53). The epidemiology, diagnosis, treatment, and outcomes of these patients were assessed at 12 weeks. C. albicans (56.6 %) was the most commonly identified organism, followed by C. parapsilosis (18.9 %), C. glabrata (9.4 %), and C. tropicalis (9.4 %). The mean treatment duration was 54.9 days. Multiple different treatment regimens were administered to patients. These included fluconazole (56.0 %), echinocandins (29.3 %), amphotericin B formulations (10.7 %), and voriconazole (4.0 %). Twenty-eight patients (52.8 %) also had a therapeutic surgical intervention. Clinical response was improved in 38 (71.7 %) patients (43.4 % complete and 28.3 % partial response), stable in 11 (20.8 %), and worse in one (1.9 %); three (5.7 %) patients had unknown response. The 12-week survival rate was 93.8 %. In summary, C. albicans was the predominant pathogen, and fluconazole was the most commonly administered agent. However, treatment patterns vary and remain non-standardized. Concurrent candidemia was infrequent, and 12-week survival was notably good in this series of 53 patients with Candida osteomyelitis.

Local cortical thinning links to resting-state disconnectivity in major depressive disorder.

BACKGROUND: Local structural and metabolic as well as inter-regional connectivity abnormalities have been implicated in the neuropathology of major depressive disorder (MDD). How local tissue properties affect intrinsic functional connectivity is, however, unclear. Using a cross-sectional, multi-modal imaging approach, we investigated the relationship between local cortical tissue abnormalities and intrinsic resting-state functional connectivity (RSFC) in MDD. METHOD: A total of 20 MDD in-patients and 20 healthy controls underwent magnetic resonance imaging at 3 T for structural and functional imaging. Whole-brain cortical thickness was calculated and compared between groups. Regions with reduced cortical thickness defined seeds for subsequent whole-brain RSFC analyses. Contributions of structural tissue abnormalities on inter-regional RSFC were explicitly investigated. RESULTS: Lower cortical thickness was observed in MDD in the right dorsomedial prefrontal cortex (PFC), superior temporal gyrus/temporal pole, middle-posterior cingulate cortex, and dorsolateral PFC. No differences in local fractional amplitude of low-frequency fluctuations were observed. Lower thickness in patients' dorsomedial PFC further directly and selectively affected its RSFC with the precuneus, which was unaffected by symptom severity. No effects of cortical thickness in other regions showing abnormal thickness were observed to influence functional connectivity. CONCLUSIONS: Abnormal cortical thickness in the dorsomedial PFC in MDD patients was observed to selectively and directly affect its intrinsic connectivity with the precuneus in MDD patients independent of depression severity, thereby marking a potential vulnerability for maladaptive mood regulation. Future studies should include an unmedicated sample and replicate findings using independent component analysis to test for morphometric effects on network integrity.

Novel mutations of the PRKAR1A gene in patients with acrodysostosis.

Acrodysostosis is characterized by a peripheral dysostosis that is accompanied by short stature, midface hypoplasia, and developmental delay. Recently, it was shown that heterozygous point mutations in the PRKAR1A gene cause acrodysostosis with hormone resistance. By mutational analysis of the PRKAR1A gene we detected four different mutations (p.Arg368Stop, p.Ala213Thr, p.Tyr373Cys, and p.Arg335Cys) in four of seven affected patients with acrodysostosis. The combination of clinical results, endocrinological parameters and in silico mutation analysis gives evidence to suppose a pathogenic effect of each mutation. This assumption is supported by the de novo origin of these mutations. Apart from typical radiological abnormalities of the hand bones, elevated thyroid stimulating hormone and parathyroid hormone values as well as short stature are the most common findings. Less frequent features are characteristic facial dysmorphisms, sensorineural hearing loss and mild intellectual disability. These results lead to the conclusion that mutations of PKRAR1A are the major molecular cause for acrodysostosis with endocrinological abnormalities. In addition, in our cohort of 44 patients affected with brachydactyly type E (BDE) we detected only one sequence variant of PRKAR1A (p.Asp227Asn) with an unclear effect on protein function. Thus, we conclude that PRKAR1A mutations may play no major role in the pathogenesis of BDE.

Ruptured aneurysm of the popliteal artery. Is the diagnosis still difficult?

The aneurysm of the popliteal artery is the most commonly treated non-aortoiliac aneurysm, accounting for more than 70% of all peripheral aneurysms. The rupture of a popliteal aneurysm is rare and it is often misdiagnosed. In the case of a 46-year old female patient here reported, the patient was referred to our department with the diagnosis of ruptured aneurysm of the right popliteal artery with formation of a large pseudo-aneurysm. We operated the patient on a semi-urgent basis and performed a replacement of the popliteal artery by a saphenous vein graft. Three months after the operation, the patient was free of symptoms. This article's aim was to emphasize on how the pitfalls during clinical examination, as well as the problems of imaging interpretation, can make the diagnosis of ruptured popliteal aneurysm still difficult.

Donor-derived transplant acceptance-inducing cells in composite tissue allotransplantation.

BACKGROUND: Composite tissue allotransplantation (CTA) is a newly emerging field of transplantation. Immunological research in CTA has been intensified due to the recent clinical success of hand and face transplantation. Establishing immunological tolerance by adoptive transfer of ex vivo cultured tolerance-inducing cell types is of growing interest. Transplant acceptance-inducing cells (TAICs) are a type of deactivated immunoregulatory macrophages. METHODS: A total of 36 allogeneic hind limb transplantations in the rat were performed in six groups. Group A (Lewis (LW) â†’ Brown-Norway (BN)) received Lewis-donor-derived TAICs locally (i.m.). Group B (LW â†’ BN) received Lewis-donor-derived TAICs systemically (i.v.) and group C (Sprague Dawley (Sp-D) â†’ BN) served as a control group receiving Lewis-donor-derived TAICs systemically (i.v.). Groups D (LW â†’ BN), E (LW â†’ BN), and F (BN â†’ BN) also served as control groups with group D receiving no immunosuppression, group E receiving FK506 and prednisolone and group F receiving no immunosuppression with isograft transplantations (BN â†’ BN). The timing of rejection was assessed by clinical observation and histological findings. RESULTS: Rejection of the allogeneic hind limb occurred on average 7.7 days after transplantation in group A and 7.4 days in group B. Rejection was significantly delayed (Log-rank test, p < 0.01) compared to groups C and D, where rejection of the allogeneic hind limb occurred on average 5.8 days and 5.6 days after transplantation. No rejection was seen in groups E and F. CONCLUSION: For the first time, TAICs have been applied in a CTA model and demonstrated a significant immunosuppressive effect. Even though the immunomodulatory effect is relatively modest, the results of this study justify subsequent research on TAIC therapy to improve experimental and clinical outcome after CTA.

Mild to Moderate Intellectual Disability and Significant Speech and Language Deficits in Patients with FOXP1 Deletions and Mutations.

Very recently, FOXP1 deficiency was shown to result in a phenotype of intellectual disability with significant speech and language impairment. Behavioral abnormalities should be considered as part of the clinical spectrum. Mild craniofacial abnormalities found in half of the described patients expand the clinical spectrum associated with FOXP1 mutations.

BRCA1/2 testing: uptake, phenocopies, and strategies to improve detection rates in initially negative families.

In families with clustering of breast and ovarian cancer, molecular testing of the major susceptibility genes BRCA1/2 helps to identify patients with disease mutations and healthy persons at high risk who can participate in targeted intervention programs. We investigated 5559 families from the German Consortium for Hereditary Breast and Ovarian Cancer included between 1997 and 2008 and treated under clinical routine conditions. In each family an index patient/person had been screened for deleterious mutations in BRCA1/2. Healthy relatives agreed to predictive testing in 888 of 1520 BRCA1/2 mutation-positive families (58%). Of 2646 eligible unaffected first-degree relatives 1143 decided to be tested (43%). In 325 families with BRCA1/2-positive index patients one related BC/OC patient was tested and 39 (12.0%; 95% confidence interval: 8.7-16.0%) discrepant cases found. A second related individual was screened in 163 of 3388 (4.9%) families with BRCA1/2-negative index patient and in eight families a BRCA1/2 mutation was found. In BRCA1/2 mutation-positive families, BC/OC patients lacking the familial mutation have to be expected at a rather high rate. In families with BRCA1/2-negative index patient we recommend a second screening if another patient with a high probability of carrying a BRCA1/2 mutation is available.

The management of hypertensive emergencies in children after stem cell transplantation.

AIM OF THE REVIEW: This work presents a short overview on the available data about drugs that are currently used to treat hypertensive emergencies in children with a focus on incidents after stem cell transplantation. It shows that the pediatric use of all hypotensive agents appears to be mainly based on personal experience of the attending physicians rather than on convincing clinical trials. METHOD: A literature search was performed in MEDLINE, through PubMed, using the medical subject headings (MeSH) hypertensive emergencies, nifedipine, nicardipine, and children. Further articles were identified by checking cross-references of articles and books. RESULTS: Hypertensive emergencies in children after stem cell transplantation usually have a renal etiology, because of the treatment with the calcineurin inhibitors cyclosporine and tacrolimus. In these severe cases an immediate action is necessary to avoid possible appearance or exacerbation of endorgan damage. Because of their mechanism of action and a potential nephroprotective effect calcium channel blockers may be particularly suitable in cases of hypertensive emergencies. An intravenous application of nifedipine may compensate the difficulties of accurate dosing, but keeping in mind possible severe side effects and the lack of published experience its use in children is at least questionable. Nicardipine appears to be the hypotensive agent of first choice. In adults, the treatment of hypertensive emergencies with intravenous nicardipine is well-documented, but for an evaluation of safety in pediatric use, the published studies and case reports appear to be barely adequate. CONCLUSION: The actual treatment approaches vary widely, demonstrating the lack of hard science on which current treatment of hypertensive emergencies in children is based. The hypotensive agent for the individual situation should be chosen considering the properties, side effects, the limited experiences with its use and the patient's anamnesis.

Palliative treatment of malignant pleural effusions.

AIM: The aim of the current study was to analyse the results of video assisted thoracoscopic (VATS) talc pleurodesis for malignant pleural effusion. MATERIAL AND METHODS: From January 2002 to December 2004, 50 VATS procedures were performed under general anaesthesia on 48 patients for malignant pleural effusion. There were 45 women and 3 men with a median age of 57 years. The most common primary neoplasms were breast cancer (68%), ovarian cancer (6%), colon cancer (4%) and lung cancer (4%). Five patients had other types of tumour, including malignant lymphoma, fibrosarcoma, renal cell carcinoma, malignant pleural mesothelioma, acute myeloblastic leukaemia. RESULTS: The average duration of the operation was 46 min (range 20-120). Median duration of postoperative drainage was 5 days (range 2-13) and postoperative hospitalisation was 8 days (range 2-13). Four patients had postoperative complications. Thirty-day mortality was 1/48. One patient died from myocardial infarction. Three postoperative complications were noted (one non-septic febrile episode, one bilateral pneumopathy and one transitory hypoxaemia, treated by non invasive ventilation). Patients were relieved from dyspnoea in 34/48 of the cases (71%). Median survival was 6 months (ranging from 14 days to 2 years). CONCLUSIONS: Early talc pleurodesis via VATS is a safe technique for successfully treating pleural effusion and preventing recurrence in palliative patients with a symptomatic malignant pleural effusion.

Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients.

Contemporary epidemiology and outcomes of invasive fungal infections (IFIs) in solid organ transplant (SOT) recipients are not well described. From March 2004 through September 2007, proven and probable IFIs were prospectively identified in 17 transplant centers in the United States. A total 429 adult SOT recipients with 515 IFIs were identified; 362 patients received a single and 67 patients received >or=2 organs. Most IFIs were caused by Candida species (59.0%), followed by Aspergillus species (24.8%), Cryptococcus species (7.0%), and other molds (5.8%). Invasive candidiasis (IC) was the most frequently observed IFI in all groups, except for lung recipients where invasive aspergillosis (IA) was the most common IFI (P<0.0001). Almost half of IC cases in liver, heart, and lung transplant recipients occurred during the first 100 days post transplant. Over half of IA cases in lung recipients occurred >1 year post transplant. Overall 12-week mortality was 29.6%; liver recipients had the highest mortality (P=0.05). Organ damage, neutropenia, and administration of corticosteroids were predictors of death. These results extend our knowledge on the epidemiology of IFI in SOT recipients, emphasizing the occurrence of IC early after non-lung transplant, and late complications with molds after lung transplant. Overall survival appears to have improved compared with historical reports.

First-trimester prenatal diagnosis of Okihiro syndrome.

A case of Okihiro syndrome (OS) detected by 2- and confirmed by 3-dimensional ultrasound at 13+2 gestational weeks is reported. While the pregnant woman affected by the OS presented with limb anomalies, the fetus showed severe thoracoabdominal and skeletal anomalies. Termination of pregnancy was performed at 14+1 gestational weeks and confirmed the sonographically detected symptoms. The diagnosis was confirmed by autoptic, radiologic and molecular genetic analysis. To our knowledge, this is the first case of prenatal diagnosis of OS.