The Association between Tumour Markers and Meta-iodobenzylguanidine Scans in South African Children with High-risk Neuroblastoma.

AIMS: Diagnostic and post-induction 123I-meta-iodobenzylguanidine (123I-mIBG) scans have prognostic significance in the treatment of neuroblastoma, but data from low- and middle-income countries are limited due to resource constraints. The aim of this study was to determine the association between neuroblastoma-associated tumour markers (lactate dehydrogenase [LDH], ferritin and MYCN amplification) and 123I-mIBG scans (modified Curie scores and metastatic disease patterns) in predicting complete metastatic response rates (mCR) and overall survival. MATERIALS AND METHODS: Two hundred and ninety patients diagnosed with high-risk neuroblastoma in South Africa between January 2000 and May 2018 and a subanalysis of 78 patients with diagnostic 123I-mIBG scans were included. Data collection included LDH, ferritin and MYCN amplification at diagnosis. Two nuclear physicians independently determined the modified Curie scores and pattern of distribution for each diagnostic and post-induction 123I-mIBG scans with high inter-rater agreement (r = 0.952) and reliability (K = 0.805). The cut-off values for the diagnostic and post-induction modified Curie scores of ≥7.0 (P = 0.026) and 3 (P = 0.009), respectively, were generated. The association between the tumour markers and the modified Curie score of the 123I-mIBG scans was determined using post-induction mCR and 2-year overall survival. RESULTS: Diagnostic LDH (P < 0.001), ferritin (P < 0.001) and the diagnostic modified Curie scores (P = 0.019) significantly predicted mCR. Only ferritin correlated with diagnostic modified Curie scores (P = 0.003) but had a low correlation coefficient of 0.353. On multivariable analysis, the only significant covariate for 2-year overall survival at diagnosis was LDH <750 U/l (P = 0.024). A post-induction chemotherapy modified Curie score ≤3.0 had a 2-year overall survival of 46.2% compared with 30.8% for a score >3.0 (P = 0.484). CONCLUSION: LDH, ferritin and the diagnostic 123I-mIBG scans significantly predicted mCR, but only LDH predicted 2-year overall survival. Ferritin and the modified Curie scores correlated with each other. MYCN amplification neither correlated with any aspect of the 123I-mIBG scans nor significantly predicted mCR or 2-year overall survival. LDH and ferritin are therefore appropriate neuroblastoma tumour markers to be used in low- and middle-income countries with limited or no access to mIBG scans and/or MYCN amplification studies.

[Treatment-process analysis of orthopaedic trauma surgery patients at an outpatient setting in a university hospital]. / Prozessanalyse der ambulanten Behandlung unfallchirurgischer Patienten an einer universitären Poliklinik.

BACKGROUND: The cost pressure in a competitive environment forces hospitals and physicians to optimize clinical processes. In order to secure competitive advantages, a continuous evaluation of relevant processes is necessary. OBJECTIVE: Administrative and medical processes in a university outpatient department for orthopedics and traumatology were evaluated using the lean method in order to reduce patient waiting times. MATERIAL AND METHODS: Over a period of 2 weeks all patients who were treated in the department for orthopedic and trauma surgery on an outpatient basis were included in the assessment of the process. Personnel in the policlinic were prepared and trained to record times for appointments made by telephone, arrival time at the hospital, first contact, administrative procedure, first contact with the doctor, length of stay in the radiology and anesthesiology departments and completion of treatment. In addition, potential inefficiencies were identified through patient flow analysis and personal interviews with personnel in the administration and outpatient departments as well as residents and senior physicians. RESULTS: A total of 126 patients were enrolled in the study. The average length of stay of patients in the outpatient clinic was 144 min (range 30-371 min). A necessary imaging examination increased the length of stay by an average of 53 min and a necessary premedication by an average of 78 min compared to patients with no further consultations. CONCLUSION: By analyzing the pathways and times of patients, various reasons for waiting times in the university outpatient clinic could be shown. This study shows that a structured application of lean management and a dedicated analysis create added value for patients by reducing waiting times.

[Challenges of discharge management in geriatric traumatology : Example of an integrated orthogeriatric service]. / Herausforderungen des Entlassmanagements in der Alterstraumatologie : Beispiel einer integrierten traumatologisch-geriatrischen Komplexbehandlung.

BACKGROUND: Geriatric patients are currently responsible for almost one third of all emergency hospital admissions. An increase of 50% is expected in the next decade. This age redistribution poses new challenges for inpatient care and discharge management. The requirements of an orthopedic trauma surgery clinic in the care of this patient group can be clarified with the help of this first collaboratively created geriatric orthopedic trauma surgery complex treatment unit of a university hospital. OBJECTIVE: What influence do age and delirium have on discharge management, length of inpatient stay and discharge destination in a geriatric cohort? MATERIAL AND METHODS: All patients who received inpatient treatment as part of the orthopedic trauma surgery geriatric complex treatment (GKB) between May 2017 and December 2019 were evaluated. An analysis of the demographics, length of inpatient stay, discharge destinations and evaluation of the Barthel index collected on admission and discharge, the mini-mental state examination (MMSE) and the geriatric depression scale (GDS) were carried out. RESULTS: Out of 312 patients, 110 men and 193 women with a median age of 81 years, 77 patients (24.6%) showed delirium when enrolled in the GKB and 39 (12.5%) dementia. Older patients presented more often with delirium than younger people (p = 0.013), especially those aged 70-79 years (p = 0.037). Dementia patients suffered more frequently from postoperative delirium (p < 0.01). The mean hospital stay was 17.79 days (±4.6 days). The GKB was regularly completed in 60.7% of all cases and 39.3% patients dropped out early. Patients with delirium were discharged significantly less often into their own home but into short-term care or nursing homes (p = 0.038). A general correlation between delirium development and the discharge destination was noticeable (p = 0.004). CONCLUSION: Patients with dementia are more likely to develop delirium postoperatively, which leads to an increase in the length of inpatient stay, an increase in treatment costs and more work for the discharge management team. In addition, the discharge to the patients' home is impaired by delirium, which means that the growing need for places in short-term care and nursing homes also creates socioeconomic burdens.

[Process optimization in the operating room area]. / Prozessoptimierung im operativen Bereich.

BACKGROUND: The operating room (OR) accounts for the highest fraction of hospital costs and also has the largest proportion of revenue. Classical goals of optimizing OR efficiency are to increase the quality of treatment and economic success. As the reduction of qualified personnel as the largest cost factor was favored for many years, nowadays a shortage of nursing personnel is threatening the surgery departments in many German hospitals. OBJECTIVE: Which improvements are possible while the OR already suffers from restrictions? What are critical resources, what are the critical burdens and how can they be optimized? MATERIAL AND METHODS: An analysis of the OR organization of an orthopedic and traumatology department with reduced OR capacity due to a shortage of OR and anesthesia nursing personnel was performed. This was followed by the evaluation of possible alterations with the corresponding advantages and disadvantages. After selection and implementation, the qualitative and quantitative differences were examined before and after the alterations. RESULTS: Multifaceted problem areas could be identified. The establishment of a fast track OR with concentration of additional resources on many fast points in an OR instead of on a few complex cases was selected and implemented. The installation of a holding area for patients waiting for surgery eliminated transportation delays almost entirely. Alterations in the OR planning and capacity distribution reduced nocturnal operating times. Despite reduction of the OR capacity both the number of operations performed and the incision to suture times could be increased. CONCLUSION: Optimization of the processes in the OR is possible and necessary, despite the lack of personnel. Even only a few structural changes can eliminate bottlenecks, resulting in qualitative and quantitative improvements.

[Medical service providers as bottleneck in orthopedics and trauma surgery : Problems and solution strategies in interdisciplinary collaboration]. / Medizinische Dienstleister als Nadelöhr in Orthopädie und Unfallchirurgie : Probleme und Lösungsstrategien in der interdisziplinären Zusammenarbeit.

BACKGROUND: Due to limited financial and human resources, efficient planning of patient flows, operation preparations and perioperative diagnostics are of great importance. In the present study potential problems and solution strategies in the interdisciplinary collaboration between orthopedic surgeons, trauma surgeons and colleagues in anesthesiology and radiology departments are presented. MATERIAL AND METHODS: After implementation of a process management system, the data were collated and the number of patients, the utilization of external departments in the consultation, waiting times and patient adherence to appointments were analyzed. Patient satisfaction was determined using a questionnaire. In addition, the current literature was searched regarding the topic of process optimization and interdisciplinary cooperation. RESULTS: The waiting time for an appointment in the outpatient clinic consultation in orthopedics and trauma at the University Hospital Bonn was between 9.15 and 11.23 days. Of the patients 10-20% from the consultation presented in the premedication outpatient department. Radiological imaging was performed in 22-28% of the cases. Patient satisfaction was recorded using a questionnaire gathering information on medical treatment, organization and infrastructure as well as treatment success. The importance of an efficient and digitally organized cooperation is generally promoted in the literature; however, there is insufficient data on the subject of process organization and economic interdisciplinary cooperation. CONCLUSION: By implementing a process management, deficiencies in the workflow and interdisciplinary collaboration can be identified and optimized in a structured manner. This also improves patient and employee satisfaction and the quality of treatment.

Three-dimensional thoracoscopic vertebral body replacement at the thoracolumbar junction.

OBJECTIVE: The aim is to stabilize the thoracolumbar spine with a thoracoscopically implanted vertebral body replacement (VBR). To improve intraoperative depth perception and orientation, implantation is performed under three-dimensional (3D) thoracoscopic vision. INDICATIONS: Vertebral burst fractures at the thoracolumbar junction (A4 AOSpine classification), pseudarthrosis, and posttraumatic instability with increasing kyphosis. CONTRAINDICATIONS: Severe pulmonary dysfunctions, pulmonary or thoracic infections, previous thoracic surgery, and pulmonary adhesions. SURGICAL TECHNIQUE: The patient is lying in a right lateral decubitus position. Localization of the fractured vertebra. Minimally invasive transthoracic approach. Perform single lung ventilation and insert the 3D thoracoscope two intercostal spaces above the working portal. Utilization of special binocular glasses for 3D vision of the operation field and secure resection of the fractured vertebra. Measurement of the bony defect and insertion of the expandable cage. Control of correct cage position under fluoroscopy. Insertion of a chest tube and inflate the left lung. POSTOPERATIVE MANAGEMENT: Chestâ€¯× ray Remove chest tube when output is <500 ml/24 h Early mobilization on the ward 6 weeks no weight-bearing >5 kg RESULTS: Between 2012 and 2017, 12 patients received a VBR under 3D thoracoscopic vision. After a mean follow up of 26 months, no cage dislocation was noticed and all patients recovered from the initial back pain. Complications were notable in two cases (17%) with a small pneumothorax after removal of the chest tube and postoperative pneumonia in one patient (8%). All responded to conservative treatment. Revision surgery was not necessary.

Technical note: Method for isolation of the bovine sweat gland and conditions for in vitro culture.

Apocrine sweat glands in bovine skin are involved in thermoregulation. Human, horse, and sheep sweat gland epithelial cells have been isolated and grown in vitro. The present study was conducted to identify a method to isolate bovine sweat glands and culture apocrine bovine sweat gland epithelial cells in vitro. Mechanical shearing, collagenase digestion, centrifugation, and neutral red staining were used to identify and isolate the apocrine glands from skin. Bovine sweat glands in situ and after isolation comprised 2 major cell types consisting of a single layer of cuboidal epithelial cells resting on a layer of myoepithelial cells. In situ, the glands were embedded in a collagen matrix primarily comprising fibroblasts, and some of these cells were also present in the isolated material. The isolated material was transferred to complete medium (keratinocyte serum-free medium, bovine pituitary extract, and human recombinant epidermal growth factor + 2.5% fetal bovine serum) in a T 25 flask (Falcon, Franklin Lakes, NJ) with media film and then incubated at 37°C for 24 h. After sweat glands adhered to the bottom of the flask, an additional 2 mL of complete medium was added and the medium was changed every 3 d. Isolated apocrine sweat glands and bovine sweat gland epithelial cells were immunostained for cytokeratin and fibroblast specific protein, indicating fibroblast-free cultures.

TNF receptors 1 and 2 exert distinct region-specific effects on striatal and hippocampal grey matter volumes (VBM) in healthy adults.

Tumour necrosis factor alpha (TNFα) has been implicated in the pathophysiology of neurodegenerative and neuropsychiatric disease, with research highlighting a role for TNFα in hippocampal and striatal regulation. TNFα signals are primarily transduced by TNF receptors 1 and 2 (TNFR1 and TNFR2), encoded by TNFRSF1A and TNFRSF1B, which exert opposing effects on cell survival (TNFR1, neurodegenerative; TNFR2, neuroprotective). We therefore sought to explore the respective roles of TNFR1 and TNFR2 in the regulation of hippocampal and striatal morphology in an imaging genetics study. Voxel-based morphometry was used to analyse the associations between TNFRSF1A (rs4149576 and rs4149577) and TNFRSF1B (rs1061624) genotypes and grey matter structure. The final samples comprised a total of 505 subjects (mean age = 33.29, SD = 11.55 years; 285 females and 220 males) for morphometric analyses of rs1061624 and rs4149576, and 493 subjects for rs4149577 (mean age = 33.20, SD = 11.56 years; 281 females and 212 males). Analyses of TNFRSF1A single nucleotide polymorphisms (SNPs) rs4149576 and rs4149577 showed highly significant genotypic associations with striatal volume but not the hippocampus. Specifically, for rs4149576, G homozygotes were associated with reduced caudate nucleus volumes relative to A homozygotes and heterozygotes, whereas for rs4149577, reduced caudate volumes were observed in C homozygotes relative to T homozygotes and heterozygotes. Analysis of the TNFRSF1B SNP rs1061624 yielded a significant association with hippocampal but not with striatal volume, whereby G homozygotes were associated with increased volumes relative to A homozygotes and heterozygotes. Our findings indicate a role for TNFR1 in regulating striatal but not hippocampal morphology, as well as a complementary role for TNFR2 in hippocampal but not in striatal morphology.

Progesterone-induced miR-133a inhibits the proliferation of endometrial epithelial cells.

AIM: This study aimed to understand the role of miR-133a in progesterone actions, explore the regulative mechanism of the progesterone receptor, and investigate the effects of miR-133a on the progesterone-inhibited proliferation of mouse endometrial epithelial cells. METHODS: The expression of miR-133a induced by progesterone was detected by quantitative real-time PCR both in vivo and in vitro. Ishikawa subcell lines stably transfected with progesterone receptor subtypes were used to determine the receptor mechanism of progesterone inducing miR-133a. Specific miR-133a mimics or inhibitors were transfected into mouse uteri and primary cultured endometrial epithelial cells to overexpress or downregulate the miR-133a. The roles of miR-133a in the cell cycle and proliferation of endometrial epithelial cells were analysed by flow cytometry and Edu incorporation analysis. The protein levels of cyclinD2 in uterine tissue sections and primary cultured endometrial epithelial cells were determined by immunohistochemistry and Western blot analysis. RESULTS: Progesterone could induce miR-133a expression in a PRB-dependent manner in endometrial epithelial cells. miR-133a inhibited endometrial epithelial cell proliferation by arresting cell cycle at the G1 -S transition. Moreover, miR-133a acted as an inhibitor in downregulating cyclinD2 in endometrial epithelial cells. CONCLUSION: We showed for the first time that progesterone-induced miR-133a inhibited the proliferation of endometrial epithelial cells by downregulating cyclinD2. Our research indicated an important mechanism for progesterone inhibiting the proliferation of endometrial epithelial cells by inducing special miRNAs to inhibit positive regulatory proteins in the cell cycle.

[The Role of a Modular Universal Tumour and Revision System (MUTARS®) in Lower Limb Endoprosthetic Revision Surgery - Outcome Analysis of 25 Patients]. / Tumorprothesen in der endoprothetischen Revisionschirurgie der unteren Extremität ­ Ergebnisse von 25 Patienten nach Versorgung mit einem modularen Tumor- und Revisionssystem (MUTARS®).

Introduction/Background: With extended life expectancy, the number of primary joint arthroplasties has also increased. Revision surgery is also more often necessary, due to aseptic or septic loosening of the prosthesis or periprosthetic fracture. Large bone defects often occur in these patients and several non-modular, conventional implants are available to handle this difficult situation. Custom made implants offer an individually designed and defect-adapted shape with perfect covering of the lesion, but may delay the operation. The Modular Universal Tumor And Revision System (MUTARS®) offers the possibility to vary the length and angle of the femoral neck and the antetorsion angle. Thus, it permits intraoperative adaption to the individual patient's defect. The aim of our study is to present clinical, functional results and the rate of complications in a cohort of patients undergoing revision surgery for failed endoprosthetic replacement or failed trauma surgery, using the Modular Universal Tumor And Revision System with short-to midterm follow-up. Patients and Methods: Between August 2005 and September 2014, 25 patients (17 female, 8 male) with an average age of 72 years (min. 56, max. 92 years) were included in a retrospective study using the MUTARS® system. The patients underwent surgical revision of osseous defects that were not susceptible to conventional care. The mean follow-up was 16 months (min. 12, max. 72 months). The indications which led to revision surgery were as follows: loosened metal-on-metal prosthesis with an acetabular defect caused by a metal-induced granuloma (n = 1), pseudoarthrosis after implantation of femur nail (n = 2), cut-out of a femur nail (n = 1), aseptic loosening of an implanted endoprosthesis (n = 4), septic loosening of an implanted endoprosthesis (n = 1), periprosthetic fracture (n = 6) and periprosthetic infection after two stage revision surgery (infection consolidated Girdlestone situation) (n = 10). All patients were followed up at regular intervals, both clinically and radiologically. Apart from comorbidities, clinical and functional parameters were measured, including the Harris Hip Score. An outcome analysis was also performed with respect to peri- and postoperative complications. Serial plain X-rays were followed-up. Results: In all patients, stable reconstruction without the use of an allograft was possible. In total, 23 patients underwent surgery by using a proximal femur prosthesis; three patients also received a custom made acetabular component. One patient was treated by using a distal femur and one patient was treated by implantation of a total femur prosthesis. The average length of hospital stay was 25 days (min.11, max. 47 days). The Harris Hip Score improved from 28 points preoperatively to 81 points after surgery.In total we recorded 24 % of complications after surgery. Two patients suffered recurrent periprosthetic infection and the prosthesis had to be revised in a further two stage exchange; one patient had a tractus gap and was revised by surgery. Two patients suffered periprosthetic fracture due to trauma and the patient with the total femur prosthesis suffered recurrent periprosthetic infection of the silver - coated mega-prosthesis and committed suicide triggered by an episode of major depression. Conclusion: Because of its modular nature, the Modular Tumor And Revision System (MUTARS®) can be used for highly variable intraoperative defect adaption. Good clinical and functional results were achieved in patients with excessive bone defects. However, the high rate of infection, even with silver coated mega-implants, is still a problem and should be studied further.

Nomogram for 30-day morbidity after primary cytoreductive surgery for advanced stage ovarian cancer.

PURPOSE OF INVESTIGATION: Extensive surgical procedures to achieve maximal cytoreduction in patients with advanced stage epithelial ovarian cancer (EOC) are inevitably associated with postoperative morbidity and mortality. This study aimed to identify preoperative predictors of 30-day morbidity after primary cytoreductive surgery for advanced stage EOC and to develop a nomogram for individual risk assessment. MATERIALS AND METHODS: Patients in The Netherlands who underwent primary cytoreductive surgery for advanced stage EOC between January 2004 and December 2007. All peri- and postoperative complications within 30 days after surgery were registered and classified. To investigate predictors of 30-day morbidity, a Cox proportional hazard model with backward stepwise elimination was utilized. The identified predictors were entered into a nomogram. The main outcome was to identify parameters that predict operative risk. RESULTS: 293 patients entered the study protocol. Optimal cytoreduction was achieved in 136 (46%) patients. Thirty-day morbidity was seen in 99 (34%) patients. Morbidity could be predicted by age (p = 0.033; OR 1.024), preoperative hemoglobin (p = 0.194; OR 0.843), and WHO performance status (p = 0.015; OR 1.821) with a optimism-corrected c-statistic of 0.62. Determinants co-morbidity status, serum CA125 level, platelet count, and presence of ascites were comparable in both groups. CONCLUSIONS: Thirty-day morbidity after primary cytoreductive surgery for advanced stage EOC could be predicted by age, hemoglobin, and WHO performance status. The generated nomogram could be valuable for predicting operative risk in the individual patient.

Perioperative management and outcome of fracture treatment in patients with haemophilia without inhibitors.

INTRODUCTION: Fractures in persons with haemophilia (PWH) are not uncommon and require an interdisciplinary approach to maintain haemostasis during surgical treatment. AIM: The aim of this study was to evaluate the perioperative management and outcome in PWH following fracture fixation compared to a matched non-haemophilic control group. METHODS: A cohort of 44 PWH who underwent 46 surgical fracture fixations was retrospectively compared to 46 non-haemophilic patients (matched-pair controls). Patients were classified according to the fracture localization: (i) proximal upper extremity (PrUEx; n = 7), (ii) distal upper extremity (DiUEx; n = 12), (iii) proximal lower extremity (PrLEx; n = 13) and (iv) distal lower extremity (DiLEx; n = 14). Both groups were assessed for length of hospital stay, duration of surgery, drainage use and complication rates. RESULTS: There was no significant difference regarding the duration of the preoperative hospital stay between PWH and controls. Only PWH who were operated at the DiUEx stayed significantly longer in hospital (4.8 ± 3.7 days) than controls (2.2 ± 2.3 days; P = 0.039). Operation time was significantly longer in PWH with fractures treated at the DiLEx (64.9 ± 26.6 min) compared to the controls (49.8 ± 37.9 min; P = 0.035). Neither frequency nor duration of surgical drainage placement differed significantly between the two groups. The overall complication rate in both groups was low without a statistically significant difference. CONCLUSION: An optimal interdisciplinary perioperative management provided the surgical treatment of fractures in PWH can be performed safely with a low complication rate.

[The "Muffplastik"--a Fasciocutaneous Reconstruction Technique in a Case of Extensive Soft Tissue Defect of the Distal Forearm--Historical Technique or Salvage Procedure?]. / Die "Muffplastik": fasziokutane Bauchhautlappenplastik zur Deckung eines ausgeprägten Defekts an der Hand und am distalen Unterarm--historischer Eingriff oder Rückzugsoption?

We present a case of a distant pedicled flap to reconstruct a defect at the distal upper extremity. We used this flap as a salvage procedure to treat a patient in the intensive care unit who was in a reduced general condition with numerous comorbidities that made regional or free microvascular flaps hazardous.

[Surgical treatment of sternoclavicular joint instability with tenodesis]. / Die operative Therapie der sternoklavikulären Instabilität mittels Tenodese.

BACKGROUND: Instability of the sternoclavicular joint is a very uncommon disorder of the shoulder girdle. Acute traumatic dislocations are commonly treated nonoperatively. But severe displacement or chronic instability with recurrent symptomatic subluxation may require surgical intervention. We present our results with open reduction and internal fixation through an autologous gracilis tendon transplant or fiber tape in 8 patients treated surgically. The operative stabilisation of the sternoclavicular joint reduces pain level and improves function of the shoulder. This technique provides an effective surgical procedure for treatment of symptomatic sternoclavicular joint instability. OBJECTIVE: Restoration of the function and aspect of the sternoclavicular joint. INDICATIONS: Chronic and painful instabilities. CONTRAINDICATIONS: Local infection, tumor. SURGICAL TECHNIQUE: The gracilis tendon graft is harvested as previously described by Petersen. Direct incision over the sternoclavicular joint. Sharp dissection of the periostal sleeve and partial release of sternocleidomastoideus and pextoralis muscle. Resection of osteophytes. Careful placement of a raspatorium under the proximal clavicle and sternum to protect the mediastinal structures. Application of 2.5 or 3.2 mm drill holes to the sternum and the proximal clavicle. The gracilis tendon or the fiber tape is pulled through the drill holes in a figure of eight and then sutured. Recontruction of the joint capsule, closure of the wound. POSTOPERATIVE MANAGEMENT: Gilchrist brace for 3-5 days, functional physiotherapy with a maximum abduction of 90° for 6 weeks. No carrying or lifting of weights greater than 5 kg for 3 months. RESULTS: During the period from January 2006 to December 2010, 8 patients with sternoclavicular instability were treated. Four patients were treated with fiber tape and four were treated with a gracilis tendon autograft. Postoperative all patients described a reduction of pain and improved shoulder function. The Constant score was 72 points, the DASH 58 points.

Melanoma risk after ovarian stimulation for in vitro fertilization.

STUDY QUESTION: Do women treated with ovarian stimulation for IVF have an increased risk of melanoma? SUMMARY ANSWER: Ovarian stimulation for IVF does not increase risk of melanoma, even after a prolonged follow-up. WHAT IS KNOWN ALREADY: Although exposure to ultraviolet radiation is the major risk factor for melanoma, associations between female sex steroids and melanoma risk have also been suggested. The results of available studies on fertility drugs and melanoma risk are inconclusive since most studies had several methodological limitations such as short follow-up, a small number of cases and no subfertile comparison group. STUDY DESIGN, SIZE, DURATION: In 1996, a nationwide historic cohort study (the OMEGA-cohort) was established to examine the risk of cancer after ovarian stimulation for IVF. After a median follow-up of 17 years, cancer incidence was ascertained through linkage with the Netherlands Cancer Registry. Melanoma risk in the cohort was compared with that in the general population and between the IVF group and non-IVF group using multivariable Cox regression analyses. PARTICIPANTS/MATERIALS, SETTING, METHODS: The cohort comprises 19 158 women who received IVF between 1983 and 1995 and a comparison group of 5950 women who underwent subfertility treatments other than IVF. Detailed IVF-treatment data were obtained from the medical records and complete information on parity and age at first birth was obtained through linkage with the Dutch Municipal Personal Records Database. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 93 melanoma cases were observed. The risk of melanoma was not elevated among IVF-treated women, neither when compared with the general population (standardized incidence ratio = 0.89; 95% confidence interval (CI): 0.69-1.12), nor when compared with the non-IVF group (adjusted hazard ratio (HR) = 1.27; 95% CI: 0.75-2.15). A higher number of IVF cycles was associated with apparent but statistically non-significant risk increases (5-6 cycles HR = 1.92; ≥7 cycles HR = 1.79). However, no significant trend emerged. In women with more follicle stimulating hormone/human menopausal gonadotrophin ampoules comparable non-significant risk increases were found. A longer follow-up did not increase melanoma risk. Nulliparous women did not have a significantly higher melanoma risk than parous women (HR = 1.22; 95% CI: 0.81-1.84). However, women who were 30 years of age or older at first birth had a significantly higher melanoma risk than women who were younger than 30 years at first birth (age: 30-34 years HR = 4.57; 95% CI: 2.07-10.08, >34 years HR = 2.98; 95% CI: 1.23-7.21). LIMITATIONS, REASONS FOR CAUTION: Despite our large cohort, the number of melanoma cases was rather small, especially in our comparison group, which hampered subgroup analyses. WIDER IMPLICATIONS OF THE FINDINGS: Our results are reassuring for women who underwent IVF or are contemplating to start IVF. Since our cohort study is one of the largest published so far, with long-term follow-up, a subfertile comparison group, and detailed IVF-treatment data, our results add important information to the available evidence. STUDY FUNDING/COMPETING INTEREST: This study was supported by grants from the Dutch Cancer Society (NKI 2006-3631), the Health Research and Development Counsel (28-2540) and the Dutch Ministry of Health.

Increased breast cancer risk in in vitro fertilisation treated women with a multiple pregnancy: a new hypothesis based on historical in vitro fertilisation treatment data.

BACKGROUND: Breast cancer risk is temporarily increased after a full-term pregnancy and declines thereafter, possibly due to increased levels of gonadal and placental hormones during pregnancy. Inconsistent results, however, have been reported after twin pregnancies with higher hormone levels. Among women treated with in vitro fertilisation (IVF), for whom the number of embryos available for implantation is known, we recently observed that a multiple birth after implantation of all transferred embryos is associated with higher levels of vascular endothelial growth factor (VEGF). As VEGF is involved in breast cancer progression, we studied the effects of embryo implantation and a multiple birth on breast cancer risk in a nationwide Dutch cohort of IVF-treated women. METHODS: We performed a cohort analysis among 12,589 women who had been treated with IVF between 1983 and 1995 and completed a risk factor questionnaire between 1997 and 1999. Data on IVF treatment were obtained from medical records. Breast cancer cases were ascertained through linkage with the population-based Netherlands Cancer Registry. Breast cancer risks associated with singleton and multiple births were estimated with Cox regression. FINDINGS: There were 1688 women (13.4%) with multiples, 6027 (47.9%) with singletons and 4874 (38.7%) nulliparous women. Breast cancer occurred in 317 women of whom 57 had multiples. Breast cancer risk was 1.44 times higher in mothers of multiples than in mothers of singletons (95% confidence interval (CI) 1.06-1.97). Risk was highest in women who gave birth to multiples from all embryos transferred (adjusted hazard ratio (HR) 1.86, 95% CI 1.01-3.43), and lower for those with multiples after incomplete embryo implantation (adjusted HR 1.31, 95% CI 0.76-2.25). INTERPRETATION: A woman's potential to implant all transferred embryos may be associated with breast cancer risk. Further research is needed to confirm our results and to identify the underlying biological mechanisms.

Real-time dosimetry reduces radiation exposure of orthopaedic surgeons.

BACKGROUND: Cancer prevalence of orthopaedic surgeons is elevated and chronic exposure to occupational ionizing radiation is seen as one reason. HYPOTHESIS: Use of a new dosimeter enabling radiation dose monitoring in real-time may reduce radiation exposure of orthopaedic surgeons. MATERIALS AND METHODS: Over a period of four months, the surgeon and the C-arm operator were equipped with a novel dosimeter called DoseAware(®) (DA) while using the C-arm fluoroscope intraoperatively. Data of 68 patients DA were retrospectively compared using matched-pair analysis with 68 controls without DA. Both groups were assessed regarding fluoroscopic time (FT) and radiation dose (RD). Seven types of operative procedures were performed: internal fixation of subcapital humerus fractures, midshaft clavicular fractures, distal radius fractures, pertrochanteric femoral fractures, ankle fractures, traumatic vertebral fractures and osteoporotic vertebral fractures. RESULTS: Concerning the FT, use of DoseAware(®) led to a significant reduction for all evaluated operation types except for internal fixation of distal radius fractures (P=0.0511). Regarding the RD, use of DoseAware(®) led to a significant reduction for all evaluated operation types except trochanteric femoral fractures with a PFNA(®) (P=0.0841). CONCLUSION: DoseAware(®) allowing real-time radiation dose monitoring reduces radiation exposure of the orthopaedic surgeon and instantly demonstrates the effects of dose-reduction techniques. LEVEL OF EVIDENCE: Level III retrospective case control study.

[Evaluation of radiation exposure of personnel in an orthopaedic and trauma operation theatre using the new real-time dosimetry system "dose aware"]. / Evaluation der Strahlenexposition des Operationspersonals bei orthopädisch-unfallchirurgischen Operationen mithilfe des neuen Echtzeitdosimetriesystems "Dose Aware"

AIM: There is a positive correlation between operation time and staff exposure to radiation during intraoperative use of C-arm fluoroscopy. Due to harmful effects of exposure to long-term low-dose radiation for both the patient and the operating team it should be kept to a minimum. AIM of this study was to evaluate a novel dosimeter system called Dose Aware® (DA) enabling radiation exposure feedback of the personal in an orthopaedic and trauma operation theatre in real-time. METHOD: Within a prospective study over a period of four month, DA was applied by the operation team during 104 orthopaedic and trauma operations in which the C-arm fluoroscope was used in 2D-mode. During ten operation techniques, radiation exposure of the surgeon, the first assistant, the theatre nurse and the anaesthesiologist was evaluated. RESULTS: Seventy-three operations were analysed. The surgeon achieved the highest radiation exposure during dorsolumbar spinal osteosynthesis, kyphoplasty and screw fixation of sacral fractures. The first assistant received a higher radiation exposure compared to the surgeon during plate osteosynthesis of distal radius fractures (157 %), intramedullary nailing of pertrochanteric fractures (143 %) and dorsolumbar spinal osteosynthesis (240 %). During external fixation of ankle fractures (68 %) and screw fixation of sacral fractures (66 %) radiation exposure of the theatre nurse exceeded 50 % of the surgeon's radiation exposure. During plate osteosynthesis of distal radius fractures (157 %) and intramedullary splinting of clavicular fractures (115 %), the anaesthesiologist received a higher radiation exposure than the surgeon. CONCLUSION: The novel dosimeter system DA provides real-time radiation exposure feedback of the personnel in an orthopaedic and trauma operation theatre for the first time. Data of this study demonstrate that radiation exposure of the personnel depends on the operation type. The first assistant, the theatre nurse and the anaesthesiologist might be exposed to higher radiation doses than the surgeon. DA might help to increase awareness concerning irradiation in an orthopaedic and trauma operation theatre and might enhance staff compliance in using radiation protection techniques.

Progesterone-induced cyclin G1 inhibits the proliferation of endometrial epithelial cell and its possible molecular mechanism.

Under normal conditions, progesterone inhi-bits the estrogen-induced proliferation of endometrial epithelium. Our previous studies have shown that cyclin G1 was progesterone-dependent in mouse endometrial epithelium at peri-implantation, and exogenous cyclin G1 suppressed the proliferation of endometrial cancer cells. The objectives of this study are to determine whether cyclin G1, as a negative regulator of the cell cycle, is involved in the antiproliferative action of progesterone on endometrial epithelial cells, and to explore the possible molecular mechanism of cyclin G1 inhibition. The siRNA-mediated elimination of cyclin G1 attenuated the antiproliferative action of progesterone on endometrial epithelial cells. Immunoprecipitation showed that progesterone-induced cyclin G1 could interact with PP2A to mediate its phosphatase activity. The block of PP2A activity also attenuated the antiproliferative action of progesterone on endometrial epithelial cells and increased the phosphorylated Rb. In conclusion, progesterone-induced cyclin G1 mediates the inhibitory effect of progesterone on endometrial epithelial cell proliferation possibly through the recruitment of PP2A to dephosphorylate Rb.

PMMA-augmentation of incompletely cannulated pedicle screws: a cadaver study to determine the benefits in the osteoporotic spine.

BACKGROUND: Pedicle screw pullout due to poor bone quality, mainly caused by osteoporosis, is a common problem in spine surgery. Special implants and techniques, especially PMMA augmentation, were developed to improve the fixation of pedicle screws. PMMA injection into a pilot hole or through a screw involves the same risks as vertebroplasty or kyphoplasty, regardless of the technique used. Especially when using fully cannulated screws anterior leakage is possible. OBJECTIVE: To prove PMMA injection is safe and possible without leakage through an incompletely cannulated screw and also increases pullout forces in the osteoporotic vertebra. METHODS: Incompletely cannulated pedicle screws were tested by axial pullout in human cadavers, divided into osteoporotic and non-osteoporotic groups. Non-augmented and PMMA-augmented pedicle screws were compared. Twenty-five human vertebrae were measured by DEXA and divided into osteoporotic and non-osteoporotic groups. In each vertebra both pedicles were instrumented with the new screw (WSI-Expertise 6×45 mm, Peter Brehm Inc. Germany); the right screw was augmented with a 3 mL PMMA injection through the screw. On each screw axial pullout was performed after X-ray and CT scan. RESULTS: Radiographs and CT scans excluded PMMA leakage. Cement was distributed in the middle and posterior third of the vertebrae. Pullout forces were significantly higher after pedicle screw augmentation, especially in the osteoporotic bone. All augmented pedicle screws showed higher pullout forces compared with the unaugmented screws. CONCLUSIONS: We minimized the risk of leakage by using a screw with a closed tip. On the whole, PMMA augmentation through an incompletely cannulated pedicle screw is safe and increases pullout forces in osteoporotic bone to the level of healthy bone. Therefore the new incompletely cannulated screw can be used for pedicle screw augmentation.