Exogenous Estrogen in the Development of Head and Neck Cancer.

Importance: Sex differences in head and neck cancer (HNC) incidence suggest a potential contribution of sex hormones. Objective: To assess the role of exogenous estrogen exposure in the development of HNC in female patients. Design, Settings, and Participants: This large multicenter cohort study using clinical records from the TriNetX real-world database included 20 years of data (through May 31, 2023) from 87 health care organizations. The TriNetX database was searched for medical records for female patients with and without exogenous estrogen exposure according to their chronological age. Cohort 1 included 731 366 female patients aged 18 to 45 years old with regular oral contraceptive (OC) intake and cohort 2 included 3 886 568 patients in the same age group who did not use OC. Cohort 3 comprised 135 875 female patients at least 50 years old receiving hormone replacement therapy (HRT), whereas cohort 4 included 5 875 270 patients at least 50 years old without HRT. Propensity score matching was performed for the confounders age, alcohol dependence, and nicotine dependence. Data analyses were performed in May 2023. Main Outcome and Measures: Diagnosis of HNC (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision: C00-C14), and after propensity score matching (1:1 nearest-neighbor greedy matching), a risk analysis to investigate risk differences and risk ratios (RRs) with a 95% CI. Results: Among the 718 101 female patients in each of cohorts 1 and 2 (mean [SD] age at diagnosis, 25.9 [6.7] years), those with OC intake had a higher risk of an HNC diagnosis (RR, 1.47; 95% CI, 1.21-1.78) than those without OC use. Among the 131 835 female patients in each of cohorts 3 and 4 (mean [SD] age, 67.9 [12.0] years), those with postmenopausal HRT intake had a lower risk of an HNC diagnosis (RR, 0.77; 95% CI, 0.64-0.92) than those without HRT use. Conclusions and Relevance: The findings of this cohort study illustrate a positive association between OC and a negative association between HRT and the development of HNC in female patients. Given the limitations of the TriNetX database, future research should include detailed information on the intake of OC and HRT and reproductive health information (eg, age at menarche/menopause, number of pregnancies) to more accurately define the strength and direction of the possible association between exogeneous estrogen exposure and the development of HNC in female patients.

A modified pull-through approach with a pedicled bone flap for oral and oropharyngeal cancer resection: a feasibility study.

PURPOSE: Compromised swallowing, speaking, and local complications are the major disadvantages of established approaches to the posterior tongue and oropharynx. The mandibular split involves an esthetically unpleasant bipartition of the lower lip and is prone to bony non-union or sequestration. The conventional pull-through technique on the other hand lacks the secure reattachment of the lingually released soft tissues. METHODS: The feasibility of a new modified pull-through approach was tested on three anatomical specimens. CAD/CAM cutting guides were used to design a retentive bone flap to properly refixate the genioglossus and geniohyoid muscles after the procedure. The radiographic assessment and treatment planning was performed on 12 cadavers. The entire procedure was tested surgically via dissection in three of those cases. This procedure was then applied in a clinical case. RESULTS: Precise repositioning and dynamic compression of bony segments was possible reproducibly and without injury to adjacent structures. In all dissected cases, a median lingual foramen was found and in two cases vessels entering it could be dissected Radiologic anatomical landmarks were sufficient in all 12 cases to perform the clinical planning procedure. Clinically, the osteotomized segment demonstrated good blood supply and plateless repositioning was verified postoperatively via cone beam scan. CONCLUSION: The method presented is safe and easy to perform. Individual cutting guides improve the safety and accuracy of the procedure, potentially eliminating the need for osteosynthesis. We provide the anatomical and radiologic basis for clinical evaluation of this pedicled bone flap procedure and present the clinical application of this modified pull-through approach.

Diagnostic pitfalls in pediatric orbital entrapment fractures.

Prompt diagnosis and management of orbital entrapment fractures in the pediatric patient have been advocated. This retrospective study analyzed a cohort of orbital entrapment fractures in pediatric patients with regard to diagnostic pitfalls, treatment and outcomes in a Level I trauma center in Germany. Based on medical records and radiological imaging, patients under the age of 18 years who presented with orbital fractures during 2009-2021 were analyzed. Overall, 125 patients presented with orbital fractures, of whom 29 patients (23.2%) had orbital entrapment fractures. The majority of patients presented with monocle hematoma (n = 23), diplopia (n = 20), and/or restricted extraocular eye movement (n = 14). While all patients with orbital entrapment fractures underwent three-dimensional imaging, 10 radiological reports (34.5%) did not include findings on orbital entrapment fractures. All patients underwent surgical exploration in less than 24 h. In 12 patients, clinical symptoms such as diplopia and restricted ocular elevation were documented upon postoperative evaluation before discharge. Considering the significant proportion of orbital entrapment fractures that are not noted on radiological imaging, prompt clinical examination should be initiated in pediatric patients at risk for orbital fractures. Urgent surgical intervention should be recommended in entrapment fractures.

Worse prognosis in females with new onset of depression after oral cancer diagnosis: a retrospective case-control study.

Background: Sex-related discrepancies in the prognosis of oral cancer patients have not been clarified. This study aimed to assess survival outcomes and potential prognostic factors in female and male patients with oral cancer. Methods: A retrospective search of the TriNetX network (TriNetX, Cambridge, Massachusetts, USA) was conducted to identify patients diagnosed with oral cancer (International Classification of Diseases (ICD)-10 codes C02-C06), within the past 20 years from the access date April 21, 2023. Patients were categorized according to sex (female vs. male). Following matching for age and risk factors such as nicotine dependence and alcohol abuse, Kaplan-Meier analysis was performed and risk, odds, and hazard ratios were calculated. Outcome variables were five-year disease-free survival (DFS) and overall survival (OS). Additionally, the female and male patient cohort were compared with regard to the novel diagnosis of depression (depressive episode, major depressive disorder, dysthymic disorder) after the tumor diagnosis. Results: A total of 77,348 patients were assessed. After propensity score matching, 26,578 male and 26,578 female patients were included in each group (mean age 63 years). DFS (71.92% in females vs. 68.29% in males; hazard ratio (HR) 0.870; p < 0.001) and OS (77.08% in females vs. 71.74% in males; HR 0.793; p < 0.001) were significantly higher in the female cohort. However, in patients diagnosed with depression after the initial cancer diagnosis (N = 4,824), survival was worse in female patients compared to male patients (82.48% in females vs. 86.10% in males; HR 1.341; p < 0.001). Conclusion: This retrospective case-control study showed that females with oral cancer had a better DFS and OS than males. However, survival in females with a newly diagnosed depression after the oral cancer diagnosis was worse compared to those of male oral cancer patients. Depression may be a relevant prognostic factor that contributes to sex disparities in oral cancer patients.

Oncologic Outcome in Advanced Oral Squamous Cell Carcinoma After Refusal of Recommended Adjuvant Therapy.

Importance: Clinicians may be confronted with patients refusing recommended adjuvant therapy (AT) after the primary resection of an advanced oral squamous cell carcinoma (OSCC). However, for this tumor entity, data are lacking regarding the oncological outcomes and associated factors after refusal of AT. Objective: To evaluate the difference in survival and disease recurrence for patients with and without recommended AT after resection of advanced OSCC. Design, Setting, and Participants: In this single-center retrospective matched cohort study, patients with advanced OSCC who refused recommended AT between January 2010 and December 2021 were matched 1:1 according to Union for International Cancer Control tumor staging with patients who completed AT. Exposures: Patients with advanced OSCC who refused or completed recommended AT between 2010 and 2021. Main Outcomes and Measures: The primary outcome of this study was the comparison of overall survival (OS) and recurrence-free survival (RFS) between the 2 study groups. Results: A total of 82 patients (mean [SD] age at time of surgery, 68.0 [11.3] years; 38 [46.3%] female, 44 [53.7%] male) with and without AT (41 per study group) were included in the analysis. Patients refusing AT developed more frequent disease recurrence than patients who completed AT (61.0% vs 26.8%; difference, 34.2%; odds ratio, 4.26; 95% CI, 1.68-10.84). In addition, patients who refused AT presented with lower 2-year OS (72.7% vs 88.6%; difference, 15.9%; 95% CI, 8.6%-40.6%) and much lower 2-year RFS (39.1% vs 74.2%; difference, 35.1%; 95% CI, 0.2%-70.5%). In the patient cohort who rejected AT, a worse OS was associated with female sex (48.6% vs 90.5%; difference, 41.9%; 95% CI, 0.6%-84.4%), pT1-2 category (57.1% vs 92.3%; difference, 35.2%; 95% CI, 3.3%-73.6%), and pN1 or higher category (61.2% vs 82.6%; difference, 21.4%; 95% CI, 14.1%-56.8%). Lower RFS was associated with female sex (37.9% vs 90.9%; difference, 53.0%; 95% CI, 8.0%-97.9%), advanced T category (pT3-4, 35.3% vs 80.0%; difference, 44.7%; 95% CI, 6.4%-95.3%), lymph node yield of 20 or greater (31.4% vs 80.6%; difference, 49.2%; 95% CI, 4.9%-93.4%), and lymph node ratio of less than 4.6% (36.6% vs 84.4%; difference, 47.8%; 95% CI, 1.8%-93.1%). Conclusions and Relevance: In this cohort study of patients with advanced OSCC, refusal of AT was associated with worse oncological outcomes. The prevalence of disease recurrence during follow-up was 34% higher in patients who refused AT than in patients who completed AT. The results from this study may assist clinicians in guiding patients who are considering refusal of or withdrawal from AT.

Sentinel lymph node biopsy in recurrent or secondary oral squamous cell carcinoma after previous neck dissection.

OBJECTIVES: The aim of this retrospective study was to evaluate the potential of sentinel lymph node biopsy (SLNB) in patients with recurrent or a secondary oral squamous cell carcinoma (OSCC) without clinical signs of lymph node metastases (cN0), who were previously treated with a surgical approach. PATIENTS AND METHODS: Retrospective analysis of all patients with cN0 recurrent or secondary OSCC, who were treated using SLNB after previous neck dissection. Endpoints were sentinel lymph node (SLN) detection rate, negative predictive value (NPV) and sensitivity. RESULTS: A total of 17 patients with a mean age of 68.6 years were included. SLN were detected in 15 of 17 cases (detection rate: 88.2%). In seven patients (41.2%), a bilateral or contralateral lymph drainage of a unilateral carcinoma was found. Two patients (11.8%) demonstrated a positive SLN upon pathohistological analysis, which led to an upstaging. In one case, a non-SLN was positive, which is considered a false-negative result. The mean follow-up for all patients with histologically negative SLN including the patients without a detected SLN was 11.8 months (range: 0-31 months). Of these, one patient developed (isolated) neck recurrence after 12 months resulting in an overall NPV of 86.7% and a sensitivity of 50.0% for the SLNB as a neck staging procedure. CONCLUSION: SLNB can improve the staging of patients with recurrent or secondary OSCC, who present with a history of a previous neck dissection. Further studies are required to demonstrate the oncological benefit of SLNB in this patient cohort.

Pediatric Maxillofacial Trauma: Insights into Diagnosis and Treatment of Mandibular Fractures in Pediatric Patients.

Aim: To assess the diagnostic and therapeutic approaches in pediatric mandibular fractures with regards to fracture pattern and localization. Patients and methods: This retrospective study included patients under the age of 17 years that presented to the Department of Oral and Maxillofacial Surgery at Charité-Universitätsmedizin Berlin with mandibular fractures over an 11-year long period (2010-2020). Medical records were analyzed for age, gender, injury mechanism, clinical presentation, imaging modalities, fracture pattern, and fracture management. Statistical analyses included descriptive statistics, normality testing, and Mann-Whitney U tests. Results: A total of 91 pediatric patients (23 females and 68 males) presented with mandibular fractures. The majority of mandibular fractures occurred in patients aged 13-16 years (67.0%, n = 61). The main causes were activities of daily life (34.1%), followed by assault (25.3%). Malocclusion and pain upon mandibular joint compression were documented in 72.5% and 51.7% of patients, respectively. The most frequently applied radiological diagnostic tool was a panoramic X-ray (49.5%). The main fracture patterns were single (42.9%) and double fractures (48.4%). An age-adapted surgical approach using open reduction and internal fixation (ORIF) was the most frequent management (61.5%). A conservative approach was favored in cases of condylar head fractures. Resorbable plates were used in eight cases of ORIF (8.8%). Conclusion: Treatment regimens should be carefully selected based on the unique anatomy of the pediatric patient with regards to centers of growth and dentition phase, to restore stomatognathic function and to maintain adequate skeletal growth and eruption of teeth. Clinical significance: This study illustrates the challenges of mandibular fracture management in the pediatric patient. How to cite this article: Hofmann E, Koerdt S, Heiland M, et al. Pediatric Maxillofacial Trauma: Insights into Diagnosis and Treatment of Mandibular Fractures in Pediatric Patients. Int J Clin Pediatr Dent 2023;16(3):499-509.

Prognostic factors in surgically treated malignant salivary gland tumors.

OBJECTIVES: To identify prognostic factors for evidence-based risk stratification in malignant salivary gland tumors. METHODS: This retrospective study identified 162 patients who presented with malignant salivary gland tumors between 2010 and 2020. Final analysis included 91 patients who underwent surgical treatment at our institution and were followed-up for ≥ 1 year. Medical records were reviewed and patients were categorized according to their risk profile. RESULTS: This study included 91 patients (51 males, 40 females, mean age 61 years). The most frequent entities were adenoid cystic carcinoma (n = 13, 14.3%) and mucoepidermoid carcinoma (n = 12, 13.2%). Kaplan-Meier analysis demonstrated a five-year overall survival (OS) of 66.2% and a recurrence-free survival (RFS) of 50.5%. Age > 60 years (p = 0.011), categorization into high-risk group (p = 0.011), UICC stage (p = 0.020), T stage (p = 0.032), grading (p = 0.045) and vascular invasion (p < 0.001) were significantly associated with OS; age > 60 years (p = 0.014), categorization into high-risk group (p < 0.001), UICC stage (p = 0.021), T stage (p = 0.017), grading (p = 0.011), vascular invasion (p = 0.012) and lymphovascular invasion (p < 0.001) were significantly associated with RFS. Multivariate Cox regression with backward elimination identified T stage (HR 1.835; 95% CI 1.187-2.836; p = 0.006) and grading (HR 2.233; 95% CI 1.113-4.480; p = 0.024) as significant factors for OS. Grading (HR 2.499; 95% CI 1.344-4.648; p = 0.004) was confirmed as a significant factor for RFS. CONCLUSION: Considering the risk of recurrence and distant metastasis in malignant salivary gland tumors, locoregional surgical control may not be sufficient and adjuvant therapies such as radiotherapy and/or systemic therapies should be considered.

A retrospective case-control study for the comparison of 5-year survival rates: the role of adjuvant and neoadjuvant chemotherapy in craniofacial bone sarcoma in adults.

Background: The impact of adjuvant or neoadjuvant chemotherapy in the treatment of craniofacial bone sarcomas has not been clarified. This study aimed to assess whether survival outcomes differed between patients who underwent adjuvant or neoadjuvant chemotherapy. Methods: A retrospective search for adult patients diagnosed with malignant neoplasms of the craniofacial bones (International Classification of Diseases 10 codes C41.0-C41.1), within the past 20 years from the access date 28 April 2022, was conducted using the TriNetX network (TriNetX, Cambridge, MA, USA). Cohort I included patients who underwent adjuvant chemotherapy and cohort II included patients with neoadjuvant chemotherapy. A refined search for individuals that received common chemotherapeutic agents, such as methotrexate, doxorubicin, cisplatin, and/or ifosfamide, was conducted and patients were assigned to cohort A (adjuvant chemotherapy) and cohort B (neoadjuvant chemotherapy). Following matching for age and sex, Kaplan-Meier analysis was performed, and risk ratio, odds ratio (OR), and hazard ratio were calculated. Results: Patients were assigned to two cohorts, with 181 patients each after matching. In cohorts I and II, 55 and 41 patients died, respectively. No significant differences were found between the two cohorts regarding the 5-year survival probability (I: 59.87% versus II: 68.45%; p = 0.076; log-rank test), or the risk of dying (I: 0.304 versus II: 0.227; risk difference: 0.077; p = 0.096). The risk analysis before matching for age and sex showed a significant survival benefit in cohort II (OR: 1.586; p = 0.0295; risk difference: 0.093). After a refined query to identify patients treated with methotrexate, doxorubicin, cisplatin, and/or ifosfamide, the two cohorts included 47 patients, respectively. In cohort A (adjuvant chemotherapy), 19 patients died, whereas 12 patients died in cohort B (neoadjuvant chemotherapy) within 5 years after diagnosis. Further analysis indicated a greater survival in cohort B, but the survival probability between the cohorts did not differ significantly (A: 43.55% versus B: 54.49%; p = 0.171). Conclusion: The use of neoadjuvant chemotherapy may improve survival rates in patients with surgically treated craniofacial bone sarcomas. Due to the retrospective nature of this study, randomized controlled studies are required to derive treatment recommendations.

Bevacizumab and sunitinib mediate osteogenic and pro-inflammatory molecular changes in primary human alveolar osteoblasts in vitro.

Antiangiogenic medications target the de novo blood vessel formation in tumorigenesis. However, these novel drugs have been linked to the onset of medication-related osteonecrosis of the jaw (MRONJ). The aim of this in vitro study was to examine the effects of the vascular endothelial growth factor A (VEGFA) antibody bevacizumab (BEV) and the receptor tyrosine kinase inhibitor (RTKI) sunitinib (SUN) on primary human osteoblasts derived from the alveolar bone. Primary human alveolar osteoblasts (HAOBs) were treated with BEV or SUN for 48 h. Cellular metabolic activity was examined by XTT assay. Differentially regulated genes were identified by screening of 22 selected osteogenic and angiogenic markers by quantitative real-time reverse transcriptase polymerase chain reaction (qRT2-PCR). Protein levels of alkaline phosphatase (ALP), collagen type 1, α1 (COL1A1) and secreted protein acidic and cysteine rich (SPARC) were examined by enzyme-linked immunoassay (ELISA). Treatment with BEV and SUN did not exhibit direct cytotoxic effects in HAOBs as confirmed by XTT assay. Of the 22 genes examined by qRT2-PCR, four genes were significantly regulated after BEV treatment and eight genes in the SUN group as compared to the control group. Gene expression levels of ALPL, COL1A1 and SPARC were significantly downregulated by both drugs. Further analysis by ELISA indicated the downregulation of protein levels of ALP, COL1A1 and SPARC in the BEV and SUN groups. The effects of BEV and SUN in HAOBs may be mediated by alterations to osteogenic and catabolic markers. Therapeutic or preventive strategies in MRONJ may address drug-induced depression of osteoblast differentiation.

The Role of Macrophage Migration Inhibitory Factor in Adipose-Derived Stem Cells Under Hypoxia.

Background: Adipose-derived stem cells (ASCs) are multipotent mesenchymal stem cells characterized by their strong regenerative potential and low oxygen consumption. Macrophage migration inhibitory factor (MIF) is a multifunctional chemokine-like cytokine that is involved in tissue hypoxia. MIF is not only a major immunomodulator but also is highly expressed in adipose tissue such as subcutaneous adipose tissue of chronic non-healing wounds. In the present study, we investigated the effect of hypoxia on MIF in ASCs isolated from healthy versus inflamed adipose tissue. Methods: Human ASCs were harvested from 17 patients (11 healthy adipose tissue samples, six specimens from chronic non-healing wounds). ASCs were treated in a hypoxia chamber at <1% oxygen. ASC viability, MIF secretion as well as expression levels of MIF, its receptor CD74, hypoxia-inducible transcription factor-1α (HIF-1α) and activation of the AKT and ERK signaling pathways were analyzed. The effect of recombinant MIF on the viability of ASCs was determined. Finally, the effect of MIF on the viability and production capacity of ASCs to produce the inflammatory cytokines tumor necrosis factor (TNF), interleukin (IL)-6, and IL-1ß was determined upon treatment with recombinant MIF and/or a blocking MIF antibody. Results: Hypoxic treatment inhibited proliferation of ASCs derived from healthy or chronic non-healing wounds. ASCs from healthy adipose tissue samples were characterized by a low degree of MIF secretion during hypoxic challenge. In contrast, in ASCs from adipose tissue samples of chronic non-healing wounds, secretion and expression of MIF and CD74 expression were significantly elevated under hypoxia. This was accompanied by enhanced ERK signaling, while AKT signaling was not altered. Recombinant MIF did stimulate HIF-1α expression under hypoxia as well as AKT and ERK phosphorylation, while no effect on ASC viability was observed. Recombinant MIF significantly reduced the secretion of IL-1ß under hypoxia and normoxia, and neutralizing MIF-antibodies diminished TNF-α and IL-1ß release in hypoxic ASCs. Conclusions: Collectively, MIF did not affect the viability of ASCs from neither healthy donor site nor chronic wounds. Our results, however, suggest that MIF has an impact on the wound environment by modulating inflammatory factors such as IL-1ß.

Anterior-posterior view by full-body digital X-ray to rule out severe spinal injuries in Polytraumatized patients.

BACKGROUND: Spinal injuries are present in 16-31% of polytraumatized patients. Rapid identification of spinal injuries requiring immobilization or operative treatment is essential. The Lodox-Statscan (LS) has evolved into a promising time-saving diagnostic tool to diagnose life-threatening injuries with an anterior-posterior (AP)-full-body digital X-ray. METHODS: We aimed to analyze the diagnostic accuracy and the interrater reliability of AP-LS to detect spinal injuries in polytraumatized patients. Therefore, within 3 years, AP-LS of polytraumatized patients (ISS ≥ 16) were retrospectively analyzed by three independent observers. The sensitivity and specificity of correct diagnosis with AP-LS compared to CT scan were calculated. The diagnostic accuracy was evaluated by using the area under the ROC (receiver operating characteristic curve) for sensitivity and specificity. Interrater reliability between the three observers was calculated using Fleiss' Kappa. The sensitivity of AP-LS was further analyzed by the severity of spinal injuries. RESULTS: The study group included 320 patients (48.5 years ±19.5, 89 women). On CT scan, 207 patients presented with a spinal injury (65%, total of 332 injuries). AP-LS had a low sensitivity of 9% (31 of 332, range 0-24%) and high specificity of 99% (range 98-100%). The sensitivity was highest for thoracic spinal injuries (14%). The interrater reliability was slight (κ = 0.02; 95% CI: 0.00, 0.03). Potentially unstable spinal injuries were more likely to be detected than stable injuries (sensitivity 18 and 6%, respectively). CONCLUSION: This study demonstrated high specificity with low sensitivity of AP-LS in detecting spinal injuries compared to CT scan. In polytraumatized patients, AP-LS, implemented in the Advanced Trauma Life Support-algorithm, is a helpful tool to diagnose life-threatening injuries. However, if spinal injuries are suspected, performing a full-body CT scan is necessary for correct diagnosis.

Tendon-like tether formation for tongue-base advancement in an ovine model using a novel implant device intended for the surgical management of obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is a serious debilitating condition with significant morbidity and mortality affecting almost one billion adults globally. The current gold standard in the non-surgical management of airway collapse is continuous positive airway pressure (CPAP). However, non-compliance leads to a high abandon rate (27-46%). While there are multiple sites of airway obstruction during sleep, the tongue base is recognized as the key player in the pathogenesis of OSA. Poor outcomes of current tongue suspension devices are due to fracture, slippage or migration of devices. Three tongue tethering device groups, namely a polydioxanone/polyurethane combination (PDO + PU) treatment group, a PDO analytical control group, and a polypropylene (PP) descriptive control group, were implanted into 22 sheep (75-85 kg) in a two-phased study. After implant times of 8, 16, and 32 weeks, sheep were serially euthanized to allow for explantation of their tongues and chins. The PDO + PU devices remodeled during the 32-week implant period into a hybrid biological tendon-like tether through the process of gradual degradation of the PDO and collagen deposition as shown by electrophoresis, histology and mechanical testing. The control PDO device degraded completely after 32 weeks and the PP devices remained intact. The hybrid biological tendon-like tether exhibited a break-strength of 60 N, thus exceeding the maximum force to overcome upper airway collapse.

Suitability of the microDiamond detector for experimental determination of the anisotropy function of High Dose Rate 192 Ir brachytherapy sources.

PURPOSE: To investigate the suitability of the microDiamond detector (mDD) type 60019 (PTW-Freiburg, Germany) to measure the anisotropy function F(r,θ) of High Dose Rate (HDR) 192 Ir brachytherapy sources. METHODS: The HDR 192 Ir brachytherapy source, model mHDR-v2r (Elekta AB, Sweden), was placed inside a water tank within a 4F plastic needle. Four mDDs (mDD1, mDD2, mDD3, and mDD4) were investigated. Each mDD was placed laterally with respect to the source, and measurements were performed at radial distances r = 1 cm, 3 and 5 cm, and polar angles θ from 0° to 168°. The Monte Carlo (MC) system EGSnrc was used to simulate the measurements and to calculate phantom effect, energy dependence and volume-averaging correction factors. F(r,θ) was determined according to TG-43 formalism from the detector reading corrected with the MC-based factors and compared to the consensus anisotropy function CON F(r,θ). RESULTS: At 1 cm, the differences between measurements and MC simulations ranged from -0.8% to +0.8% for θ = 0° and from -2.1% to + 2.3% for θ ≠ 0°. At 3 and 5 cm, the differences ranged from +1.4% to +3.9% for θ = 0°, and from -0.4% to +2.9% for θ ≠ 0°. All differences were within the uncertainties (k = 2). At small angles, the phantom effect correction was up to -1.9%. This effect was mainly caused by the air between source and needle tip. The energy correction was angle-independent everywhere. For small angles at 1 cm, the volume-averaging correction was up to -2.9% and became less important for larger angles and distances. The differences of the measured F(r,θ) corrected with the MC-based factors to CON F(r,θ) ranged from -1.0% to +3.4% for mDD1, -2.2% to +4.2% for mDD2, -2.5% to +4.0% for mDD3, and -2.6% to +3.4% for mDD4. All differences were within the uncertainties (k = 2) except one at (3 cm, 0°). For all the mDDs, F(r,0°) was always higher than CON F(r,0°), with average differences of +3.1% (1 cm), +3.6% (3 cm), and +1.9% (5 cm). The inter-detector variability was within 2.9% (1 cm), 1.8% (3 cm), and 3.4% (5 cm). CONCLUSIONS: A reproducible method and experimental setup were presented for measuring and validating F(r,θ) of an HDR 192 Ir brachytherapy source in a water phantom using the mDD. The phantom effect and the volume-averaging need to be taken into account, especially for the smaller distances and angles. Good agreement to CON F(r,θ) was obtained. The discrepancies at (1 cm, 0°), accurately predicted by the MC results, may suggest a reconsideration of CON F(r,θ), at least for this position. The slight overestimations at (3 cm,0°) and (5 cm,0°), both in comparison to CON F(r,θ) and MC results, may be due to an underestimation of the air volume between source and needle tip, dark current, intrinsic over-response of the mDDs, or radiation-induced charge imbalance in the detector's components. The results indicate that the mDD is a valuable tool for measurements with HDR 192 Ir brachytherapy sources and support its employment for the determination and validation of TG-43 parameters of such sources.

Essentials of psychoanalytic process and change: how can we investigate the neural effects of psychodynamic psychotherapy in individualized neuro-imaging?

The paper focuses on the essentials of psychoanalytic process and change and the question of how the neural correlates and mechanisms of psychodynamic psychotherapy can be investigated. The psychoanalytic approach aims at enabling the patient to "remember, repeat, and work through" concerning explicit memory. Moreover, the relationship between analyst and patient establishes a new affective configuration which enables a reconstruction of the implicit memory. If psychic change can be achieved it corresponds to neuronal transformation. Individualized neuro-imaging requires controlling and measuring of variables that must be defined. Two main methodological problems can be distinguished: the design problem addresses the issue of how to account for functionally related variables in an experimentally independent way. The translation problem raises the question of how to bridge the gaps between different levels of the concepts presupposed in individualized neuro-imaging (e.g., the personal level of the therapist and the client, the neural level of the brain). An overview of individualized paradigms, which have been used until now is given, including Operationalized Psychodynamic Diagnosis (OPD-2) and the Maladaptive Interpersonal Patterns Q-Start (MIPQS). The development of a new paradigm that will be used in fMRI experiments, the "Interpersonal Relationship Picture Set" (IRPS), is described. Further perspectives and limitations of this new approach concerning the design and the translation problem are discussed.