T cell responses in early-stage melanoma patients occur frequently and are not associated with humoral response.

Endogenous tumor-specific T cells are detectable in patients with different tumor types including malignant melanoma (MM). They can control tumor growth, have impact on patient survival and correlate with improved clinical response to immune checkpoint therapy. Thus, they may represent a potent biomarker for respective treatment decisions. So far, major target antigens of endogenous MM-reactive T cells have not been determined systematically. Instead, autoantibodies are discussed as surrogate parameter for MM-specific T cells. Throughout a period of more than 60 days after tumor resection, we therefore determined in 38 non-metastasized primary MM patients and in healthy individuals by IFNγ ELISpot and bead-based fluorescent multiplex assay major target antigens of spontaneous T cell and humoral responses using a broad panel of MM antigens and assessed the presence and suppressive impact of MM-reactive regulatory T cells (Tregs). We show that MM-reactive T cells are frequent in MM patients, transiently increase after tumor removal and are mostly directed against Melan-A/MART-1, Tyrosinase, NA17-A and p53. MM-specific Tregs were only detected in few patients and inhibited MM-reactive T cells particularly early after tumor resection. Tumor-specific autoantibodies occurred in most patients, but did not correlate with T cell responses. Thus, endogenous antibodies may not be reliable surrogate parameters of MM-reactive T cells.

A randomized clinical trial comparing the impact of different oral hygiene protocols and sealant applications on plaque, gingival, and caries index scores.

OBJECTIVE: This prospective randomized clinical trial investigated the impact of different tooth brushing strategies and sealant application on patients with fixed appliances: plaque, gingival, caries index scores, periodontal parameters, microbial, and molecular biological parameters were assessed. MATERIALS AND METHODS: Fifty-five male and 63 female patients aged 11-15 years were enrolled in this 12-week, four-arm parallel-group trial. Patients of group 1 used a Sonicare FlexCare electric brush, patients of group 2 used a manual (elmex interX short head) plus interdental (Curaprox CPS 15) brush, and patients of group 3 and 4 used a manual brush only. The teeth of patients in groups 1, 2, and 3 were sealed with a filled resin (ProSeal). Patients were advised to brush twice daily and measured time spent brushing mornings and evenings [tooth brushing duration (TBD)]. Plaque (PIB, TQHI, MAPI) and gingival index (PBI) as well as caries index (DMFT/DMFS) scores were assessed at baseline and after 4, 8, and 12 weeks. RESULTS AND CONCLUSIONS: TBD did not differ significantly between patients using the electric or manual brush only (between 197 and 209 seconds) but was longer when using the combination of two manual brushes. TBD was slightly longer in the evenings. There was no gender difference. Although TBD was longer for the combination group, we failed to demonstrate any beneficial effect on outcome parameters for this group. No differences between sealed or unsealed tooth surfaces or for use of a manual or electric brush were observed.

Antitumor T cell responses in bladder cancer are directed against a limited set of antigens and are modulated by regulatory T cells and routine treatment approaches.

Regulatory T cells (Tregs) play a key role in cancer immune escape. We identified target antigens of spontaneous tumor-specific T cell responses in urothelial carcinoma (UC) and evaluated their modulation by treatment and Treg. We determined Treg target antigens in UC. Fifty-six UC and 13 control patients were prospectively enrolled. Blood was drawn before and after routine treatment. Changes in Treg frequency were measured by fluorescence cytometry and the T effector cell (Teff) response against a set of nine tumor-associated antigens (TAAs) was monitored with an interferon-gamma ELISpot. Antigen specificity of Treg was determined by their increased capacity to inhibit after TAA-specific activation the proliferation of an autologous T cell population. The highest difference in the overall response rate for the total T cell population was observed for epidermal growth factor receptor (EGFR) (UC: 23% and controls: 0%). After depleting Treg, also new york esophageal (NYES)O1 (19 and 0%) and MUC20 (27 and 0%) were more frequently recognized in UC patients. In metastasized patients, the TAA-directed T cell response was augmented by Treg depletion. Tumor resection seemed to diminish Treg suppression of TAA-specific immunity, whereas chemotherapy had no effect. We demonstrated the existence of TAA-specific Treg in UC, which share antigen specificities with Teff. The coexistence of TAA-specific Treg and Teff was very rare. Treg frequencies in the peripheral blood were not changed by therapy. In summary, we identified potentially immunologically relevant TAA in UC. TAA-specific T cell responses against these antigens are suppressed by Treg. We identified TAA-specific Treg in UC patients, which do not cooccur with TAA-specific Teff.

Prognostic value of the periodontal risk assessment in patients with aggressive periodontitis.

OBJECTIVES: Aim of the study was to evaluate the predictive value of the modified periodontal risk assessment (PRA) in patients with aggressive periodontitis (AgP) for the first time. MATERIAL AND METHODS: A total of 86 Patients with AgP were re-examined 5-17 years after active periodontal treatment. Risk profile according to the modified PRA was assigned and regularity of maintenance monitored. Tooth loss, bone loss and recurrence of periodontitis were analysed in association with gender, diagnosis, compliance and risk profile using uni- and multivariate parametric regression and Cox proportional hazards models. RESULTS: A total of 14 patients showed a localized AgP, 60 a high-risk-profile and 19 were compliant with the proposed maintenance-interval. Of 2202 teeth 98 were lost. Multivariate analysis could not assign a statistically significant impact to risk-profile. By excluding Interleukin-1 composite genotype from the modified PRA a significant influence (p = 0.003, HR 2.74) was detected. The impact of compliance was shown to be nearly significant (p = 0.059, HR 2.0). In patients with generalized AgP a tendency for increased tooth loss was found. CONCLUSION: The prognostic value of the modified PRA could not be confirmed in patients with AgP. However, exclusion of Interleukin-1 composite genotype led to a model with significant influence on tooth loss.

Clinical success rates for polyether crown impressions when mixed dynamically and statically.

The purpose of this study is to compare success rates of dual-viscosity impressions for two types of mixing techniques of the polyether elastomeric impression material. Additionally, influencing parameters on the success rates should be evaluated. The expectation was that there would be no difference between the success rates for the two mixing techniques. Two centres enrolled 290 subjects (727 teeth) into the trial. Patients were randomized for the two types of mixing techniques. One step, dual-viscosity impressions were made with either statically mixed Impregum Soft tray material (SAM) or dynamically mixed Impregum Penta H DuoSoft (DMM). Low viscosity Impregum Garant L DuoSoft was used for both groups. Gingival displacement involved the use of two braided cords. Full-arch trays were used exclusively. Both critical defects and operator errors were assessed for the first impression taken by trained dentists. The primary outcome was impression success. For comparison of the two mixing techniques, the odds ratio for success and the corresponding one-sided 95% confidence interval was calculated by a logistic regression model. To account for the dependence between several teeth within one patient, the method of general estimating equations was used. The overall impression success rate was 35.4%. Both mixing techniques showed equal success rates indicated by an OR of 1.0 and a lower limit of the one-sided 95% confidence interval of 0.71. Using this result to develop the corresponding interval for the difference, it could be shown that the success rate using SAM was at most 8.2% lower than that when using DMM with a probability of 95%. Multivariate logistic regression analysis of other potential influencing factors showed position of finish line (p = 0.008, supra compared to mixed), blood coagulation disorder (p = 0.021) and the level of training of the clinician (student vs dentist, p=0.008) to have an independent influence on the success rate. Dynamic mechanical mixing and the new static mixing of polyether tray material showed nearly equal success rates in the study even though success rates were comparatively low (DMM, 35.3%; SAM, 35.4%).

Effect of the osteotome technique in cases of deficient edentulous ridge.

PURPOSE: The use of dental implants may be limited by lack of sufficient bone. The effectiveness of the alveolar ridge bone-spreading technique in the maxilla was compared with the standard technique. Bone spreading is a technique in which hand osteotomes are used to progressively enlarge the remaining deficient edentulous ridge to enable placement of dental implants. MATERIALS AND METHODS: In the test group (bone spreading), 72 patients received 126 implants. Thirty-six patients with 63 implants placed with conventional implant preparation served as a control group. Measurements of outcome were implant failure and complications after therapy. Kaplan-Meier curves were used to depict time from implant placement to implant failure or complication. RESULTS: Six complications were observed after placement of the implants (3 implant failures, peri-implant inflammation in 2 implants, and 1 exposure of rough implant surface). There was a trend toward more implant failures in the control group. CONCLUSIONS: Results of the ridge-spreading technique seem to be similar to those of the standard technique. However, these results should be regarded with caution because of the small number of complications.

Fiber-reinforced composite fixed dental prostheses: a retrospective clinical examination.

PURPOSE: To obtain survival data on 32 fiber-reinforced fixed dental prostheses which were inserted in our department and to rate the quality of these restorations on the basis of esthetic, biological, and functional parameters. MATERIALS AND METHODS: Thirty-two patients with fiber-reinforced fixed dental prostheses were included in the study. The fiber frameworks were made of a polymer-monomer-preimpregnated continuous unidirectional glass fiber material. The survival times, failure events, and clinical parameters were recorded. Restorations in function without previous failure were classified as "Overall Survival". The classification "Functional Survival" was assigned in the event of minor failure and subsequent repair. Loss of the restoration was regarded as "Failure". The quality rating was performed using modified USHPS/Ryge criteria. RESULTS: The follow-up interval ranged from 2 to 64 months with a median follow-up time of 18.2 months. Twenty-four restorations were classified as "Overall Survival", seven were classified as "Functional Survival", and one was classified as "Failure". The overall survival at the median follow-up time was 74.4%. For the majority, the quality rating (USHPS/Ryge criteria) yielded clinically excellent results in all categories. No restoration was rated as insufficient or poor. CONCLUSION: Fiber-reinforced composite fixed dental prostheses provide sufficient stability and very good esthetic, biological, and functional performance in the case of specific clinical indications.

Experimental study determining the mechanical properties of dental floss holders.

This study determined the mechanical properties of 19 dental floss holders. Eight single-use holders and 11 reusable ones were tested. An in vitro model with dental proximal contact strength of 8 N was created. Every device had to pass the proximal contact 30 times. We measured (1) the displacement of the floss [mm], (2) the force [N] necessary to pass the proximal contact after the 30th passage, (3) the loosening of the floss (offset [mm]), and (4) the change in the distance between the branches [mm]. Each measurement was repeated seven times. The results are displacement of the floss after 30 passages, 2.0 to 9.2 mm; passage force, 2.6 to 11 N; increases in branch distance, 0-2.9 mm; offset of the floss, 0-1.8 mm (all numbers are medians). Based on cleaning a full dentition (30 passages), we suggest introducing minimal requirements of <4 mm for the displacement of the floss, ≥11 N for the force, and <0.1 mm for the difference in branch distance and the offset. Only two products fulfilled our criteria. The tests show that dental floss holders vary extremely in their mechanical properties. Their effective use seems often impossible due to limited mechanical properties.

Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients.

Regulatory CD4+ T cells (Treg) prevent tumor clearance by conventional T cells (Tconv) comprising a major obstacle of cancer immune-surveillance. Hitherto, the mechanisms of Treg repertoire formation in human cancers remain largely unclear. Here, we analyze Treg clonal origin in breast cancer patients using T-Cell Receptor and single-cell transcriptome sequencing. While Treg in peripheral blood and breast tumors are clonally distinct, Tconv clones, including tumor-antigen reactive effectors (Teff), are detected in both compartments. Tumor-infiltrating CD4+ cells accumulate into distinct transcriptome clusters, including early activated Tconv, uncommitted Teff, Th1 Teff, suppressive Treg and pro-tumorigenic Treg. Trajectory analysis suggests early activated Tconv differentiation either into Th1 Teff or into suppressive and pro-tumorigenic Treg. Importantly, Tconv, activated Tconv and Treg share highly-expanded clones contributing up to 65% of intratumoral Treg. Here we show that Treg in human breast cancer may considerably stem from antigen-experienced Tconv converting into secondary induced Treg through intratumoral activation.

Prognostic factors influencing long-term survival of patients undergoing nephron-sparing surgery for nonmetastatic renal-cell carcinoma (RCC) with imperative indications.

BACKGROUND: We assessed the effect of T stage, Fuhrman's grade, multifocality, bilaterality, positive surgical margins, and synchronism of bilateral tumors on cancer-specific survival of patients with nonmetastatic renal-cell carcinoma (RCC) undergoing nephron-sparing surgery for imperative indications. METHODS: We retrospectively analyzed 168 patients who underwent nephron-sparing surgery for imperative RCC indications between 1974 and 2002. A total of 85 patients had bilateral RCCs; in 27 patients, the tumors were multifocal. Multivariate Cox proportional hazards models were fitted to assess the features associated with cancer-specific survival. RESULTS: The median follow-up was 99 months (range, 2-326 months). Patients were followed until January 2008. A total of 52 patients died of their cancer during follow-up. Multivariate analyses of the total group only revealed Fuhrman's grade 3 (hazard ratio [HR] 2.94) and bilateral occurrence of RCC (HR 1.82) as independent prognostic factors. In a subgroup analysis of patients with bilateral occurrence of RCC, we observed a tendency toward positive surgical margins (HR 2.89, P = 0.08) being another negative prognostic factor. There was no difference in cancer-specific survival between patients with synchronous and metachronous bilateral RCC presence (HR 1.08). CONCLUSIONS: Fuhrman's grade 3 and bilateral occurrence of RCC were the only statistically significant prognostic factors for cancer-specific survival in patients undergoing nephron-sparing surgery for imperative indications for nonmetastatic RCC. The presence of sporadic multifocal tumors and the synchronous occurrence of bilateral tumors have no influence on cancer-specific survival, while positive surgical margins may have an impact in the subset of patients with bilateral RCC.

Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma.

BACKGROUND: The enhancer of zeste homolog 2 (EZH2) gene exerts oncogene-like activities and its (over)expression has been linked to several human malignancies. Here, we studied a possible association between EZH2 expression and prognosis in patients with renal cell carcinoma (RCC). METHODS: EZH2 protein expression in RCC specimens was analyzed by immunohistochemistry using a tissue microarray (TMA) containing RCC tumor tissue and corresponding normal tissue samples of 520 patients. For immunohistochemical assessment of EZH2 expression, nuclear staining quantity was evaluated using a semiquantitative score. The effect of EZH2 expression on cancer specific survival (CSS) was assessed by univariate and multivariate Cox regression analyses. RESULTS: During follow-up, 147 patients (28%) had died of their disease, median follow-up of patients still alive was 6.0 years (range 0-16.1 years). EZH2 nuclear staining was present in tumor cores of 411 (79%) patients. A multivariate Cox regression analysis revealed that high nuclear EZH2 expression was an independent predictor of poor CSS (> 25-50% vs. 0%: HR 2.72, p = 0.025) in patients suffering from non-metastatic RCC. Apart from high nuclear EZH2 expression, tumor stage and Fuhrman's grading emerged as significant prognostic markers. In metastatic disease, nuclear EZH2 expression and histopathological subtype were independent predictive parameters of poor CSS (EZH2: 1-5%: HR 2.63, p = 0.043, >5-25%: HR 3.35, p = 0.013, >25%-50%: HR 4.92, p = 0.003, all compared to 0%: HR 0.36, p = 0.025, respectively). CONCLUSIONS: This study defines EZH2 as a powerful independent unfavourable prognostic marker of CSS in patients with metastatic and non-metastatic RCC.

Differences in lightness, chroma, and hue in the anterior teeth of quinquagenarians and septuagenarians.

The purpose of this study was to evaluate, for both genders and two elderly age groups, differences in lightness, chroma, and hue of pairs of natural anterior teeth, so that more accurate information on color would be available for the production of dentures with a natural appearance. The subjects in the younger group (YG) were 54 to 56 years of age, those in the older group 73 to 75 (N = 195, 48% women). Tooth color was measured using a spectrophotometer. Mixed models were calculated for each pair of teeth, with gender as a fixed factor. Gender did not have a significant effect in either age group. In both groups, differences in chroma between upper canines and lateral incisors and in lightness and hue between upper and lower canines were observed. In the YG, additional differences were found, with the only exception of the comparison between upper central and lateral incisors. The nongender-specific color differences observed should be considered when producing denture teeth for these groups of patients, in order to come as close as possible to the natural color ideal.

Correlation of positioning and clinical results in Oxford UKA.

In a prospective clinical study, 59 patients with anteromedial osteoarthritis of the knee (61 knee joints) underwent minimally invasive medial Oxford unicompartmental arthroplasty phase 3. Clinical and radiographic examinations of 56 knees were carried out at five (4-7) years. American Knee Society (AKS) scores improved from mean 45.5 (20-80) points (knee score) and 55 (15-100) points (function score) before surgery to 90 (30-100) points in both scores after surgery. The position of each implant was determined on screened radiographs using an image intensifier. The implant position was analysed according to the Oxford X-ray rating system. We evaluated nine measures, and there was no detectable correlation between implant position and clinical result. However, long-term studies are needed before it is possible to elaborate an evidence-based guideline on positioning.

Three-body wear of resin denture teeth with and without nanofillers.

STATEMENT OF PROBLEM: The wear behavior of newly developed denture teeth with nanofillers may be different from teeth with other chemical formulations. PURPOSE: The purpose of this study was to examine the 3-body wear resistance of 11 different commercially available resin denture teeth. MATERIAL AND METHODS: The materials tested were conventional (SR Orthotyp PE, Orthognath) and cross-linked acrylic resin teeth without inorganic fillers (Premium 8, SR Postaris DCL, Trubyte Portrait, Artiplus), composite resin teeth with inorganic fillers (SR Orthosit PE, Vitapan), and composite resin teeth (experimental materials) with inorganic nanofillers (NC Veracia Posterior, e-Ha, Mondial). Human enamel and a ceramic denture tooth (Lumin Vacuum) were used as reference materials. The 3-body wear test was performed in a wear machine developed by the Academic Center for Dentistry Amsterdam (ACTA), with millet suspension acting as an abrasive medium (n=10, test load: 15 N, slip rate: 20%, number of cycles: 100,000). Wear was determined with the aid of a profilometer. Data were analyzed with the Kruskal-Wallis test and Mann-Whitney U test using the closed testing approach (significance level for familywise error rate, alpha=.05). RESULTS: None of the acrylic and composite resin materials tested in this study demonstrated the 3-body wear resistance of ceramic teeth or human enamel. Teeth with inorganic fillers demonstrated significantly lower wear values than conventional or cross-linked acrylic resin teeth without fillers. Composite resin teeth with traditional fillers showed significantly lower wear than composite resin teeth with nanofillers. CONCLUSIONS: Denture teeth with and without inorganic fillers differed significantly with regard to the degree of wear generated in the ACTA wear simulator. The incorporation of nanofillers did not improve the wear resistance compared to teeth with traditional fillers.

Functional midterm outcome in 131 consecutive cases of surgical clubfoot treatment.

INTRODUCTION: Since introduction and widespread use of the Ponseti method in the last decade, the need for surgical treatment of clubfeet is nowadays limited to resistant cases. In the time before, surgery via dorsomedial release was a very common treatment option. METHOD: Very few long-term follow-up studies cover the outcome of surgical methods, which is particularly interesting, as clinical results rather worsen with time. In the present study, 98 children (131 clubfeet), who underwent surgical correction using the Imhauser method at the age of 4.5 months were included. Follow-up time was 8.2 years (0-11.8 years) at average. RESULTS: Data could be retrieved from 46 patients (71 feet), only 5 patients (7 feet) were lost to follow-up. The rate of relapses was high, as 47 patients (53 feet) needed surgical revision for recurrence, while clinical scores showed a good result in the Laaveg and Ponseti Score and the Foot-Function-Index. Isokinetic testing and clinical data indicated a significant weakness of the treated foot, when compared to the healthy side in 12 patients with unilateral deformity. The presented study supports like others the issue that the clinical outcome of a surgical, posteromedial release in terms of relapses is disappointing. This fact is apparently not sufficiently reflected in the current clinical scores, which showed rather good results. CONCLUSION: As the question of evaluation methods for results of clubfoot treatment remains controversial, isokinetic testing is an easy to use alternative that provides detailed information about functional limitations and may help in reducing the need for repeated radiographic examinations.

Perinephric and renal sinus fat infiltration in pT3a renal cell carcinoma: possible prognostic differences.

OBJECTIVE: To evaluate the influence of perinephric (PN) and renal sinus (RS) fat infiltration on cancer-specific survival beyond other prognostic factors, as the Tumour-Node-Metastasis (TNM) classification system defines stage T3a renal cell carcinoma (RCC) as infiltration of perirenal fat and/or direct infiltration of the adrenal gland. Perirenal fat invasion is differentiated into RS and PN fat infiltration, but not further classified for the prognosis. PATIENTS AND METHODS: From 1990 to October 2007 106 patients with advanced RCC (T3a) were followed prospectively at one academic centre; all had a radical nephrectomy. To identify prognostic effects of PN, RS or RS + PN fat infiltration, univariable and multivariable Cox proportional hazard regression models were applied, including lymph node status, metastases, presence of sarcomatoid features and tumour necrosis, Fuhrman's grade, Karnofsky performance status, and tumour size. RESULTS: PN fat invasion alone was present in 58, RS in 21, and PN + RS in 27 patients. The median follow-up was 2.9 years; 49 patients died from RCC. In univariable and multivariable analyses RS fat infiltration was an unfavourable prognostic factor (adjusted hazard ratio, HR, 2.24, P = 0.019). Univariable analysis of RS + PN fat infiltration showed the worst prognostic effect (HR 3.25, P < 0.001). In multivariable analysis this combination was an independent prognostic factor (HR 2.75, P = 0.007), as was the presence of metastasis (HR 5.64, P < 0.001). In this group of RS + PN fat infiltration the 5-year cancer-specific survival was 31%. CONCLUSION: Univariable and multivariable analyses showed that the combination of RS and PN fat infiltration is an independent unfavourable prognostic marker. We recommend that perirenal fat infiltration should be further differentiated into RS fat or PN infiltration in the TNM classification. This will better stratify patient prognosis and might allow those in need of adjuvant therapy to be identified.

Is the body mass index a predictor of adverse outcome in prostate cancer after radical prostatectomy in a mid-European study population?

OBJECTIVES: To evaluate the effect of body mass index (BMI) on the histopathological and clinical outcome in prostate cancer. PATIENTS AND METHODS: In a prospective urological cancer database, 620 patients with prostate cancer had a radical prostatectomy (RP) as a curative treatment. The patients were categorized into three groups of BMI (kg/m(2)); 25.0-30.0 (343, 'overweight') and >30.0 (87, 'obese'). We evaluated the histopathological features and the clinical follow-up after RP. The median (range) age of the men was 64.4 (41.1-80.1) years and the median follow-up 5.5 (0.1-15.1) years. The preoperative median prostate-specific antigen (PSA) levels for normal, overweight and obese patients were 9.0 (0.3-133.0), 8.9 (0.4-230.0) and 9.2 (0.5-194.0) ng/mL, respectively. RESULTS: Serum PSA levels were no different among the three groups (P = 0.92). The normal, overweight and obese patients had organ-confined prostate cancer in 53.7%, 57.1% and 58.6%, respectively (P = 0.34) and had lymph node metastases in 7.9%, 7.6% and 4.6% (P = 0.58). Tumour grading was no different for the three groups (P = 0.25). The PSA recurrence-free, prostate cancer-specific and overall survival for the three BMI groups did not differ significantly (each P > 0.05). CONCLUSION: The BMI cannot be shown to be a predictor of adverse prognosis either for histopathological features or for the clinical outcome, e.g. PSA-free, prostate cancer-specific and overall survival, in a mid-European study population after RP.

Substantial reduction of inappropriate tablet splitting with computerised decision support: a prospective intervention study assessing potential benefit and harm.

BACKGROUND: Currently ambulatory patients break one in four tablets before ingestion. Roughly 10% of them are not suitable for splitting because they lack score lines or because enteric or modified release coating is destroyed impairing safety and effectiveness of the medication. We assessed impact and safety of computerised decision support on the inappropriate prescription of split tablets. METHODS: We performed a prospective intervention study in a 1680-bed university hospital. Over a 15-week period we evaluated all electronically composed medication regimens and determined the fraction of tablets and capsules that demanded inappropriate splitting. In a subsequent intervention phase of 15 weeks duration for 10553 oral drugs divisibility characteristics were indicated in the system. In addition, an alert was generated and displayed during the prescription process whenever the entered dosage regimen demanded inappropriate splitting (splitting of capsules, unscored tablets, or scored tablets unsuitable for the intended fragmentation). RESULTS: During the baseline period 12.5% of all drugs required splitting and 2.7% of all drugs (257/9545) required inappropriate splitting. During the intervention period the frequency of inappropriate splitting was significantly reduced (1.4% of all drugs (146/10486); p = 0.0008). In response to half of the alerts (69/136) physicians adjusted the medication regimen. In the other half (67/136) no corrections were made although a switch to more suitable drugs (scored tablets, tablets with lower strength, liquid formulation) was possible in 82% (55/67). CONCLUSION: This study revealed that computerised decision support can immediately reduce the frequency of inappropriate splitting without introducing new safety hazards.

Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial).

A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56-70 Gy in 5.5-7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4-72.2%), after 42 months was 56.5% (95% CI, 44.2-68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9-55.0%); after 42 months, 41.3% (95% CI, 29.3-53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good responders after ICHT had also a good general outcome with relatively rare severe late toxicities. Due to a slight increase of relevant late dysphagia, functional outcome regarding swallowing and tracheotomy free breathing should be more focused in future larynx organ preservation trials.

Occlusal status and prevalence of occlusal malocclusion traits among 9-year-old schoolchildren.

The aim of this study was to provide detailed information concerning clinically relevant occlusal traits and the prevalence of occlusal anomalies in an orthodontically relevant period of dental development. Four hundred and ninety-four German schoolchildren (237 males and 257 females), median age 9 years, were orthodontically examined. Overjet and overbite were measured to the nearest 0.5 mm, and sagittal molar relationships were registered clinically to the nearest quarter unit. In addition, crossbites, scissor bites, and midline displacements were evaluated. Descriptive statistics was complemented by testing gender differences and differences between groups with Class I and Class II anomalies (Mann-Whitney U-test) as well as a statistical evaluation of differences between the three dental stages (Kruskal-Wallis test). Overjet exhibited an extreme range between -2 and 12 mm (median values 3-3.5 mm). An increased overjet was more prevalent than a reduced or reverse overjet, and a severely increased overjet greater than 6 mm was a common finding affecting around 5-10 per cent of the children. Similarly, overbite showed considerable variations of between -1 and 9 mm (medians 3-3.5 mm) and males exhibited a significantly larger overbite than females. In Class II malocclusion subjects, overbite was significantly enlarged (on average between 0.5 and 1 mm) when compared with those with a Class I malocclusion. Traumatic contact of the gingiva affected every 14th child. A Class II molar relationship of three-quarter units or more was a frequent finding affecting more than one child in five. In addition, at 9 years of age, 3 per cent of the children exhibited a Class III molar relationship of at least a half unit. The wide range of orthodontically relevant occlusal traits found in the present study underlines the need for orthodontic screening at 9 years of age (or earlier).