Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto.

Background: In the neoadjuvant GeparSixto study, adding carboplatin to taxane- and anthracycline-based chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC). Here, we present survival data and the potential prognostic and predictive role of homologous recombination deficiency (HRD). Patients and methods: Patients were randomized to paclitaxel plus nonpegylated liposomal doxorubicin (Myocet®) (PM) or PM plus carboplatin (PMCb). The secondary study end points disease-free survival (DFS) and overall survival (OS) were analyzed. Median follow-up was 47.3 months. HRD was among the exploratory analyses in GeparSixto and was successfully measured in formalin-fixed, paraffin-embedded tumor samples of 193/315 (61.3%) participants with TNBC. Homologous recombination (HR) deficiency was defined as HRD score ≥42 and/or presence of tumor BRCA mutations (tmBRCA). Results: A significantly better DFS (hazard ratio 0.56, 95% CI 0.34-0.93; P = 0.022) was observed in patients with TNBC when treated with PMCb. The improvement of OS with PMCb was not statistically significant. Additional carboplatin did not improve DFS or OS in patients with HER2-positive tumors. HR deficiency was detected in 136 (70.5%) of 193 triple-negative tumors, of which 82 (60.3%) showed high HRD score without tmBRCA. HR deficiency independently predicted pCR (ypT0 ypN0) [odds ratio (OR) 2.60, 95% CI 1.26-5.37, P = 0.008]. Adding carboplatin to PM significantly increased the pCR rate from 33.9% to 63.5% in HR deficient tumors (P = 0.001), but only marginally in HR nondeficient tumors (from 20.0% to 29.6%, P = 0.540; test for interaction P = 0.327). pCR rates with carboplatin were also higher (63.2%) than without carboplatin (31.7%; OR 3.69, 1.46-9.37, P = 0.005) in patients with high HRD score but no tmBRCA. DFS rates were improved with addition of carboplatin, both in HR nondeficient (hazard ratio 0.44, 0.17-1.17, P = 0.086) and HR deficient tumors (hazard ratio 0.49, 0.23-1.04, P = 0.059). Conclusions: The addition of carboplatin to neoadjuvant PM improved DFS significantly in TNBC. Long-term survival analyses support the neoadjuvant use of carboplatin in TNBC. HR deficiency in TNBC and HRD score in non-tmBRCA TNBC are predictors of response. HRD does not predict for carboplatin benefit.

Patient-Report Satisfaction and Health-Related Quality of Life in TiLOOP® Bra-Assisted or Implant-Based Breast Reconstruction Alone.

INTRODUCTION: Implant-based breast reconstructions (IBBR) using alternatives to acellular dermal matrixes are increasing. Data on complications are limited, and information concerning health-related quality of life (HR-QoL) following the use of these synthetic meshes do not exist. METHODS: Between January 2006 and January 2013, patients undergoing immediate or delayed-immediate IBBR with or without titanium covered polypropylene mesh (TiLOOP® Bra) were investigated. HR-QoL was assessed using the validated self-reporting BREAST-Q questionnaire. Patient demographics and complications were evaluated retrospectively. Stepwise regression backward elimination analysis was performed to identify influential factors on each BREAST-Q domain. RESULTS: Of the 90 women, 42 had IBBR alone and 48 in combination with TiLOOP® Bra. The mean follow-up was 18 months in the TiLOOP® Bra and 17.5 months in the implant alone group (p = 0.827). The overall complication rate was 21.1 %, with 14.6 % in the TiLOOP® Bra and in 28.6 % in the implant alone group (p = 0.105). Capsular contraction rate was 4.4 % in the TiLOOP® Bra and 16.7 % in the implant alone group (p = 0.052). The analysis of the HR-QoL showed no significant differences between the groups. Surgeries prior to IBBR had a positive influence on HR-QoL. TiLOOP® Bra was associated with a negative effect on "satisfaction with breast" (ß = -5.72; p < 0.001), as it was no longer observed for "satisfaction with outcome" and other domains.

Juvenile idiopathic arthritis of the temporomandibular joint - no longer the forgotten joint.

Juvenile idiopathic arthritis (JIA) of the temporomandibular joint (TMJ) is common in children, with an increasing awareness of the condition in all healthcare professionals. TMJ involvement presents a challenge in both diagnosis and treatment, as late presentation can still occur as the disease often develops asymptomatically. This can result in facial deformity and/or functional difficulties including obstructive sleep apnoea. Early diagnosis is therefore essential, requiring a high index of clinical suspicion coupled with the judicious use of gadolinium contrast magnetic resonance imaging (MRI). Long-term management is best provided by a multidisciplinary team as patients often need a combination of pharmacological management, surgical interventions, orthodontics, and psychological support. End stage deformity can be treated by different surgical options, each with their own risks and benefits, however recently there is increasing recognition for the role of total alloplastic TMJ replacement. This review focuses on the diagnosis and management of TMJ arthritis and aims to highlight the important role of maxillofacial surgeons in JIA treatment.

Pegfilgrastim +/- ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study.

BACKGROUND: TAC (docetaxel/doxorubicin/cyclophosphamide) is associated with high incidences of grade 4 neutropenia and febrile neutropenia (FN). This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC. PATIENTS AND METHODS: Patients with stage T2-T4 primary breast cancer were scheduled to receive 6-8 cycles of TAC. Primary prophylaxis was: ciprofloxacin 500 mg orally twice daily on days 5-14 (n = 253 patients; 1478 cycles), daily granulocyte colony-stimulating factor (G-CSF) (filgrastim 5 microg/kg/day or lenograstim 150 microg/m(2)/day) on days 5-10 (n = 377; 2400 cycles), pegfilgrastim 6 mg on day 2 (n = 305; 1930 cycles), or pegfilgrastim plus ciprofloxacin (n = 321; 1890 cycles). RESULTS: Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN (5% and 7% versus 18% and 22% of patients; all P < 0.001), grade 4 neutropenia, and leukopenia. Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN (P < 0.01 versus pegfilgrastim alone) and fatal neutropenic events. CONCLUSION: Ciprofloxacin alone, or daily G-CSF from day 5-10 (as in common practice), provided suboptimal protection against FN and related toxic effects in patients receiving TAC. Pegfilgrastim was significantly more effective in this setting, especially if given with ciprofloxacin.

Dental foundation year 2 training in oral and maxillofacial surgery units - the trainees' perspective.

Most dental foundation year 2 (DF2) training takes place in oral and maxillofacial surgery (OMFS) units. We did a survey of DF2 trainees in these units by telephone interviews and an online questionnaire to find out about their experience of training and their career aspirations. A total of 123 responded, which is roughly 41% of the total estimated number of trainees. Trainees applied for these posts mainly to improve their dentoalveolar skills (50%), and this was cited as the best aspect of the training. Most (81%) were on-call at night and this was generally thought to be a valuable training experience (77%), but 20% thought that it was the worst aspect of the job. Most did not regret taking up the post although the experience had caused 75% to alter their intentions about their future career; general dental practice was the commonest choice. In conclusion, trainees are generally satisfied with their training and these positions have guided their choices about future careers.

A short-term follow-up of implant based breast reconstruction using a titanium-coated polypropylene mesh (TiLoop(®) Bra).

INTRODUCTION: A new approach for implant based breast reconstruction (IBBR) is the use of a titanium-coated polypropylene mesh (TCPM) as an alternative to acellular dermal matrix (ADM). This TCPM has a good biocompatibility and can be used similarly to ADM. The aim of this study is to discuss indications, limitations and complications of TCPM in IBBR. METHODS: A retrospective analysis of 42 patients undergoing immediate or delayed IBBR using a TCPM was performed. Primary endpoints were incidence of infection and expander/implant with mesh removal due to infected fluid collection or extrusion. RESULTS: In two patients, mild hematoma, seroma or infection occurred. Skin necrosis or capsular contraction was observed in one patient. Mesh explantation was needed in 3 cases. These events were higher among the first cases and in patients with postoperative skin infection (p = 0.003). CONCLUSION: In selected patients with adequate soft tissue cover TCPM seems to be a helpful tool for implant stabilization in terms of lateral stabilization and fixation of the musculus pectoralis major. In comparison to ADM, TCPM is cheaper and initial results are promising, but further follow-up data are necessary. In patients with poor soft tissue cover ADM should be used.

A string of enzymes, purification and characterization of a fusion protein comprising the four subunits of the glucose phosphotransferase system of Escherichia coli.

A multidomain protein comprising the four subunits of the glucose phosphotransferase system of Escherichia coli was constructed by fusion of the transmembrane subunit IICBGlc and the three cytoplasmic proteins, IIAGlc, HPr, and enzyme I. The subunits were linked in the above order with Ala-Pro-rich linkers; the fusion protein was overexpressed in E. coli and purified by Ni2+ chelate affinity chromatography. Approximately 3 mg of the fusion protein could be purified from 1 liter of culture. The phosphotransferase activity of the purified fusion protein was 3-4 times higher than that of an equimolar mixture of the isolated subunits. The mannose transporter, which also requires enzyme I and HPr, was not an effective competitor in the overall phosphoryltransfer reaction when the fusion protein was used, whereas it was a competitor when an equimolar mixture of the separate subunits was employed. Transphosphorylation activity of the fusion protein was almost indistinguishable from the wild-type IICBglc. Addition of extra IICBGlc subunit could significantly stimulate the phosphotransferase activity of the fusion protein, addition of extra IIAGlc subunit and enzyme I, in contrast, was slightly inhibitory, and HPr had almost no effect. An optimal detergent-lipid ratio is required for maximum activity of the fusion protein. Our results suggest that Ala-Pro-rich linker sequences may be of general use for the construction of catalytically active fusion proteins with novel properties.