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Stefanie de Groot,1 Leoni A Louwé,2 Ashna IE Ramautar,1 Johanneke EA Portielje,1,3 Aernout C Ogilvie,4 Erdogan Batman,5 Marta Fiocco,6,7 Judith R Kroep1 1Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands; 2Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands; 3Department of Medical Oncology, Haga Hospital, Den Haag, the Netherlands; 4Department of Medical Oncology, OLVG Hospital, Amsterdam, the Netherlands; 5Department of Medical Oncology, Alrijne Hospital, Leiden, the Netherlands; 6Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands; 7Mathematical Institute, Leiden University, Leiden, the Netherlands Background: Oocyte and embryo cryopreservation, using controlled ovarian stimulation (COS), are common fertility preservation methodologies in breast cancer patients receiving gonadotoxic neo (adjuvant) chemotherapy (CT). The effects of COS and peak estradiol levels on CT-induced side effects are unknown.Patients and methods: Eighteen patients with stage II and III breast cancer underwent oocyte or embryo cryopreservation at Leiden University Medical Center before receiving docetaxel, adriamycin, and cyclophosphamide (TAC) CT (COS group). A control group (N=18) was retrospectively selected from breast cancer patients, aged between 18 and 40, who underwent TAC CT without fertility preservation. CT -induced toxicity in the 2 groups was compared using χ2 analysis. Associations between peak estradiol levels and distinct stimulation protocols and side effects in the COS group were investigated by using regression analysis.Results: Patient characteristics between both groups were similar, except for a lower age in the COS group vs the control group (30.5 vs 35.2 years, P=0.005). No differences were seen in grade III/IV side effects between both groups. In the COS group, an increase in thrombopenia grade I/II was seen, while grade I/II stomatitis and constipation were significantly lower in the COS group as compared with the control group (P=0.006 and P=0.008, respectively). In the COS group, no association was found between the peak estradiol levels and distinct stimulation protocols and side effects of CT.Conclusion: COS prior to TAC CT was not associated with an increase in grade III/IV side effects. Interestingly, COS may have a protective effect on mucositis and constipation. Moreover, the peak estradiol levels and distinct stimulation protocols had no effect on grade III/IV side effects in our study. Keywords: chemotherapy, toxicity, fertility preservation, controlled ovarian hyperstimulation

Stefanie de Groot,1 Hans Gelderblom,1 Marta Fiocco,2,3 Judith VMG Bovée,4 Jacobus JM van der Hoeven,1 Hanno Pijl,5 Judith R Kroep1 1Department of Medical Oncology, 2Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 3Mathematical Department, Leiden University, 4Department of Pathology, 5Department of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands Background: Activation of the insulin-like growth factor 1 (IGF-1) pathway is involved in cell growth and proliferation and is associated with tumorigenesis, tumor progression, and therapy resistance in solid tumors. We examined whether variability in serum levels of IGF-1, IGF-2, and IGF-binding protein 3 (IGF-BP3) can predict event-free survival (EFS) and overall survival (OS) in Ewing sarcoma patients treated with chemotherapy.Patients and methods: Serum levels of IGF-1, IGF-2, and IGF-BP3 of 22 patients with localized or metastasized Ewing sarcoma treated with six cycles of vincristine/ifosfamide/doxorubicin/etoposide (VIDE) chemotherapy were recorded. Baseline levels were compared with presixth cycle levels using paired t-tests and were tested for associations with EFS and OS. Continuous variables were dichotomized according to the Contal and O’Quigley procedure. Survival analyses were performed using Cox regression analysis.Results: High baseline IGF-1 and IGF-BP3 serum levels were associated with EFS (hazard ratio [HR] 0.075, 95% confidence interval [CI] 0.009–0.602 and HR 0.090, 95% CI 0.011–0.712, respectively) in univariate and multivariate analyses (HR 0.063, 95% CI 0.007–0.590 and HR 0.057, 95% CI 0.005–0.585, respectively). OS was improved, but this was not statistically significant. IGF-BP3 and IGF-2 serum levels increased during treatment with VIDE chemotherapy (P=0.055 and P=0.023, respectively).Conclusion: High circulating serum levels of IGF-1 and IGF-BP3 and the molar ratio of IGF-1:IGF-BP3 serum levels were associated with improved EFS and a trend for improved OS in Ewing sarcoma patients treated with VIDE chemotherapy. These findings suggest the need for further investigation of the IGF-1 pathway as a biomarker of disease progression in patients with Ewing sarcoma. Keywords: Ewing sarcoma, chemotherapy, IGF-1, IGF-2, IGF-BP3, IGF-1R, survival, biomarkers

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1468-0114.2009.01358.x Byline: M. ORESTE FIOCCO (1) Abstract: Abstract Some have concluded that the only appropriate response to the problem of temporary intrinsics is the view that familiar, concrete objects persist through time by perduring, that is, by having temporal parts. Many, including myself, believe this view of persistence is false, and so reject this conclusion. However, the most common attempts to resolve the problem and yet defend the view that familiar, concrete objects endure are self-defeating. This has heretofore gone unnoticed. I consider the most familiar such attempts, based on a strategy called tensing the copula, and present a general argument to demonstrate why this strategy - and any strategy based on relativization- fails. I then show how the considerations raised in this general argument undermine other attempts to resolve the problem while denying perdurance. All these attempts are undermined by an assumption essential to the problem of temporary intrinsics, to wit, that there are many moments of time and all have the same ontological status. As long as this assumption is maintained, the only solution to the problem is that familiar, concrete objects perdure. Thus, in order to defend the view that objects persist through time by enduring, one must adopt a different metaphysics of time (viz., presentism). I conclude that it is neither unreasonable nor impracticable to do so. Author Affiliation: (1)Department of PhilosophyUniversity of California, Irvine

Purpose: The purpose of this study was to determine and compare the percentage of completely healed meniscal tears after arthroscopic repair combined with anterior cruciate ligament reconstruction (ACLR) for the different vascular zones of the meniscus.Methods: PubMed, Embase, Web of Science, Cochrane library and Emcare were searched on 19 May 2020 for articles reporting healing rates after arthroscopic meniscal repair with concomitant ACLR for the different meniscal vascular zones as assessed by second-look arthroscopy. Data on meniscal tears were extracted as located in zones 1, 2 or 3, according to the Cooper classification. Studies were graded in quality using a modified Newcastle-Ottawa Scale. Pooled analyses were performed utilizing a random-effects model. Meta-analyses were performed using R version 3.6.2 and SPSS statistical software version 25.0. The study was registered with PROSPERO (ID:CRD42020176175).Results: Ten observational cohort studies met the inclusion criteria, accounting for 758 meniscal tear repairs in total. The pooled overall proportion of healing was 78% (95% CI 72-84%). The mean weighted proportion of healing was 83% (95% CI 76-90%) for studies (n = 10) reporting zone 1 tears and 69% (95% CI 59-79%) for studies (n = 9) reporting zone 2 tears. No study reported healing rates for zone 3 tears. The pooled overall odds ratio was 2.5 (95% CI 1.00-6.02), indicating zone 1 tears as 2.5 times more likely to heal than zone 2 tears.Conclusion: This study demonstrates that meniscal tears localized in vascular zone 1 were more likely to heal than those in zone 2.Level Of Evidence: IV. [ABSTRACT FROM AUTHOR]

An increasing number of patients with medication-related osteonecrosis of the jaws (MRONJ) has recently been reported. It is still being debated whether the presence or placement of dental implants can lead to MRONJ, so the aim of this study was to find out whether dental implants are a risk factor for MRONJ. From January 2003-January 2019 180 patients with MRONJ were seen at the Leiden University Medical Center. Luxating moments for the onset of MRONJ were calculated retrospectively. We collected clinical data and details of antiresorptive medication and found 22 patients with both dental implants and MRONJ. In 18 patients the implants were in the region of the MRONJ and they were included in this study, 14 who had had implants before using antiresorptive drugs and four who had had antiresorptive drugs before or at the time that the implants were placed. The median times between the placement of implants and the diagnosis of MRONJ in these two groups were 24 months and 6 months, respectively. Among the 47 implants, 30 were located in the necrotic region, and all 30 were either lost spontaneously or had to be removed during treatment of MRONJ. Our results show an increased risk for developing MRONJ in patients with dental implants. Both peri-implantitis around previously placed implants, and insertion of dental implants, are risk factors. Prevention of peri-implantitis and caution when inserting dental implants in patients who take antiresorptive medication are therefore important. [ABSTRACT FROM AUTHOR]

Background: Improved survival rates for patients with primary bone tumors of the extremities have increased the demand for reliable and durable reconstruction techniques. Some authors have stated that, after successful ingrowth, allografts are a durable long-term solution. This hypothesis is largely based on small studies with short-to-midterm follow-up. In order to determine the durability of intercalary allograft reconstructions in the lower extremities, we evaluated the long-term clinical outcomes at a minimum of 10 years.Methods: All patients who received an intercalary allograft reconstruction in a lower extremity between 1980 and 2006 were included in this retrospective multicenter cohort study. One hundred and thirty-one patients with a median age of 19 years were included. Eighty-nine (68%) had a femoral reconstruction, and 42 (32%) had a tibial reconstruction. The most prevalent diagnoses were osteosarcoma (55%), Ewing sarcoma (17%), and chondrosarcoma (12%). The median follow-up was 14 years. A competing risk model was employed to estimate the cumulative incidences of mechanical failure and infection. Patient mortality or progression of the disease was used as a competing event.Results: Nonunion occurred in 21 reconstructions (16%), after a median of 16 months, and was associated with intramedullary nail-only fixation (p < 0.01) and fixation with nonbridging plate(s) (p = 0.03). Allograft fracture occurred in 25 reconstructions (19%) after a median of 42 months (range, 4 days to 21.9 years). Thirteen (52%) of the allograft fractures occurred within 5 years; 8 (32%), between 5 and 10 years; and 4 (16%), at >10 years. With failure for mechanical reasons as the end point, the cumulative incidences of reconstruction failure at 5, 10, and 15 years were 9%, 14%, and 21%, respectively.Conclusions: Intercalary allograft reconstruction is an acceptable reconstructive option, mainly because of the absence of superior alternatives with a known track record. However, a considerable and continuing risk of mechanical complications should be taken into account.Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

The aim of this retrospective cohort study was to evaluate the relative amount of cancellous bone in the mandibular ramus as a predictor of lingual fracture patterns after bilateral sagittal split osteotomy (BSSO). The study including 78 consecutive patients (156 osteotomy sites). In preoperative cone-beam computed tomographic (CT) scans, the volumes of cancellous and cortical bone in the BSSO surgical field were estimated. Patients were divided into two groups based on the cancellous:cortical bone ratio. We studied postoperative cone-beam CT scans for lingual fracture lines and subcategorised them according to the lingual split scale (LSS). Generalised linear mixed models (GLMM) were estimated to evaluate the association between the cancellous:cortical bone ratio and the lingual fracture pattern. There was a significant association between the cancellous:cortical bone ratio of the mandibular angle and the lingual fracture pattern after BSSO. Mandibular angles with a relatively small amount of cancellous bone showed significantly more LSS3 fracture lines (OR = 1.990, 95%CI 1.043 to 3.796, p = 0.043). These mandibular angles also showed more unfavourable fractures (LSS4), although this was not significant (OR = 2.352, 95%CI 0.748 to 7.392, p = 0.143). The relative amount of cancellous bone in the mandibular angle is significantly associated with the lingual fracture line after BSSO. [ABSTRACT FROM AUTHOR]

"Thing" in the titular question of this paper should be construed as having the utmost generality. In the relevant sense, a thing just is an entity, an existent, a being. The present task is to say what a thing of any category is. This task is the primary one of any comprehensive and systematic metaphysics. Indeed, an answer provides the means for resolving perennial disputes concerning the integrity of the structure in reality—whether some of the relations among things are necessary merely given those relata themselves—and the intricacy of this structure—whether some things are more or less fundamental than others. After considering some reasons for thinking the generality of the titular question makes it unanswerable, the paper propounds the methodology, original inquiry, required to answer it. The key to this methodology is adopting a singular perspective; confronting the world as merely the impetus to inquiry, one can attain an account of what a thing must be. Radical ontology is a systematic metaphysics—broadly Aristotelian, essentialist, and nonhierarchical—that develops the consequences of this account. With it, it is possible to move past stalemate in metaphysics by revealing the grounds of a principled choice between seemingly incommensurable worldviews. [ABSTRACT FROM AUTHOR]

In this retrospective study we investigated the long-term survival of autotransplanted premolars and molars with incompletely developed roots. The presence of the transplanted teeth and their outcome after autotransplantation was ascertained from clinical and radiographic evaluation by a maxillofacial surgeon or dentist. Kaplan Meier survival curves were estimated for the total population and for the two groups (premolars and molars). Fifty-one patients with 74 transplanted teeth were included, and the median duration of follow-up was 10 (range 1–20) years. Four of 66 premolars and one of 8 molars were removed and the cumulative survival was 95.4% (95% CI 90.3 to 100). The difference in survival between the premolars and molars was not significant. These results show that the long-term survival of autotransplanted teeth is good. Replacement of a single tooth by autotransplantation should therefore always be considered and is preferred when a suitable donor tooth is available. [ABSTRACT FROM AUTHOR]

Background: A survival estimation for patients with symptomatic long bone metastases (LBM) is crucial to prevent overtreatment and undertreatment. This study analyzed prognostic factors for overall survival and developed a simple, easy-to-use prognostic model.Methods: A multicenter retrospective study of 1,520 patients treated for symptomatic LBM between 2000 and 2013 at the radiation therapy and/or orthopaedic departments was performed. Primary tumors were categorized into 3 clinical profiles (favorable, moderate, or unfavorable) according to an existing classification system. Associations between prognostic variables and overall survival were investigated using the Kaplan-Meier method and multivariate Cox regression models. The discriminatory ability of the developed model was assessed with the Harrell C-statistic. The observed and expected survival for each survival category were compared on the basis of an external cohort.Results: Median overall survival was 7.4 months (95% confidence interval [CI], 6.7 to 8.1 months). On the basis of the independent prognostic factors, namely the clinical profile, Karnofsky Performance Score, and presence of visceral and/or brain metastases, 12 prognostic categories were created. The Harrell C-statistic was 0.70. A flowchart was developed to easily stratify patients. Using cutoff points for clinical decision-making, the 12 categories were narrowed down to 4 categories with clinical consequences. Median survival was 21.9 months (95% CI, 18.7 to 25.1 months), 10.5 months (95% CI, 7.9 to 13.1 months), 4.6 months (95% CI, 3.9 to 5.3 months), and 2.2 months (95% CI, 1.8 to 2.6 months) for the 4 categories.Conclusions: This study presents a model to easily stratify patients with symptomatic LBM according to their expected survival. The simplicity and clarity of the model facilitate and encourage its use in the routine care of patients with LBM, to provide the most appropriate treatment for each individual patient.Level Of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]