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The majority of enantioselective organocatalytic reactions occur in apolar or weakly polar organic solvents. Nevertheless, the influence of solute-solvent van der Waals forces on the relative kinetics of competitive pathways remains poorly understood. In this study, we provide a first insight into the nature and strength of these interactions at the transition state level using advanced computational tools, shedding light into their influence on the selectivity. In addition, we introduce a series of computational tools tailored for detailed exploration of the role of the organic solvent across diverse research disciplines. As a case study, we selected a highly relevant asymmetric organocatalytic transformation catalyzed by a chiral Brønsted acid. Our analysis reveals that strong dispersion interactions exist between the transition state and the solvent, predominantly involving specific groups of the catalyst rather than being uniformly distributed around the solute. Short-range repulsion between the transition state and the solvent often counteracts the effect of these dispersion forces on the transition state energy, resulting in a minimal overall influence of solute-solvent van der Waals forces on enantioselectivity. However, for certain geometric configurations of the transition states, the effect these interactions remains significant, favoring specific reaction channels. These results suggest that integrating solvent structural and electronic information into catalyst design strategies could offer new avenues for tuning selectivity of organocatalytic processes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background/objectives: HER2-positive breast cancer (HER2 + BC) is an aggressive subtype, with neoadjuvant treatment (NAT) aiming to achieve a pathological complete response (pCR) to improve long-term outcomes. Trastuzumab emtansine (T-DM1) has been established as the standard of care in the adjuvant setting for HER2 + BC patients who do not obtain pCR. The ATD study aimed to evaluate the real-world tolerability of T-DM1 in this setting. The secondary objective was to assess the effectiveness., Methods: This was a multicenter, retrospective study across 24 Italian oncology centers, including 410 patients with HER2 + BC treated with adjuvant T-DM1 following a lack of pCR after NAT. Patient characteristics, NAT regimens, and surgical outcomes were recorded. Tolerability was assessed by documenting adverse events (AEs) according to the CTCAE (v5.0). Preliminary effectiveness was evaluated in terms of relapse-free survival (RFS) and overall survival (OS)., Results: Overall, 228 patients (55.6%) experienced at least one AE related to T-DM1, with 4.9% experiencing grade 3 or higher AEs. The most common AEs were hepatotoxicity (18.5%) and thrombocytopenia (17.6%). T-DM1 was discontinued in 10.0% of patients due to toxicity. After a median follow-up of 25 months, 31 relapse events (7.6%) and 22 deaths (5.4%) were reported. The preliminary incidence of RFS and OS events was similar between patients who completed the T-DM1 course and those who discontinued it early., Conclusions: T-DM1 demonstrated a manageable safety profile, and the adverse events were consistent with those reported in randomized trials. The data are not yet sufficient to allow for a formal analysis of RFS and OS, and long-term follow-up is required.

Data about biosimilar Peg-filgrastim (bioPEG) in autologous stem cell transplant (ASCT) are still scarce. The aim of this study has been to assess efficacy and safety of bioPEG among lymphoma and myeloma patients undergoing ASCT, comparing these data with historical controls receiving other G-CSFs. Furthermore, an economic evaluation has been included to estimate the savings by using bioPEG. This is a prospective cohort study comparing lymphoma and myeloma patients undergoing ASCT and receiving bioPEG (n = 73) with three historical consecutive cohorts collected retrospectively who received other G-CSFs (Lenograstim - Leno - n = 101, biosimilar Filgrastim - bioFIL n = 392, and originator Peg-filgrastim - oriPEG n = 60). We observed a significantly shorter time to neutrophils and platelet engraftment (p < 0.001) in patients treated with bioPEG and oriPEG. Moreover, patients who received bioPEG showed a shorter hospitalization time (p < 0.001) and a lower transfusion need (p < 0.001). We did not observe any significant difference in terms of transplant-related mortality, mucositis, and diarrhea among the four groups. No serious adverse events were associated with bioPEG. Similar data were obtained after running a stratified analysis for lymphomas and myeloma separately conducted by using a propensity score matching. The average total cost per patient of bioPEG was € 18218.9 compared to € 23707.8, € 20677.3 and € 19754.9 of Leno, oriPEG, and bioFIL, respectively. In conclusion, bioPEG seems to be as effective as the originator and more effective than short-acting G-CSFs in terms of post-transplant engraftment in myeloma and lymphoma patients undergoing ASCT. Moreover, bioPEG was cost-effective when compared with the other G-CSFs., (© 2024. The Author(s).)

Introduction: In breast cancer patients, endocrine therapy may exert a negative impact on sexual functioning in both genders, with potentially relevant consequences concerning quality of life and treatment adherence. The availability of effective interventions to maintain and/or restore sexual health in breast cancer patients is a key issue to a research agenda., Objectives: To summarize and critically discuss the most updated and qualitatively relevant literature on the therapeutic approach to sexual impairment in breast cancer patients, with a focus on patients treated with endocrine therapy., Methods: We searched PubMed from its inception to February 2022 for observational and intervention trials including participants with sexual dysfunctions. We were particularly interested in studies of breast cancer patients with sexual dysfunctions while undergoing endocrine therapy. We developed a search strategy with the aim of maximizing the number of articles considered for screening and potential inclusion., Results: Forty-five studies were selected: 3 observational and 42 intervention studies. Thirty-five studies were exclusively focused on female breast cancer populations. We could not identify studies exclusively focused on or also including male breast cancer patients. Overall, in female patients, the available armamentarium encompasses vaginal lubricants, moisturizers, estrogens, dehydroepiandrosterone, CO2 laser, ospemifene, and counseling. None of these interventions has been demonstrated to completely solve sexual dysfunctions when singularly considered. More favorable outcomes have come from the combination of different therapies., Conclusion: In female breast cancer, future research is oriented toward the gain of evidence on combined therapies and long-term data on safety issues on the most promising interventions. The lack of evidence on sexual disturbances in male breast cancer patients remains a major concern., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

The Unitary Group Adapted State-Specific Multi-Reference Perturbation Theory (UGA-SSMRPT2) developed by Mukherjee et al. [J. Comput. Chem. 36, 670 (2015)] has successfully realized the goal of studying bond dissociation in a numerically stable, spin-preserving, and size-consistent manner. We explore and analyze here the efficacy of the UGA-SSMRPT2 theory in the description of the avoided crossings and interlacings between a manifold of potential energy curves for states belonging to the same space-spin symmetry. Three different aspects of UGA-SSMRPT2 have been studied: (a) We introduce and develop the most rigorous version of UGA-SSMRPT2 that emerges from the rigorous version of UGA-SSMRCC utilizing a linearly independent virtual manifold; we call this the "projection" version of UGA-SSMRPT2 (UGA-SSMRPT2 scheme P). We compare and contrast this approach with our earlier formulation that used extra sufficiency conditions via amplitude equations (UGA-SSMRPT2 scheme A). (b) We present the results for a variety of electronic states of a set of molecules, which display the striking accuracy of both the two versions of UGA-SSMRPT2 with respect to three different situations involving weakly avoided crossings, moderate/strongly avoided crossings, and interlacing in a manifold of potential energy curves (PECs) of the same symmetry. Accuracy of our results has been benchmarked against IC-MRCISD + Q., ((c) For weakly avoided crossing between states displaying differently charged sectors around the crossing region, the insufficient inclusion of state-specific orbital relaxation and the absence of dynamic correlation induced by orbital relaxation in the first order wavefunction for a second order perturbative theory lead to an artifact of double crossing between the pair of PECs.)

Body mass index (BMI) is a main indicator of obesity and its association with breast cancer is well established. However, little is known in the metastatic setting, especially in HER2-positive patients. We assessed the influence of BMI on clinical outcomes of patients treated with pertuzumab and/or trastuzumab emtansine (T-DM1) for HER2+ metastatic breast cancer (mBC). BMI was addressed as a categorical variable, being classified on the basis of the following ranges, that is, 18.5-24.9, 25-29.9, and 30.0-34.9, namely, normal weight, overweight, and Class I obesity. The outcomes chosen were progression-free survival to first-line chemotherapy (PFS1) and overall survival (OS). Overall (N = 709), no impact of BMI was observed on PFS1 (p = .15), while BMI ≥ 30 was associated with worse OS (p = .003). In subjects who progressed to first line (N = 575), analyzing data across PFS1 quartiles and strata of disease burden, BMI predicted lower PFS1 in patients within the I PFS1 quartile and with the lowest disease burden (p = .001). Univariate analysis showed a detrimental effect of BMI ≥ 30 on OS for women within the I PFS1 quartile (p = .03). Results were confirmed in multivariate analysis. According to PFS1 quartiles a higher percentage of patients with high BMI and low disease burden progressed within 6 months of therapy. The effect of BMI on prognosis was also confirmed in multivariate analysis of OS for overall population. In our cohort, a BMI ≥ 30 correlated with worse OS in patients with HER2+ mBC who received pertuzumab and/or T-DM1 but had no impact on PFS to first line. BMI predicted worse I PFS1 quartile., (© 2020 Wiley Periodicals, Inc.)

A hypercoagulable state may either underlie or frankly accompany cancer disease at its onset or emerge in course of cancer development. Whichever the case, hypercoagulation may severely limit administration of cancer therapies, impose integrative supporting treatments and finally have an impact on prognosis. Within a flourishing research pipeline, a recent study of stage I-IIA breast cancer patients has allowed the development of a prognostic model including biomarkers of coagulation activation, which efficiently stratified prognosis of patients in the study cohort. We are now validating our risk assessment tool in an independent cohort of 108 patients with locally advanced breast cancer with indication to neo-adjuvant therapy followed by breast surgery. Within this study population, we will use our tool for risk assessment and stratification in reference to 1. pathologic complete response rate at definitive surgery, intended as our primary endpoint, and 2. rate of thromboembolic events, intended as our secondary endpoint. Patients' screening and enrollment procedures are currently in place. The trial will be shortly enriched by experimental tasks centered on next-generation sequencing techniques for identifying additional molecular targets of treatments which may integrate current standards of therapy in high-risk patients.

Background: The occurrence of periodontitis is rather infrequent in children and adolescence and increases with age. We conducted this study because there have been few epidemiological studies on prevalence of periodontitis in children in Saudi Arabia., Objective: Determine the prevalence of periodontitis in high school children in Saudi Arabia., Design: Cross-sectional, using cluster and multistage sampling., Setting: High school children in Saudi Arabia., Participants and Methods: Periodontal examinations were conducted on a randomized sample of high school children between the ages 15 to 19 in Saudi Arabia. The study spanned from September 2012 to January 2016. Clinical examinations included measurements of the probing depth (PD) percentage of PD ≥4 mm per patient., Main Outcome Measures: The prevalence of periodontitis (PD ≥4 mm and CAL ≥1 mm), the mean percentage PD ≥4 mm, the mean percentage CAL ≥1 mm, plaque index (PI) and gingival index (GI)., Sample Size: 2435 high school students., Results: Of 2435 high school children in the sample, 209 students (8.6%) had periodontitis. The mean (standard deviation) for the PD was 0.59 (0.17) mm. Differences in percentage PD ≥4 mm and CAL ≥1 mm were greater in students with periodontitis ( P<.001). The prevalence of periodontitis was higher among non-Saudis, students who did not brush their teeth and did not visit their dentist regularly. In the bivariate analysis, periodontitis was positively associated with GI, PI, number of teeth extracted, mean percentage PD ≥4 mm, and mean PD. However, in the multivariate analysis, tooth brushing was the main factor protective against periodontitis (odds ratio: 0.62, 95% CI 0.42-0.92, P=.017)., Conclusion: Periodontitis prevalence was high compared with Western countries in a nationally representative sample of high school students in Saudi Arabia., Limitations: Partial mouth study design, which may underestimate the disease prevalence., Conflict of Interest: None.

Triple negative breast cancer (TNBC) is characterized by distinctive biological features that confer an aggressive clinical behavior. In TNBC patients, the absence of well-defined driver pathways such as hormonal receptor expression or hyperactivation of the human epidermal growth factor receptor 2 (HER2) significantly reduce the spectrum of therapeutic options, which are currently mainly confined to chemotherapy. Thus far, median overall survival for patients with metastatic TNBC is about 9-12 months with conventional cytotoxic agents. However, the heterogeneity recently revealed at a gene expression level inside the TNBC family may help inform therapeutic decisions concerning the use of chemotherapy and hopefully lead the way to novel targeted options that include immunotherapy. Eribulin, a halichondrin class antineoplastic drug, is currently recommended for treatment of HER2 negative metastatic or recurrent breast cancer (BC) previously exposed to anthracyclines and taxanes, also for patients with a TNBC. It is currently indicated from the second line of treatment. In this review, we aim to analyze a wide range of cumulated evidence on eribulin use in TNBC including preclinical studies, intervention and observational clinical trials. Data from the real-world setting and the emerging evidence increasingly substantiating the rationale for combinations with new generation treatment strategies, e.g., PARP-inhibitors, immune checkpoint inhibitors, will be also discussed., Competing Interests: Competing Interests: EK, GB, MM, MB, AA, GM, FP, RK, EV, AG, ST, AV, PM, GS, GC declare no conflicts of interest. LP received travel grants from Eisai, Roche, Pfizer, Novartis; speaker fees from Roche, Pfizer, Novartis, Gentili. TG received travel grants from Eisai, Roche, Pfizer, Novartis; speaker fees/advisory boards from Roche, Pfizer, Novartis, Gentili, Lilly. CN received travel grants/personal fees from Pfizer, EISAI, Novartis, Merck Sharp & Dohme, AstraZeneca. PV received travel grants from Eisai, Roche, Pfizer, Novartis; speaker fees/advisory boards from Roche, Pfizer, Novartis, Gentili., (© The author(s).)

Data from 423 human epidermal growth factor receptor 2-negative (HER2-), hormone receptor-positive (HR+) advanced breast cancer (aBC) patients treated with palbociclib and endocrine therapy (ET) were provided by 35 Italian cancer centers and analyzed for treatment outcomes. Overall, 158 patients were treated in first line and 265 in second/later lines. We observed 19 complete responses and 112 partial responses. The overall response rate (ORR) was 31% (95% confidence interval [CI], 26.6-35.4) and clinical benefit was 52.7% (95% CI, 48-57.5). ORR was negatively affected by prior exposure to everolimus/exemestane ( p = 0.002) and favorably influenced by early line-treatment ( p < 0.0001). At 6 months, median progression-free survival was 12 months (95% CI, 8-16) and median overall survival was 24 months (95% CI, 17-30). More favorable outcomes were associated with palbociclib in early lines, no visceral metastases and no prior everolimus/exemestane. The main toxicity reported was neutropenia. Our results provide further support to the use of palbociclib with ET in HER2-, HR+ aBC. Differences in outcomes across patients subsets remain largely unexplained., (© 2018 Wiley Periodicals, Inc.)

Purpose: To retrospectively evaluate the value of whole-lesion histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating between lymphoma and metastatic squamous cell carcinoma (SCC) of unknown clinical primary in neck nodes., Methods: A total of 39 patients, 20 affected by lymphoma and 19 affected by metastatic non-nasopharyngeal SCC, were included in this retrospective study. All patients underwent MR imaging with a 1.5 T scanner system, including diffusion-weighted imaging (DWI) with three different b values (b = 0, 500 and 800 s/mm 2 ). The entire tumor volume was manually delineated on the ADC maps, using the T2-weighted images and DWIs with b = 800 s/mm 2 as a guide to the lesion location. The Mann-Whitney rank-sum test for independent samples was performed to compare the histogram parameters of patients with lymphoma and SCC., Results: The SCCs showed significantly higher median ADC (ADC median ) and mean ADC (ADC mean ) values, compared to lymphomas (p < 0.001), while they exhibited lower kurtosis and skewness without reaching significance (p = 0.066 and 0.148, respectively). The ADC mean and ADC median had the best discriminative powers for differentiating lymphoma and SCC, with an area under the curve of 87% and 85%, respectively. The optimal cutoff values for ADC mean and ADC median as predictors for lymphoma were ≤ 0.83 × 10 -3 mm 2 /s and ≤ 0.73 × 10 -3 mm 2 /s, respectively., Conclusions: The whole-lesion ADC histogram analysis of cervical lymphadenopathy may help to discriminate lymphomas from non-nasopharyngeal SCC in patients with unknown clinical primary tumor.

Among several virulence factors produced by the periodontal pathogen Porphyromonas gingivalis (Pg), a recently identified novel class of dihydroceramide lipids that contains a long acyl-chain has the potential to play a pathogenic role in periodontitis because of its higher level of tissue penetration compared to other lipid classes produced by Pg. However, the possible impact of Pg ceramides on osteoclastogenesis is largely unknown. In the present study, we report that the phosphoglycerol dihydroceramide (PGDHC) isolated from Pg enhanced osteoclastogenesis in vitro and in vivo. Using RAW264.7 cells, in vitro assays indicated that PGDHC can promote RANKL-induced osteoclastogenesis by generating remarkably larger TRAP+ multinuclear osteoclasts compared to Pg LPS in a TLR2/4-independent manner. According to fluorescent confocal microscopy, co-localization of non-muscle myosin II-A (Myh9) and PGDHC was observed in the cytoplasm of osteoclasts, indicating the membrane-permeability of PGDHC. Loss- and gain-of-function assays using RNAi-based Myh9 gene silencing, as well as overexpression of the Myh9 gene, in RAW264.7 cells showed that interaction of PGDHC with Myh9 enhances RANKL-induced osteoclastogenesis. It was also demonstrated that PGDHC can upregulate the expression of dendritic cell-specific transmembrane protein (DC-STAMP), an important osteoclast fusogen, through signaling that involves Rac1, suggesting that interaction of PGDHC with Myh9 can elicit the cell signal that promotes osteoclast cell fusion. Taken together, our data indicated that PGDHC is a Pg-derived, cell-permeable ceramide that possesses a unique property of promoting osteoclastogenesis via interaction with Myh9 which, in turn, activates a Rac1/DC-STAMP pathway for upregulation of osteoclast cell fusion., (Copyright © 2017. Published by Elsevier B.V.)

Using a mouse model of silk ligature-induced periodontal disease (PD), we report a novel method of sampling mouse gingival crevicular fluid (GCF) to evaluate the time-dependent secretion patterns of bone resorption-related cytokines. GCF is a serum transudate containing host-derived biomarkers which can represent cellular response in the periodontium. As such, human clinical evaluations of PD status rely on sampling this critical secretion. At the same time, a method of sampling GCF from mice is absent, hindering the translational value of mouse models of PD. Therefore, we herein report a novel method of sampling GCF from a mouse model of periodontitis, involving a series of easy steps. First, the original ligature used for induction of PD was removed, and a fresh ligature for sampling GCF was placed in the gingival crevice for 10min. Immediately afterwards, the volume of GCF collected in the sampling ligature was measured using a high precision weighing balance. The sampling ligature containing GCF was then immersed in a solution of PBS-Tween 20 and subjected to ELISA. This enabled us to monitor the volume of GCF and detect time-dependent changes in the expression of such cytokines as IL-1b, TNF-α, IL-6, RANKL, and OPG associated with the levels of alveolar bone loss, as reflected in GCF collected from a mouse model of PD. Therefore, this novel GCF sampling method can be used to measure various cytokines in GCF relative to the dynamic changes in periodontal bone loss induced in a mouse model of PD., (Copyright © 2016. Published by Elsevier B.V.)

Osteoclastogenesis was induced by RANKL stimulation in mouse monocytes to examine the possible bactericidal function of osteoclast precursors (OCp) and mature osteoclasts (OCm) relative to their production of NO and ROS. Tartrate-resistant acid phosphatase (TRAP)-positive OCp, but few or no OCm, phagocytized and killed Escherichia coli in association with the production of reactive oxygen species (ROS) and nitric oxide (NO). Phagocytosis of E. coli and production of ROS and NO were significantly lower in TRAP+ OCp derived from Toll-like receptor (TLR)-4 KO mice than that derived from wild-type (WT) or TLR2-KO mice. Interestingly, after phagocytosis, TRAP+ OCp derived from wild-type and TLR2-KO mice did not differentiate into OCm, even with continuous exposure to RANKL. In contrast, E. coli-phagocytized TRAP+ OCp from TLR4-KO mice could differentiate into OCm. Importantly, neither NO nor ROS produced by TRAP+ OCp appeared to be engaged in phagocytosis-induced suppression of osteoclastogenesis. These results suggested that TLR4 signaling not only induces ROS and NO production to kill phagocytized bacteria, but also interrupts OCm differentiation. Thus, it can be concluded that TRAP+ OCp, but not OCm, can mediate bactericidal activity via phagocytosis accompanied by the production of ROS and NO via TLR4-associated reprograming toward phagocytic cell type., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Over the last twenty years, the efforts of the scientific community devoted to the comprehension and treatment of ovarian cancer have remained poorly remunerative, with the case-fatality ratio of this disease remaining disappointedly high. Limited knowledge of the basic principles regulating ovarian carcinogenesis and factors impacting the course of disease may significantly impair our ability to intervene in early stages and lessen our expectations in terms of treatment outcomes. In the present study, we sought to assess whether metabolic factors and anthropometric indicators, i.e., pre-treatment fasting glucose and body mass index, are associated with renown cancer related prognostic factors such as tumour stage and grade at diagnosis., Materials and Methods: Study participants were 147 women diagnosed with epithelial ovarian cancer and treated with platinum based regimens and/or surgery at the Regina Elena National Cancer Institute of Rome, Italy. Glucose levels were assessed at the institutional laboratories on venous blood collected in overnight fasting conditions and prior to any therapeutic procedure. Stage was coded according to the FIGO staging system based on the results of the diagnostic workup, while tumour grade was locally assessed by an expert pathologist. Participants' characteristics were descriptively analyzed for the overall study population and in a subgroup of 70 patients for whom data on body mass index (BMI) were available. FIGO stage and grade were compared by categories of pre-treatment fasting glucose defined upon the median value, i.e., 89 mg/dl. The association of interest was tested in regression models including BMI., Results: For the overall study population, patients in the lowest category of fasting glucose were significantly more likely to exhibit a FIGO stage III-IV at diagnosis compared with their counterpart in the highest glucose category (81.3 vs 66.7%, p: 0.021). Subgroup analysis in 70 patients with BMI data confirmed this association (81.5 vs 55.8, p: 0.049), which remained significant when tested in regression models including BMI (OR: 0.28 95% CI 0.086-0.89, p: 0.031). No relevant evidence emerged when testing the association between fasting glucose and tumour grade., Conclusions: In patients diagnosed with epithelial ovarian cancer, pre-treatment glucose levels appear to be inversely associated with FIGO stage. Further studies are warranted to eventually confirm and correctly interpret the implications of this novel finding.

Background: In this retrospective study, we investigated the efficacy and safety of radioimmunotherapy with (90)Yttrium- ibritumomab tiuxetan ((90)Y-RIT) in 9 patients with recurrent follicular lymphoma (FL) who were treated in a consolidation setting after having achieved complete (CR) or partial remission (PR) with Fludarabine, Cyclophosphamide and Rituximab (FCR)., Methods: The median age was 63 years (range 46-77). All patients were relapsed with histologically confirmed CD20-positive (grade 1 or 2) FL, at relapse they received FCR every 28 days: F (25 mg/m(2)x 3 days), C (1 gr/m(2) day 1) and R (375 mg/m(2) day 4) for 4 cycles. Those who achieved at least a PR with <25 % bone marrow involvement were treated with (90)Y-RIT 11.1 or 14.8 MBq/Kg, at 3 months after completing FCR. Patients underwent a further restaging at 12 weeks after (90)Y-RIT with a total body CT scan, FDG-PET/CT and bilateral bone marrow biopsy., Results: Nine patients completed the treatment: FCR followed by (90)Y-RIT (6 patients at 14.8 MBq/Kg, 3 patients at 11.1 MBq/Kg). After FCR, 7 patients obtained CR and 2 PR; after (90)Y-RIT 2 patients in PR converted to CR 12 weeks later. With a median follow up of 95 months (range 20-114) since FCR and 88 months (range 13-104) since (90)Y-RIT 3 deaths were not related to lymphoma; all 3 deceased patients obtained CR before (90)Y-RIT and died still in CR. The median overall (OS) and progression free survival (PFS) have not been reached, in this analysis both OS or PFS are 67 % at 7.5 year. The most common grade 3 or 4 adverse events were hematologic., Conclusions: These results confirm the long term efficacy and safety of 4 cycles of FCR followed by (90)Y-RIT in relapsed grades 1 and 2 FL and suggest that this regimen could be a therapeutic option for this setting of patients, specially at age of 60-75 with no unexpected toxicities.

Objective: To investigate the ability of neck ultrasounds (US), magnetic resonance imaging (MRI) and positron emission tomography (FDG-PET/TC) in detecting residual nodal disease after chemoradiotherapy in patients with advanced oropharyngeal squamous cell carcinoma (OPSCC)., Methods: From 2006 to 2009, 36 consecutive patients affected by OPSCC with bulky nodal disease (>3 cm), treated with primary concurrent chemoradiotherapy, were enrolled prospectively. Nodal response to treatment was assessed by using US, MRI and FDG-PET/CT. Planned neck dissection (ND) was performed in all the patients, and the histopathological node status was compared to the imaging findings in order to establish sensitivity, specificity, accuracy and predictive values of each technique., Results: Metastatic disease was assessed in 18/37 (48.6%) hemi-necks, always localized in levels II-IV. US showed greater sensitivity (77.8%) and, combined with FDG-PET/TC, produced the highest negative predictive value (93.3%). US, MRI and FDG-PET/TC scans showed the highest specificity (100%), accuracy (93.8%) and positive predictive values (100%)., Conclusions: In the presence of advanced OPSCC with bulky nodal disease, US combined with FDG-PET/TC could be a reliable and cost-effective strategy to identify patients with complete nodal response to chemoradiotherapy that might not require post-treatment ND but only observation. When residual disease in the neck was detected, selective ND was recommended., (Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

We report a case of deep peroneal neuropathy resulting in foot drop with preserved toe extension. These unexpected findings were the result of the presence of an accessory deep peroneal nerve that provided total innervation of the extensor digitorum brevis. We review the literature on total innervation of the extensor digitorum brevis by the accessory deep peroneal nerve with and without an associated deep peroneal nerve lesion. Muscle Nerve 40: 313-315, 2009.

Rat and mouse femur and tibia fracture calluses were collected over various time increments of healing. Serial sections were produced at spatial segments across the fracture callus. Standard histological methods and in situ hybridization to col1a1 and col2a1 mRNAs were used to define areas of cartilage and bone formation as well as tissue areas undergoing remodeling. Computer-assisted reconstructions of histological sections were used to generate three-dimensional images of the spatial morphogenesis of the fracture calluses. Endochondral bone formation occurred in an asymmetrical manner in both the femur and tibia, with cartilage tissues seen primarily proximal or distal to the fractures in the respective calluses of these bones. Remodeling of the calcified cartilage proceeded from the edges of the callus inward toward the fracture producing an inner-supporting trabecular structure over which a thin outer cortical shell forms. These data suggest that the specific developmental mechanisms that control the asymmetrical pattern of endochondral bone formation in fracture healing recapitulated the original asymmetry of development of a given bone because femur and tibia grow predominantly from their respective distal and proximal physis. These data further show that remodeling of the calcified cartilage produces a trabecular bone structure unique to fracture healing that provides the rapid regain in weight-bearing capacity to the injured bone.

This study investigated the accuracy of phase contrast MRI in blood flow measurements; both in vitro and in vivo studies were carried out. Five normal volunteers (3 women and 2 men, age range: 24 to 30 years) were examined with MR angiography (MRA) and a flow measurement sequence. A 2D phase contrast sequence, with retrospective cardiac gating was also acquired with the following imaging parameters: TR/TE/FA (26/9.3/20 degrees ), field of view 150 mm, matrix 96 x 128; 4 averages. VENC value (cm/s) was chosen according to the examined region. The total acquisition time ranged 3 min 25 sec to 4 min 38 sec. The sequences were acquired on a plane perpendicular to the vessel direction, using MIP-reconstructed MRA images as a scout view. The results are the same as those obtained with other techniques, in the common carotid artery (Vmax = 70.7 cm/s; Vmin = 18.8 cm/sec; flow = 348 ml/min), internal carotid artery (Vmax -54.4 cm/sec; Vmin = 18 cm/sec; flow = 236 ml/min) and vertebral artery (Vmax = 51.7 cm/sec; Vmin = 17.5 cm/sec). The resistance index could always be calculated and exceeded 0.7 in all cases. In conclusion, MRA is an accurate technique for blood flow measurements, in particular with cardiac gating, which permits measurement optimization according to the different cardiac cycles.

Color Doppler gives us the possibility to study autonomous thyroid nodules and their qualitative and morphological aspects and allows us to hit session by session the most vascular area of the nodule with alcohol (Percutaneous ethanol injection). The use of color gives an easier flowmeter analysis reducing its time of performance. Today this method with the latest up to date echographs can provide very good clinical pathology at relatively low costs. We studied 18 patients, with autonomous thyroid nodules. They were all treated by percutaneous echo-guided ethanol injection (PEI). Before the beginning we make sure that the rest of the thyroid gland may function normally. The color Doppler test was carried out by using the multidisciplinary ecotomograph AU 560 CFM supplied with a linear probe 7.5 mHz, AL 35 by Esaote Biomedica. Before the PEI treatment, with the eco color Doppler test we noticed that the hot nodules clearly presented a higher vascularization compared to the remaining parenchyma. The vascularization was more evident in the peripheral area of the nodule even if few signs of flow were present inside the nodule. During a 24 months followup, 10 patients showed an important reduction and sometimes even the extinction of the intranodular flow signs followed by a clear reduction of the nodule's volume.