Treatment of simple bone cyst with bone marrow concentrate and equine-derived demineralized bone matrix injection versus methylprednisolone acetate injections: A retrospective comparative study

Objective: The aim of this study was to compare the outcome of intra-lesional autologous bone marrow concentrate (BMC) and equine derived demineralized bone matrix (EDDBM) injections with methylprednisolone acetate injections in patients with simple bone cyst. Methods: Clinical records and radiographs of 53 consecutive patients (37 females, and 16 males; mean age: 10.61 +/- 1.53 years) treated between 2006 and 2016 were retrospectively reviewed. Healing was assessed by an independent radiologist according to Neer scoring system. Functional outcome was assessed with the Activity Scale for Kids (ASK). Thirty-four cysts were in the humerus, 13 in the femur and 6 in other locations. Twenty-nine patients were included in Steroid Group and treated with 3 cycles of injections of methylprednisolone acetate, while 24 patients were treated with injection of autologous bone marrow concentrate and equine derived demineralized bone matrix (BMC + EDDBM Group). The two groups were homogenous for the mean age, sex distribution, cysts location and their clinical presentation. Results: At a minimum follow-up of 24 months, success rate (Neer/Cole score 3 and 4) was higher in EDDBM+BMC group (83.3% vs 58.6%; p=0.047). Female patients had higher healing rates in both groups (p=0.002). No association was found between healing and age (p=0.839), cyst activity (p=0.599), cyst localization (p=0.099) and clinical presentation (p=0.207). BMC+EDDBM group showed higher ASK score (p=0.0007). Conclusion: Treatment with BMC+EDDBM injections may provide better results with a single procedure than 3 methylprednisolone acetate injections and represent an interesting alternative for the treatment of unicameral bone cysts

Resonant micro-opto-mechanical modulators fabricated by femtosecond laser micromachining

Integrated modulators of optical phase or intensity are essential elements to reconfigure dynamically the operation of a complex waveguide circuit, or to achieve convenient optical switching within a fiber network. Thermo-optic effects are commonly exploited to achieve dynamic phase modulation in glass-based devices, since nonlinear optical effects are weak in such substrates. Thermo-optic modulators rely on electric resistive heaters patterned on top of the waveguides: they are reliable and easy to fabricate, but they suffer from slow response, dictated by the thermal diffusion dynamics. On the other hand, optically-coupled microstructures in glass, driven at their mechanical resonances, may provide interesting possibilities to achieve modulation of the optical signals in the kilohertz range and higher. In this work, we demonstrate integrated-optics intensity modulators based on micro-cantilevers with resonant oscillation frequencies in the tens-of-kilohertz range. The mechanical structures are realized in alumino-borosilicate glass substrate by water-assisted femtosecond-laser ablation. With the same femtosecond laser an optical waveguide is inscribed within the oscillating beam; a waveguide also continues in the substrate beyond the cantilever's tip. Since the entire device, with all its optical and mechanical parts, is realized in a single fabrication process, relative alignment is guaranteed. If the cantilever is at rest, light propagating in the internal waveguide yields maximum coupling to the remaining part of the waveguide. When the device is excited at resonance by means of a piezo-electric actuator, the cantilever oscillation produces periodical variations of the coupling efficiency, with an observed contrast higher than 10 dB

Three-dimensional and dual-color fluorescence microscopy on a chip

In this work we present two microscopes on chip based on Light Sheet Fluorescence Microscopy, capable to automatically perform 3D and dual-color imaging of specimens diluted in a liquid suspension. A microfluidic channel is used for automatic sample delivery, while integrated optical components such as optical waveguides and lenses are used to illuminate the sample flowing in the channel. The devices are fabricated by femtosecond laser micromachining in a glass substrate. Benefiting from the versatility of the fabrication technique we present two prototypes that have been optimized for different samples such as single cells and Drosophila embryos

Role of BRAF in Hepatocellular Carcinoma: A Rationale for Future Targeted Cancer Therapies

The few therapeutic strategies for advance hepatocellular carcinoma (HCC) on poor knowledge of its biology. For several years, sorafenib, a tyrosine kinase inhibitors (TKI) inhibitor, has been the approved treatment option, to date, for advanced HCC patients. Its activity is the inhibition of the retrovirus-associated DNA sequences protein (RAS)/Rapidly Accelerated Fibrosarcoma protein (RAF)/mitogen-activated and extracellular-signal regulated kinase (MEK)/extracellular-signal regulated kinases (ERK) signaling pathway. However, the efficacy of sorafenib is limited by the development of drug resistance, and the major neuronal isoform of RAF, BRAF and MEK pathways play a critical and central role in HCC escape from TKIs activity. Advanced HCC patients with a BRAF mutation display a multifocal and/or more aggressive behavior with resistance to TKI. Moreover, also long non-coding RNA (lnc-RNA) have been studied in epigenetic studies for BRAF aggressiveness in HCC. So far, lnc-RNA of BRAF could be another mechanism of cancer proliferation and TKI escape in HCC and the inhibition could become a possible strategy treatment for HCC. Moreover, recent preclinical studies and clinical trials evidence that combined treatments, involving alternative pathways, have an important role of therapy for HCC and they could bypass resistance to the following TKIs: MEK, ERKs/ribosomal protein S6 kinase 2 (RSK2), and phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR). These initial data must be confirmed in clinical studies, which are currently ongoing. Translational research discoveries could create new strategies of targeted therapy combinations, including BRAF pathway, and they could eventually bring light in new treatment of HCC

Cancer stem cell biomarkers predictive of radiotherapy response in rectal cancer: A systematic review

Background: Rectal cancer (RC) is one of the most commonly diagnosed and particularly challenging tumours to treat due to its location in the pelvis and close proximity to critical genitouri-nary organs. Radiotherapy (RT) is recognised as a key component of therapeutic strategy to treat RC, promoting the downsizing and downstaging of large RCs in neoadjuvant settings, although its therapeutic effect is limited due to radioresistance. Evidence from experimental and clinical studies indicates that the likelihood of achieving local tumour control by RT depends on the complete eradica-tion of cancer stem cells (CSC), a minority subset of tumour cells with stemness properties. Methods: A systematic literature review was conducted by querying two scientific databases (Pubmed and Scopus). The search was restricted to papers published from 2009 to 2021. Results: After assessing the quality and the risk of bias, a total of 11 studies were selected as they mainly focused on biomarkers predictive of RT-response in CSCs isolated from patients affected by RC. Specifically these studies showed that elevated levels of CD133, CD44, ALDH1, Lgr5 and G9a are associated with RT-resistance and poor prognosis. Conclusions: This review aimed to provide an overview of the current scenario of in vitro and in vivo studies evaluating the biomarkers predictive of RT-response in CSCs derived from RC patients

Anterior cruciate ligament recostruction with bone-patellar tendon-bone autograft in Tanner 3 stage patients with open physes

Ten skeletally immature patients were treated with an arthroscopic-assisted anterior cruciate ligament reconstruction with bone-patellar tendon bone autograft (compass, 50\u2013558; holes, 7\u20139 mm). Radiological assessments (standard radiograph), Orthopa\ua8 dische Arbeitsgruppe Knie (OAK) score and KT 1000, were conducted on all patients, 1 year after surgery. Skeletal maturity had been reached by all patients and no complications were observed. All patients returned to their preinjury sport level. Drilling more vertical tunnels when bone-tendon-bone autograft was chosen to avoid partial epiphysiodesis and offers good functional and isometric results

Lactate dehydrogenase in hepatocellular carcinoma: something old, something new

Hepatocellular carcinoma (HCC) is the most common primary liver tumour (80-90%) and represents more than 5.7% of all cancers. Although in recent years the therapeutic options for these patients have increased, clinical results are yet unsatisfactory and the prognosis remains dismal. Clinical or molecular criteria allowing a more accurate selection of patients are in fact largely lacking. Lactic dehydrogenase (LDH) is a glycolytic key enzyme in the conversion of pyruvate to lactate under anaerobic conditions. In preclinical models, upregulation of LDH has been suggested to ensure both an efficient anaerobic/glycolytic metabolism and a reduced dependence on oxygen under hypoxic conditions in tumour cells. Data from several analyses on different tumour types seem to suggest that LDH levels may be a significant prognostic factor. The role of LDH in HCC has been investigated by different authors in heterogeneous populations of patients. It has been tested as a potential biomarker in retrospective, small, and nonfocused studies in patients undergoing surgery, transarterial chemoembolization (TACE), and systemic therapy. In the major part of these studies, high LDH serum levels seem to predict a poorer outcome. We have reviewed literature in this setting trying to resume basis for future studies validating the role of LDH in this diseas

Characterization of Nonlinear Finger Pad Mechanics for Tactile Rendering

The computation of skin forces and deformations for tactile rendering requires an accurate model of the extremely nonlinear behavior of the skin. In this work, we investigate the characterization of finger mechanics with the goal of designing accurate nonlinear models for tactile rendering. First, we describe a measurement setup that enables the acquisition of contact force and contact area in the context of controlled finger indentation experiments. Second, we describe an optimization procedure that estimates the parameters of strain-limiting deformation models that match best the acquired data. We show that the acquisition setup allows the measurement of force and area information with high repeatability, and the estimation method reaches nonlinear models that match the measured data with high accuracy

Systematic review of irreversible electroporation role in management of locally advanced pancreatic cancer

Background: Ablative techniques provide in patients with locally advanced pancreatic cancer (LAPC) symptomatic relief, survival benefit and potential downsizing. Irreversible Electroporation (IRE) represents potentially an ideal solution as no thermal tissue damage occurs. The purpose of this review is to present an overview on safety, feasibility, oncological results, survival and quality of life improvement obtained by IRE. Methods: A systematic search was performed in PubMed, regarding the use of IRE on PC in humans for studies published in English up to March 2019. Results: 15 original studies embodying 691 patients with unresectable LAPC who underwent IRE were included. As emerged, IRE works better on tumour sizes between 3–4 cm. Oncological results are promising: median OS from diagnosis or treatment up to 27 months. Two groups investigated borderline resectable tumours treated with IRE before resection with margin attenuation, whereas IRE has proved to be effective in pain control. Conclusions: Electroporation is bringing new hopes in LAPC management. The first aim of IRE is to offer a palliative treatment. Further efforts are needed for patient selection, as well as the use of IRE for ‘margin accentuation’ during surgical resection. Even if promising, IRE needs to be validated in large, randomized, prospective series

Laparoscopic vs. open mesorectal excision for rectal cancer: Are these approaches still comparable? A systematic review and metaanalysis

Background To analyze pathologic and perioperative outcomes of laparoscopic vs. open resections for rectal cancer performed over the last 10 years. Methods A systematic literature search of the following databases was conducted: Cochrane Central Register of Controlled Trials, MEDLINE (through PubMed), EMBASE, and Scopus. Only articles published in English from January 1, 2008 to December 31, 2018 (i.e. the last 10 years), which met inclusion criteria were considered. The review only included articles which compared Laparoscopic rectal resection (LRR) and Open Rectal Resection (ORR) for rectal cancer and reported at least one of the outcomes of interest. The analyses followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement checklist. Only prospective randomized studies were considered. The body of evidence emerging from this study was evaluated using the Grading of Recommendations Assessment Development and Evaluation (GRADE) system. Outcome measures (mean and median values, standard deviations, and interquartile ranges) were extracted for each surgical treatment. Pooled estimates of the mean differences were calculated using random effects models to consider potential inter-study heterogeneity and to adopt a more conservative approach. The pooled effect was considered significant if p <0.05. Results Five clinical trials were found eligible for the analyses. A positive involvement of CRM was found in 49 LRRs (8.5%) out of 574 patients and in 30 ORRs out of 557 patients (5.4%) RR was 1.55 (95% CI, 0.99–2.41; p = 0.05) with no heterogeneity (I2 = 0%). Incorrect mesorectal excision was observed in 56 out of 507 (11%) patients who underwent LRR and in 41 (8.4%) out of 484 patients who underwent ORR; RR was 1.30 (95% CI, 0.89–1.91; p = 0.18) with no heterogeneity (I2 = 0%). Regarding other pathologic outcomes, no significant difference between LRR and ORR was observed in the number of lymph nodes harvested or concerning the distance to the distal margin. As expected, a significant difference was found in the operating time for ORR with a mean difference of 41.99 (95% CI, 24.18, 59.81; p <0.00001; heterogeneity: I2 = 25%). However, no difference was found for blood loss. Additionally, no significant differences were found in postoperative outcomes such as postoperative hospital stay and postoperative complications. The overall quality of the evidence was rated as high. Conclusion Despite the spread of laparoscopy with dedicated surgeons and the development of even more precise surgical tools and technologies, the pathological results of laparoscopic surgery are still comparable to those of open ones. Additionally, concerning the pathological data (and particularly CRM), open surgery guarantees better results as compared to laparoscopic surgery. These results must be a starting point for future evaluations which consider the association between ‘‘successful resection” and long-term oncologic outcomes. The introduction of other minimally invasive techniques for rectal cancer surgery, such as robotic resection or transanal TME (taTME), has revealed new scenarios and made open and even laparoscopic surgery obsolete