BACKGROUND:Various operative techniques are used for treating recurrent anterior shoulder instability, and good mid-term results have been reported. The purpose of this study was to compare shoulder ...stability after treatment with the 2 commonly performed procedures, the arthroscopic Bankart soft-tissue repair and the open coracoid transfer according to Latarjet.
METHODS:A comparative, retrospective case-cohort analysis of 360 patients (364 shoulders) who had primary repair for recurrent anterior shoulder instability between 1998 and 2007 was performed. The minimum duration of follow-up was 6 years. Reoperations, overt recurrent instability (defined as recurrent dislocation or subluxation), apprehension, the subjective shoulder value (SSV), sports participation, and overall satisfaction were recorded.
RESULTS:An open Latarjet procedure was performed in 93 shoulders, and an arthroscopic Bankart repair was done in 271 shoulders. Instability or apprehension persisted or recurred after 11% (10) of the 93 Latarjet procedures and after 41.7% (113) of the 271 arthroscopic Bankart procedures. Overt instability recurred after 3% of the Latarjet procedures and after 28.4% (77) of the Bankart procedures. In the Latarjet group, 3.2% of the patients were not satisfied with their result compared with 13.2% in the Bankart group (p = 0.007). Kaplan-Meier analysis of survivorship, with apprehension (p < 0.001), redislocation (p = 0.01), and operative revision (p < 0.001) as the end points, documented the substantial superiority of the Latarjet procedure and the decreasing effectiveness of the arthroscopic Bankart repair over time. Twenty percent of the first recurrences after arthroscopic Bankart occurred no earlier than 91 months postoperatively, as opposed to the rare recurrences after osseous reconstruction, which occurred in the early postoperative period, with only rare late failures.
CONCLUSIONS:In this retrospective cohort study, the arthroscopic Bankart procedure was inferior to the open Latarjet procedure for repair of recurrent anterior shoulder dislocation. The difference between the 2 procedures with respect to the quality of outcomes significantly increased with follow-up time.
LEVEL OF EVIDENCE:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Ovarian Cancer Immunotherapy: Turning up the Heat Ghisoni, Eleonora; Imbimbo, Martina; Zimmermann, Stefan ...
International journal of molecular sciences,
06/2019, Letnik:
20, Številka:
12
Journal Article
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Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies. Despite surgery and chemotherapy, 5-years survival rates have improved only modestly over the past few ...decades remaining at 45% for advanced stages. Therefore, novel therapies are urgently needed. The presence of tumor-infiltrating lymphocytes (TILs) in OC tumor microenvironment (TME) has already proved to be correlated with overall survival (OS), while immune evasion mechanisms are associated with poor prognosis. Although these data indicate that immunotherapy has a strong rationale in OC, single agent immune-checkpoints inhibitors (ICIs) have shown only modest results in this malignancy. In this review, we will discuss immune-targeting combination therapies and adoptive cell therapy (ACT), highlighting the challenges represented by these strategies, which aim at disrupting the stroma-tumor barrier to boost immune system against ovarian cancer.
Indole polycycles are common structural frameworks of biologically intriguing small molecules of natural and synthetic origin and therefore remain interesting and challenging synthetic targets. ...Cascade reactions wherein a number of reactions occur in a sequential manner in the same reaction apparatus are highly efficient chemical processes which quickly build up molecular complexity. Synthetic approaches based on cascade reactions are highly useful as they tend to avoid multiple reaction work-up steps as well as purifications of all intermediary products. Therefore, in the last decade, a number of cascade reaction based approaches to build various molecular scaffolds of biological interest have been reported. However, a relatively smaller number of cascade reaction based synthetic strategies have targeted the indole polycycles. In this article, we have summarized some interesting cascade reaction based synthesis designs leading to complex indole polycycles including some biologically intriguing and natural product inspired indole frameworks.
In this review, cascade reaction based synthesis strategies delivering biologically intriguing indole polycycles are presented.
Small-cell lung cancer (SCLC) is an aggressive disease with distinct pathological, clinical, and molecular characteristics from non-small-cell lung cancer. SCLC has high metastatic potential, ...resulting in a clinically poor prognosis. Early concurrent chemo-radiation is the standard of care for limited-stage SCLC (LS-SCLC). Prophylactic cranial irradiation (PCI) is recommended for patients with LS-SCLC without progression of disease after initial therapy. A combination of etoposide and cisplatin or carboplatin remains the mainstay of first-line treatment for ES-SCLC, with the addition of atezolizumab, now becoming standard. Most SCLCs initially respond to therapy but almost invariably recur. Topotecan and amrubicin (in Japan) remain the primary chemotherapy options for relapsed SCLC. Immunotherapy, including nivolumab with or without ipilimumab, is now available for refractory disease. In general, the poor prognosis of SCLC has not improved significantly for more than 3 decades. Recently, next-generation molecular profiling studies have identified new therapeutic targets for SCLC. A variety of proapoptotic agents, compounds capitalizing on DNA-repair defects, immunotherapy agents, and antibody-drug conjugates are being evaluated in SCLC, with a number of them showing early promise.
Technologies for Single-Cell Isolation Gross, Andre; Schoendube, Jonas; Zimmermann, Stefan ...
International journal of molecular sciences,
07/2015, Letnik:
16, Številka:
8
Journal Article
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The handling of single cells is of great importance in applications such as cell line development or single-cell analysis, e.g., for cancer research or for emerging diagnostic methods. This review ...provides an overview of technologies that are currently used or in development to isolate single cells for subsequent single-cell analysis. Data from a dedicated online market survey conducted to identify the most relevant technologies, presented here for the first time, shows that FACS (fluorescence activated cell sorting) respectively Flow cytometry (33% usage), laser microdissection (17%), manual cell picking (17%), random seeding/dilution (15%), and microfluidics/lab-on-a-chip devices (12%) are currently the most frequently used technologies. These most prominent technologies are described in detail and key performance factors are discussed. The survey data indicates a further increasing interest in single-cell isolation tools for the coming years. Additionally, a worldwide patent search was performed to screen for emerging technologies that might become relevant in the future. In total 179 patents were found, out of which 25 were evaluated by screening the title and abstract to be relevant to the field.
Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) was introduced into the microbiological routine more than 10 years ago. Since then it has almost replaced ...biochemical identification. It is unrivaled in terms of accuracy and cost. From a laboratory's perspective it would be an ideal method to replace classic susceptibility testing, that is Kirby-Baur agardiffusion or determination of minimal inhibitory concentrations (MICs). First reports on possible assays for susceptibility testing are more than 10 years old. However, the developments during the last 5 years were substantial. This review focuses with some exceptions on the progress, which was achieved during the last decade.
Scaffold diversity is a crucial feature of compound collections that has a huge impact on their success in biological screenings. The synthesis of highly complex and diverse scaffolds, which could be ...based on natural products, for example, is an arduous task that requires expertise in various aspects of organic synthesis and structural analysis. This challenge has been addressed by a number of synthesis designs, which employ natural products as a source of scaffold diversity, transform suitably designed common intermediates into various molecular frameworks, or entail highly concise synthetic routes to a number of distinct and complex scaffolds. In this Minireview, we highlight recent synthetic developments towards the construction of diverse and complex scaffolds and the application of the resulting compound collections in drug and probe discovery.
Complexity and diversity: The synthesis of compound libraries with a high degree of scaffold diversity has been addressed by transforming suitable common intermediates into various molecular frameworks or by using natural products as a source of scaffold diversity. In this Minireview, recent developments towards the construction of such libraries and their application in drug and probe discovery are summarized.
Abstract Lung cancer is characterized by the highest incidence of solid tumor-related brain metastases, which are reported with a growing incidence during the last decade. Prognostic assessment may ...help to identify subgroups of patients that could benefit from more aggressive therapy of metastatic disease, in particular when central nervous system is involved. The recent sub-classification of non-small cell lung cancer (NSCLC) into molecularly-defined “oncogene-addicted” tumors, the emergence of effective targeted treatments in molecularly defined patient subsets, global improvement of advanced NSCLC survival as well as the availability of refined new radiotherapy techniques are likely to impact on outcomes of patients with brain dissemination. The present review focuses on key evidence and research strategies for systemic treatment of patients with central nervous system involvement in non-small cell lung cancer.
Since its first proposal, the concept of on- and off-track lesions in anterior shoulder instability has gained clinical relevance as a tool to predict the failure rate of arthroscopic Bankart repair. ...Current literature only reports either short-term follow-up or long-term results of small sample sizes. The aim of this study was to provide a long-term evaluation of recurrent instability following arthroscopic Bankart repair in a large cohort using the on-track vs. off-track concept as a predictor for failure.
We retrospectively analyzed 271 patients who underwent primary arthroscopic Bankart repair for anterior shoulder instability between 1998 and 2007. All patients with a minimum follow-up of 78 months and a preoperative computed tomographic (CT) or magnetic resonance imaging (MRI) scan were included into the study. Preoperative CT and/or MRI scans were used to determine the glenoid track and width of Hill-Sachs lesion. Recurrence of instability was defined as presence of instability symptoms (dislocation, subluxation, and/or apprehension) or revision surgery (stabilization procedure) and was assessed as the primary outcome parameter.
The glenoid track of 163 shoulders was assessed (female n = 51, male n = 112) with a mean follow-up of 124 months (99.4-145.6, standard deviation = 2.5) and a mean age of 24 years (20-34.). An off-track Hill-Sachs lesion was found in 77 cases (47%), and in 86 cases (53 %) it was on-track. The rate of recurrent instability in the off-track group was 74% (n = 57) compared with 27% (n = 23) in the on-track group (P < .001). The overall rate of revision surgery due to instability was 29% (n = 48) after a mean time of 50.9 months (±42.8) following Bankart repair. The rate of revision surgery in the off-track group was 48% (n = 37) after a mean of 53.5 months (±42.0) vs. 13% (n = 11) after 42.3 months (±46.3) in the on-track group (P < .001).
This study shows that the on- and off-track concept helps to distinguish patients for whom an isolated arthroscopic Bankart repair yields long-term benefits. Because of the high rate of recurrent instability in the off-track group, an off-track lesion should be treated surgically in such a way that the off-track lesion is converted into an on-track lesion.
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