scholarly journals Uncoated vs. Antibiotic-Coated Tibia Nail in Open Diaphyseal Tibial Fracture (42 according to AO Classification): A Single Center Experience

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Tommaso Greco ◽  
Luigi Cianni ◽  
Chiara Polichetti ◽  
Michele Inverso ◽  
Giulio Maccauro ◽  
...  
Keyword(s):  
Reoperation Rate ◽  
Fracture Site ◽  
Categorical Variables ◽  
Type I ◽  
Single Center Experience ◽  
Fracture Stabilization ◽  
Deep Wound ◽  
Tibia Fractures ◽  
Group 3

Implant-associated infections remain one of the main problems in the treatment of open tibia fractures. The role of systemic antibiotic prophylaxis is now agreed and accepted; nevertheless, recent literature also seems to emphasize the importance of local antibiotic therapy at the fracture site. Several therapeutic strategies have been proposed to overcome this new need. Antibiotic-coated nails play crucial role in this, allowing both infection prevention and favoring the fracture stabilization. We describe the outcome of patients with open diaphyseal tibia fracture treated either with a standard uncoated nail or a gentamicin-coated nail from January 2016 to December 2018 at our second level emergency-urgency department. Primary outcomes were infection rate and bone union rate. Other outcomes reported are reoperation rate, time between injury and nailing, and safety of antibiotic nail. Numerical variables were tabulated using mean, standard deviation, minimum, maximum, and number of observations. Categorical variables were tabulated using number of observations. 23 patients treated with uncoated nail and 23 patients treated with antibiotic-coated tibia nail were included in the study and were evaluated for a minimum follow-up of 18 months. Among the 46 patients, 9 were Gustilo-Anderson type I, 21 type II, and 16 type III open fracture. Regarding the bone healing rate at 12 months, 16 fractures in the first group and 18 in the second were completely healed. 4 infections were found in the first group (3 superficial surgical site infection and 1 osteomyelitis) and 3 superficial infections in the second one. No adverse events have been recorded with antibiotic-coated nails. In this unicentric retrospective study observed no deep wound infections and good fracture healing in the use of antibiotic-coated nails. Antibiotic nails have been shown to play a role in the treatment of fractures in critically ill patients with severe soft tissue damage.

Adjunctive Procedures for the Treatment of Proximal Type I Endoleak: The Role of Peri-Aortic Ligatures and Palmaz Stenting

2003 ◽  
Vol 10 (2) ◽  
pp. 233-239 ◽  
Author(s):  
Elias Tzortzis ◽  
Robert J. Hinchliffe ◽  
Brian R. Hopkinson
Keyword(s):  
Endovascular Repair ◽  
Type I ◽  
Long Term Effects ◽  
Single Center Experience ◽  
Abdominal Aortic ◽  
Type I Endoleak ◽  
Secondary Procedures ◽  
Invasive Techniques

Purpose: To investigate the feasibility, efficacy, and long-term effects of peri-aortic ligatures and Palmaz stenting used to treat proximal type I endoleak after endovascular repair (EVR) of abdominal aortic aneurysm (AAA). Methods: An 8-year single-center experience with proximal type I endoleak was reviewed; the records of the 55 identified cases were examined to ascertain the methods of treatment used. Among these, all 22 patients who were treated with peri-aortic ligatures and Palmaz stenting were segregated for analysis. Results: The 22 patients (14 men; mean age 74.6 years, range 66–85) with proximal type I endoleak (18 early, 4 late) selected for analysis underwent 23 secondary procedures: 15 involving peri-aortic ligatures and 8 Palmaz stent implantations. Of the 18 early endoleaks, 11 were treated intraoperatively and 7 were observed. Ten (45%) patients died within 30 days of endoleak treatment: 8 had early endoleaks. Five of the 10 deaths occurred in patients successfully treated with peri-aortic ligatures (3/10) or Palmaz stenting (2/7). The 12 (54%) surviving patients suffered no aneurysm-related deaths or secondary endoleaks over a median follow-up of 20 months (range 4–75) Conclusions: Endoleak is an important mode of failure after endovascular repair. Peri-aortic ligatures and Palmaz stenting are feasible techniques for the treatment of proximal endoleak; however, the perioperative mortality of peri-aortic ligatures was higher when compared with other less invasive techniques. In contrast to other therapeutic options, these methods are more effective in the short and medium term.

Isoform-Selective PI3K Inhibitors for Various Diseases

2020 ◽  
Vol 20 (12) ◽  
pp. 1074-1092 ◽  
Author(s):  
Rammohan R.Y. Bheemanaboina
Keyword(s):  
Intracellular Signaling ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Type I ◽  
Selective Inhibitors ◽  
Pi3k Inhibitors ◽  
Wide Range ◽  
Lipid Kinases ◽  
Isoform Selectivity

Phosphoinositide 3-kinases (PI3Ks) are a family of ubiquitously distributed lipid kinases that control a wide variety of intracellular signaling pathways. Over the years, PI3K has emerged as an attractive target for the development of novel pharmaceuticals to treat cancer and various other diseases. In the last five years, four of the PI3K inhibitors viz. Idelalisib, Copanlisib, Duvelisib, and Alpelisib were approved by the FDA for the treatment of different types of cancer and several other PI3K inhibitors are currently under active clinical development. So far clinical candidates are non-selective kinase inhibitors with various off-target liabilities due to cross-reactivities. Hence, there is a need for the discovery of isoform-selective inhibitors with improved efficacy and fewer side-effects. The development of isoform-selective inhibitors is essential to reveal the unique functions of each isoform and its corresponding therapeutic potential. Although the clinical effect and relative benefit of pan and isoformselective inhibition will ultimately be determined, with the development of drug resistance and the demand for next-generation inhibitors, it will continue to be of great significance to understand the potential mechanism of isoform-selectivity. Because of the important role of type I PI3K family members in various pathophysiological processes, isoform-selective PI3K inhibitors may ultimately have considerable efficacy in a wide range of human diseases. This review summarizes the progress of isoformselective PI3K inhibitors in preclinical and early clinical studies for anticancer and other various diseases.

The Role of Toll-Like Receptors and Type I Interferons in Host Responses to Bacteria

2009 ◽  
Vol 5 (2) ◽  
pp. 143-149
Author(s):  
Marja Ojaniemi ◽  
Mari Liljeroos ◽  
Reetta Vuolteenaho
Keyword(s):  
Type I Interferons ◽  
Host Responses ◽  
Type I ◽  
Toll Like Receptors

scholarly journals Matrix degradation and cell proliferation are coupled to promote invasion and escape from an engineered human breast microtumor

2021 ◽  
Vol 13 (1) ◽  
pp. 17-29
Author(s):  
Emann M Rabie ◽  
Sherry X Zhang ◽  
Andreas P Kourouklis ◽  
A Nihan Kilinc ◽  
Allison K Simi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Type I ◽  
Matrix Degradation ◽  
Human Breast ◽  
Rate Of Invasion

Abstract Metastasis, the leading cause of mortality in cancer patients, depends upon the ability of cancer cells to invade into the extracellular matrix that surrounds the primary tumor and to escape into the vasculature. To investigate the features of the microenvironment that regulate invasion and escape, we generated solid microtumors of MDA-MB-231 human breast carcinoma cells within gels of type I collagen. The microtumors were formed at defined distances adjacent to an empty cavity, which served as an artificial vessel into which the constituent tumor cells could escape. To define the relative contributions of matrix degradation and cell proliferation on invasion and escape, we used pharmacological approaches to block the activity of matrix metalloproteinases (MMPs) or to arrest the cell cycle. We found that blocking MMP activity prevents both invasion and escape of the breast cancer cells. Surprisingly, blocking proliferation increases the rate of invasion but has no effect on that of escape. We found that arresting the cell cycle increases the expression of MMPs, consistent with the increased rate of invasion. To gain additional insight into the role of cell proliferation in the invasion process, we generated microtumors from cells that express the fluorescent ubiquitination-based cell cycle indicator. We found that the cells that initiate invasions are preferentially quiescent, whereas cell proliferation is associated with the extension of invasions. These data suggest that matrix degradation and cell proliferation are coupled during the invasion and escape of human breast cancer cells and highlight the critical role of matrix proteolysis in governing tumor phenotype.

scholarly journals Role of the Innate Immunity Signaling Pathway in the Pathogenesis of Sjögren’s Syndrome

2021 ◽  
Vol 22 (6) ◽  
pp. 3090
Author(s):  
Toshimasa Shimizu ◽  
Hideki Nakamura ◽  
Atsushi Kawakami
Keyword(s):  
Immune Responses ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Innate Immune ◽  
Type I ◽  
Type I Ifn ◽  
Adaptive Immune ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of the salivary and lacrimal glands and extra-glandular lesions. Adaptive immune response including T- and B-cell activation contributes to the development of SS. However, its pathogenesis has not yet been elucidated. In addition, several patients with SS present with the type I interferon (IFN) signature, which is the upregulation of the IFN-stimulated genes induced by type I IFN. Thus, innate immune responses including type I IFN activity are associated with SS pathogenesis. Recent studies have revealed the presence of activation pattern recognition receptors (PRRs) including Toll-like receptors, RNA sensor retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, and inflammasomes in infiltrating and epithelial cells of the salivary glands among patients with SS. In addition, the activation of PRRs via the downstream pathway such as the type I IFN signature and nuclear factor kappa B can directly cause organ inflammation, and it is correlated with the activation of adaptive immune responses. Therefore, this study assessed the role of the innate immune signal pathway in the development of inflammation and immune abnormalities in SS.

scholarly journals The Dynamic Interaction between Extracellular Matrix Remodeling and Breast Tumor Progression

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1046
Author(s):  
Jorge Martinez ◽  
Patricio C. Smith
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Cell Metabolism ◽  
Breast Tumors ◽  
Extracellular Matrix Remodeling ◽  
Type I ◽  
Matrix Remodeling ◽  
Desmoplastic Reaction ◽  
The Impact

Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this type of lesion, a property that allows its palpation and early detection. Fibrillar type I collagen is a major component of tumor desmoplasia and its accumulation is causally linked to tumor cell survival and metastasis. For many years, the desmoplastic phenomenon was considered to be a reaction and response of the host tissue against tumor cells and, accordingly, designated as “desmoplastic reaction”. This notion has been challenged in the last decades when desmoplastic tissue was detected in breast tissue in the absence of tumor. This finding suggests that desmoplasia is a preexisting condition that stimulates the development of a malignant phenotype. With this perspective, in the present review, we analyze the role of extracellular matrix remodeling in the development of the desmoplastic response. Importantly, during the discussion, we also analyze the impact of obesity and cell metabolism as critical drivers of tissue remodeling during the development of desmoplasia. New knowledge derived from the dynamic remodeling of the extracellular matrix may lead to novel targets of interest for early diagnosis or therapy in the context of breast tumors.

scholarly journals Role of Alternative Splicing in Regulating Host Response to Viral Infection

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1720
Author(s):  
Kuo-Chieh Liao ◽  
Mariano A. Garcia-Blanco
Keyword(s):  
Innate Immunity ◽  
Alternative Splicing ◽  
Immune Responses ◽  
Viral Infection ◽  
Rna Splicing ◽  
Type I ◽  
Host Immune Responses ◽  
Transcriptional Regulatory Mechanisms ◽  
Host Virus Interactions

The importance of transcriptional regulation of host genes in innate immunity against viral infection has been widely recognized. More recently, post-transcriptional regulatory mechanisms have gained appreciation as an additional and important layer of regulation to fine-tune host immune responses. Here, we review the functional significance of alternative splicing in innate immune responses to viral infection. We describe how several central components of the Type I and III interferon pathways encode spliced isoforms to regulate IFN activation and function. Additionally, the functional roles of splicing factors and modulators in antiviral immunity are discussed. Lastly, we discuss how cell death pathways are regulated by alternative splicing as well as the potential role of this regulation on host immunity and viral infection. Altogether, these studies highlight the importance of RNA splicing in regulating host–virus interactions and suggest a role in downregulating antiviral innate immunity; this may be critical to prevent pathological inflammation.

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