Long-term response with the atypical reaction to nivolumab in microsatellite stability metastatic colorectal cancer: A case report.

Immunotherapy has become an integral part of a comprehensive treatment approach to metastatic colorectal cancer (mCRC). Nivolumab (Opdivo) is a human immunoglobulin G4 monoclonal antibody that blocks the interaction between the programmed cell death 1 (PD-1) receptor and its ligands 1/2 (PD-L1/PD-L2), leading to inhibition of T-cell proliferation, cytokine secretion, and enhanced immune response. The US Food and Drug Administration (FDA) has approved this drug for use in high microsatellite instability (MSI-high)/deficiencies in mismatch repair (dMMR) advanced CRC patients.

Analysis of Circulating Tumor and Cancer Stem Cells Provides New Opportunities in Diagnosis and Treatment of Small Cell Lung Cancer.

Current methods for diagnosis and treatment of small cell lung cancer (SCLC) have only a modest efficacy. In this pilot study, we analyzed circulating tumor cells (CTCs) and cancer stem cells (CSCs) in patients with SCLC to search for new diagnostic and prognostic markers and novel approaches to improve the treatment of the disease. In other forms of lung cancer, we showed a heterogeneity of blood CTCs and CSCs populations, as well as changes in other cell populations (ALDH, CD87CD276, and EGFAxl) in smokers.

Parameters of Tumor Microenvironment Determine Effectiveness of Anti-PD-1/PD-L1 Therapy.

Undoubtedly, one of the most promising approaches to the treatment of cancer is creation of the pathogenetically based therapeutic drugs. Researchers from all over the world are trying to answer the question on how to select a target that would be effective and, in general, they are quite successful at that. The Nobel Prize-winning discovery of mechanisms for regulating activity of the immune system cells through checkpoint molecules, as well as discovery of the ability of tumor cells to use these mechanisms to suppress immune responses was an impetus for the development of modern immunotherapy, and now such inhibitors of the immune checkpoints as PD-1/PD-L1 are included in the routine chemotherapy.

The Role of Natriuretic Peptides in the Regulation of Cardiac Tolerance to Ischemia/Reperfusion and Postinfarction Heart Remodeling.

In the past 10 years, mortality from acute myocardial infarction has not decreased despite the widespread introduction of percutaneous coronary intervention. The reason for this situation is the absence in clinical practice of drugs capable of preventing reperfusion injury of the heart with high efficiency. In this regard, noteworthy natriuretic peptides (NPs) which have the infarct-limiting effect, prevent reperfusion cardiac injury, prevent adverse post-infarction remodeling of the heart.

A micro-architecturally biomimetic collagen template for mesenchymal condensation based cartilage regeneration.

Unlabelled: The unique arcade-like orientation of collagen fibers enables cartilage to bear mechanical loads. In this study continuous-length aligned collagen threads were woven to emulate the interdigitated arcade structure of the cartilage. The weaving pattern provided a macropore network within which micromass cell pellets were seeded to take advantage of mesenchymal condensation driven chondrogenesis.

Implant Size Availability Affects Reproduction of Distal Femoral Anatomy.

A total knee arthroplasty system offers more distal femoral implant anterior-posterior (AP) sizes than its predecessor. The purpose of this study is to investigate the impact of increased size availability on an implant system's ability to reproduce the AP dimension of the native distal femur. We measured 200 cadaveric femora with the AP-sizing guides of Zimmer (Warsaw, IN) NexGen (8 sizes) and Zimmer Persona (12 sizes) total knee arthroplasty systems.

Important Differences Exist in Posterior Condylar Offsets in an Osteological Collection of 1,058 Femurs.

Posterior condylar offset (PCO) has important implications in total knee arthroplasty (TKA) function and design. In an osteological study of 1,058 femurs, we measured PCO using two separate techniques with a 3D digitizer. Measurements were standardized for the size of the femur.

Frequency of EGFR mutations in non-small cell lung cancer patients: screening data from West Siberia.

Background: Incorporation of molecular analysis of the epidermal growth factor receptor (EGFR) gene into routine clinical practice has shown great promise to provide personalized therapy of the non-small cell lung cancer (NSCLC) in the developed world. However, the genetic testing of EGFR mutations has not yet become routine clinical practice in territories remote from the central regions of Russia. Therefore, we aimed to study the frequency of major types of activating mutations of the EGFR gene in NSCLC patients residing in West Siberia.

Machine oil inhibits the osseointegration of orthopaedic implants by impairing osteoblast attachment and spreading.

The most important factor contributing to short-term and long-term success of cementless total joint arthroplasties is osseointegration. Osseointegration leads to a direct structural and functional connection between living bone and the surface of an implant. Surface contaminants may remain on orthopaedic implants after sterilization procedures and impair osseointegration.

An initial experience with hip resurfacing versus cementless total hip arthroplasty.

Background: Hip resurfacing is an alternative to total hip arthroplasty.

Questions/purpose: We aimed to compare an experienced hip surgeon's initial clinical results of hip resurfacing with a new cementless total hip arthroplasty (THA).

Methods: The first 55 consecutive hip resurfacing arthroplasties were compared to 100 consecutive cementless THAs using a cylindrical tapered femoral stem.

The shape of the proximal femur influences acetabular wear patterns over time.

Background: Femoroacetabular impingement has been proposed as a cause of early osteoarthritis, but it is not known how this develops over time or whether the shape of the proximal femur influences this risk.

Questions/purposes: (1) Which areas of the acetabulum are worn more frequently by individuals with a cam deformity of the proximal femur? (2) Do observed acetabular wear patterns differ based on the etiology of the cam deformity? (3) Do wear patterns of individuals with a cam deformity differ based on an individual's age?

Methods: We examined 645 corresponding femora and acetabuli from the Hamann-Todd Osteological Collection and determined the offset and alpha angle using photographs; 370 specimens met inclusion criteria and were examined for signs of wear and the locations of wear were recorded. Specimens were separated into eight subgroups based on age either younger than 40 years or older than 60 years, alpha angle greater or less than 55°, and degree of anterior head-neck offset.

Micrometer scale guidance of mesenchymal stem cells to form structurally oriented cartilage extracellular matrix.

Tissue engineering is a possible method for long-term repair of cartilage lesions, but current tissue-engineered cartilage constructs have inferior mechanical properties compared to native cartilage. This problem may be due to the lack of an oriented structure in the constructs at the microscale that is present in the native tissue. In this study, we utilize contact guidance to develop constructs with microscale architecture for improved chondrogenesis and function.

Adherent lipopolysaccharide inhibits the osseointegration of orthopedic implants by impairing osteoblast differentiation.

Osseointegration is the process by which an orthopedic implant makes direct bone-to-implant contact and is crucial for the long-term function of the implant. Surface contaminants, such as bacterial debris and manufacturing residues, may remain on orthopedic implants after sterilization and impair osseointegration. For example, specific lots of implants that were associated with impaired osseointegration and high failure rates were discovered to have contaminants including bacterial debris.

Predictors of range of motion in patients undergoing manipulation after TKA.

Background: Knee stiffness or limited range of motion (ROM) after total knee arthroplasty (TKA) may compromise patient function. Patients with stiffness are usually managed with manipulation under anesthesia (MUA) to improve ROM. However, the final ROM obtained is multifactorial and may depend on factors such as comorbidities, implant type, or the timing of MUA.

Retrieval analysis of Harris-Galante I and II acetabular liners in situ for more than 10 years.

Background And Purpose: There have been few reports documenting the wear and oxidation performance of the polyethylene bearing surface of HGPI and HGPII THA devices. We evaluated retrieved HGPI and HGPII acetabular liners that had been in situ for more than 10 years and determined whether there was a relationship between clinical and radiographic factors, surface damage, wear, and oxidation.

Materials And Methods: 129 HGPI and II acetabular liners with implantation times of > 10 years were retrieved at 4 institutions between 1997 and 2010.

Surface contaminants inhibit osseointegration in a novel murine model.

Surface contaminants, such as bacterial debris and manufacturing residues, may remain on orthopedic implants after sterilization procedures and affect osseointegration. The goals of this study were to develop a murine model of osseointegration in order to determine whether removing surface contaminants enhances osseointegration. To develop the murine model, titanium alloy implants were implanted into a unicortical pilot hole in the mid-diaphysis of the femur and osseointegration was measured over a five week time course.

Nondestructive evaluation of hydrogel mechanical properties using ultrasound.

The feasibility of using ultrasound technology as a noninvasive, nondestructive method for evaluating the mechanical properties of engineered weight-bearing tissues was evaluated. A fixture was designed to accurately and reproducibly position the ultrasound transducer normal to the test sample surface. Agarose hydrogels were used as phantoms for cartilage to explore the feasibility of establishing correlations between ultrasound measurements and commonly used mechanical tissue assessments.

Post damage in contemporary posterior-stabilized tibial inserts: influence of implant design and clinical relevance.

The mechanisms of damage at the polyethylene post in 3 contemporary tibial insert designs were evaluated and compared with a historical standard (Insall-Burstein II; Zimmer, Warsaw, Ind). One hundred five gamma sterilized posterior-stabilized tibial inserts were revised after an average of 4.7 years (0.

Intra-articular hyaluronans: the treatment of knee pain in osteoarthritis.

The etiology of pain in osteoarthritis is multifactoral, and includes mechanical and inflammatory processes. Intra-articular injections of hyaluronans (HAs) are indicated when non-pharmacological and simple analgesics have failed to relieve symptoms. The HAs appear to reduce pain by restoring both mechanical and biomechanical homeostasis in the joint.

Revision of hip resurfacing arthroplasty.

Metal-on-metal (MOM) hip resurfacing has become an increasingly popular treatment for young, active patients with degenerative disease of the hip, as bearing surfaces with better wear properties are now available. One proposed advantage of resurfacing is its ability to be successfully revised to total hip arthroplasty (THA). In addition, radiographic parameters that may predict failure in hip resurfacing have yet to be clearly defined.

Incidence of postthrombotic syndrome in patients undergoing primary total hip arthroplasty for osteoarthritis.

Background: Postthrombotic syndrome (PTS) is a chronic condition in the lower extremity that develops after deep vein thrombosis (DVT). The incidence of PTS after total hip arthroplasty (THA) is not well established.

Questions/purposes: We (1) determined the incidence of PTS after DVT in patients undergoing primary THA for osteoarthritis; and (2) determined whether the incidence of PTS was greater in patients with DVT than without.

Bacterial pathogen-associated molecular patterns stimulate biological activity of orthopaedic wear particles by activating cognate Toll-like receptors.

Aseptic loosening of orthopaedic implants is induced by wear particles generated from the polymeric and metallic components of the implants. Substantial evidence suggests that activation of Toll-like receptors (TLRs) may contribute to the biological activity of the wear particles. Although pathogen-associated molecular patterns (PAMPs) produced by Gram-positive bacteria are likely to be more common in patients with aseptic loosening, prior studies have focused on LPS, a TLR4-specific PAMP produced by Gram-negative bacteria.

Hemostasis using a bipolar sealer in primary unilateral total knee arthroplasty.

Previous studies have shown that, compared with standard electrocautery, a bipolar sealer reduces tissue damage and smoke production during surgery. We conducted a multicenter, prospective, randomized study to compare a bipolar sealer with standard electrocautery for hemostasis. Sixty-nine primary total knee arthroplasties were performed.