An insight into biomimetic 4D printing.

4D printed objects are indexed under additive manufacturing (AM) objects. The 4D printed materials are stimulus-responsive and have shape-changing features. However, the manufacturing of such objects is still a challenging task. For this, the designing space has to be explored in the initial stages, which is lagging so far. This paper encompasses two recent approaches to explore the conceptual design of 4D printed objects in detail: (a) an application-based modeling and simulation approach for phytomimetic structures and (b) a voxel-based modeling and simulation approach. The voxel-based modeling and simulation approach has the enhanced features for the rapid testing (prior to moving into design procedures) of the given distribution of such 4D printed smart materials (SMs) while checking for behaviors, particularly when these intelligent materials are exposed to a stimulus. The voxel-based modeling and simulation approach is further modified using bi-exponential expressions to encode the time-dependent behavior of the bio-inspired 4D printed materials. The shape-changing materials are inspired from biological objects, such as flowers, which are temperature-sensitive or touch-sensitive, and can be 4D printed in such a way that they are encrypted with a decentralized, anisotropic enlargement feature under a restrained alignment of cellulose fibers as in the case of composite hydrogels. Such plant-inspired architectures can change shapes when immersed in water. This paper also outlines a review of the 4D printing of (a) smart photocurable and biocompatible scaffolds with renewable plant oils, which can be a better alternative to traditional polyethylene glycol diacrylate (PEGDA) to support human bone marrow mesenchymal stem cells (hMSCs), and (b) a biomimetic dual shape-changing tube having applications in biomedical engineering as a bioimplant. The future applications would be based on these smart and intelligent materials; thus, it is important to modify the existing voxel-based modeling and simulation approach and discuss efficient printing methods to fabricate such bio-inspired materials.

Acute Disseminated Intravascular Coagulation after Oxaliplatin Infusion.

Oxaliplatin is one of the most commonly used drugs for patients with colorectal cancer. It has rarely been associated with disseminated intravascular coagulation (DIC) with only 3 previously reported cases. In all those instances, the patients had started receiving oxaliplatin, developed evidence of DIC during the course of planned treatment, and recovered with supportive care. We report a case of a 71-year-old man with colorectal cancer treated successfully with an oxaliplatin-based regimen who had disease relapse after 3 years. When treated again with oxaliplatin, he developed signs of an acute hypersensitivity reaction, and eventually had signs and symptoms consistent with DIC despite appropriate management. This case is unique in that a DIC reaction evolving from a hypersensitivity reaction occurred after the patient had already tolerated the drug years earlier. It suggests a possible immune-mediated etiology to this rare occurrence that should be kept in mind while utilizing this commonly employed drug.

Correction of factor XI deficiency by liver transplantation.

Orthotopic liver transplantation for other diseases typically results in a coincidental cure for hemophilia A and B; however, long-term outcomes of liver transplant in hemophilia C are not very well described. Herein, the authors report a patient of severe congenital factor XI (FXI) deficiency who received an orthotopic liver transplant. The authors discuss the perioperative management and long-term outcomes. The normalization of his FXI levels confirms that the liver is the most clinically relevant site of synthesis of FXI.

Whole exome sequencing of a patient with metastatic hidradenocarcinoma and review of the literature.

Hidradenocarcinoma is a rare malignancy of the sweat glands with only a few cases reported in literature. The management of these tumors is based on the extent of disease with local disease managed with surgical resection. These can tumors carry a high potential of lymphatic and vascular spread and local and distant metastases are not uncommon. Given the rarity of the tumor and lack of genetic and clinical data about these tumors, there is no consensus on the proper management of metastatic disease. Here in we report the first case of metastatic hidradenocarcinoma with detailed molecular profiling including whole exome sequencing. We identified mutations in multiple genes including two that are potentially targetable: PTCH1 and TCF7L1. Further work is necessary to not only confirm the presence of these mutations but also to confirm the clinical significance.

Excellent Outcome of Immunomodulation or Bruton's Tyrosine Kinase Inhibition in Highly Refractory Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare diffuse large B-cell lymphoma confined to the skin of the legs. The typical presentation is characterized by solitary or multiple growing plaques, usually confined to one leg. We report a case of PCDLBCL-LT of activated B-cell subtype characterized by multiple local relapses in the legs, initially, and systemic relapses about seven years after the diagnosis. Local relapses were sensitive to radiation therapy. Cutaneous and systemic relapses responded well to immunomodulatory therapy with lenalidomide followed by Bruton's tyrosine kinase inhibition with ibrutinib. Ibrutinib is the only treatment that resulted in long-lasting complete remission. Lenalidomide and especially ibrutinib appear to have a significant activity against this lymphoma and should be incorporated in the treatment of this resistant and aggressive lymphoma. To our knowledge, this is the first case of PCDLBCL-LT reported in the literature exhibiting a complete response to ibrutinib.

Changing paradigms in management of metastatic Castration Resistant Prostate Cancer (mCRPC).

Recently, the standard of care for metastatic Castration Resistant Prostate Cancer (mCRPC) has changed considerably. Persistent androgen receptor (AR) signaling has been identified as a target for novel therapies and reengages the fact that AR continues to be the primary target responsible for metastatic prostate cancer. Androgen receptor gene amplification and over expression have been found to result in a higher concentration of androgen receptors on tumor cells, making them extremely sensitive to low levels of circulating androgens. Additionally, prostate cancer cells are able to maintain dihydrotestosterone (DHT) concentration in excess of serum concentrations to support tumor growth. For many years ketoconazole was the only CYP17 inhibitor that was used to treat mCRPC. However, significant toxicities limit its use. Newly approved chemotherapeutic agents such as Abiraterone (an oral selective inhibitor of CYP17A), which blocks androgen biosynthesis both within and outside the prostate cancer cells), and enzalutamide (blocks AR signaling) have improved overall survival. There are also ongoing phase III trials for Orteronel (TAK- 700), ARN- 509 and Galeterone (TOK-001), which targets androgen signaling. In this review, we will present the rationale for the newly approved hormonal treatments, their indications and complications, and we will discuss ongoing trials that are being done to improve the efficacy of the approved agents. Finally, we will talk about the potential upcoming hormonal treatments for mCRPC.

Syncytial giant cell hepatitis associated with chronic lymphocytic leukemia: a case report.

BACKGROUND: Syncytial giant cell hepatitis (GCH) is an uncommon and an underreported disease entity. In two previously reported cases of GCH in patients with Chronic Lymphocytic Leukemia (CLL) liver failure ensued. Autoimmune and infective causes have been implicated but its etiology remains unclear. CASE PRESENTATION: A 60-year-old female with CLL presented with acute hepatitis with negative viral and auto-immune serologies and without any prior toxic exposure. Liver biopsy showed typical histological features of GCH. The patient was successfully treated with corticosteroids and intravenous immunoglobulin (IVIG). Her liver enzymes returned to baseline and have remained normal as of the last follow up almost 4 years later. CONCLUSIONS: Association of GCH with CLL may be under recognized. Clinical suspicion of GCH in CLL patients with serology-negative hepatitis, early liver biopsy and therapeutic intervention may influence outcome. This is the first case report of successful treatment of GCH in CLL patients. Moreover, our case also demonstrates the ability to resume effective CLL therapy post-GCH diagnosis without detriment to the liver.