The First Cold Atmospheric Plasma Phase I Clinical Trial for the Treatment of Advanced Solid Tumors: A Novel Treatment Arm for Cancer.

Local regional recurrence (LRR) remains the primary cause of treatment failure in solid tumors despite advancements in cancer therapies. Canady Helios Cold Plasma (CHCP) is a novel Cold Atmospheric Plasma device that generates an Electromagnetic Field and Reactive Oxygen and Nitrogen Species to induce cancer cell death. In the first FDA-approved Phase I trial (March 2020-April 2021), 20 patients with stage IV or recurrent solid tumors underwent surgical resection combined with intra-operative CHCP treatment.

Canady Cold Helios Plasma Reduces Soft Tissue Sarcoma Viability by Inhibiting Proliferation, Disrupting Cell Cycle, and Inducing Apoptosis: A Preliminary Report.

Soft tissue sarcomas (STS) are a rare and highly heterogeneous group of solid tumors, originating from various types of connective tissue. Complete removal of STS by surgery is challenging due to the anatomical location of the tumor, which results in tumor recurrence. Additionally, current polychemotherapeutic regimens are highly toxic with no rational survival benefit.

BCL2A1 regulates Canady Helios Cold Plasma-induced cell death in triple-negative breast cancer.

Breast cancer is the leading cause of cancer death among women. Triple-negative breast cancer (TNBC) has a poor prognosis and frequently relapses early compared with other subtypes. The Cold Atmospheric Plasma (CAP) is a promising therapy for prognostically poor breast cancer such as TNBC.

Canady Helios Cold Plasma Induces Breast Cancer Cell Death by Oxidation of Histone mRNA.

Breast cancer is the most common cancer among women worldwide. Its molecular receptor marker status and mutational subtypes complicate clinical therapies. Cold atmospheric plasma is a promising adjuvant therapy to selectively combat many cancers, including breast cancer, but not normal tissue; however, the underlying mechanisms remain unexplored.

The synergistic effect of Canady Helios cold atmospheric plasma and a FOLFIRINOX regimen for the treatment of cholangiocarcinoma in vitro.

Cholangiocarcinoma (CCA) is a rare biliary tract cancer with a low five-year survival rate and high recurrence rate after surgical resection. Currently treatment approaches include systemic chemotherapeutics such as FOLFIRINOX, a chemotherapy regimen is a possible treatment for severe CCA cases. A limitation of this chemotherapy regimen is its toxicity to patients and adverse events.

Randomized Controlled Trial Evidence of Cost-Effectiveness of a Multifaceted AKI Intervention Approach.

Introduction: Acute kidney injury (AKI) is associated with increased health care utilization and higher costs. The Tackling AKI study was a multicenter, pragmatic, stepped-wedge cluster randomized trial that demonstrated a reduced hospital length of stay after implementation of a multifaceted AKI intervention (e-alerts, care bundle, and an education program). We tested whether this would result in cost savings.

A Translational Model for Venous Thromboembolism: MicroRNA Expression in Hibernating Black Bears.

Background: Hibernating American black bears have significantly different clotting parameters than their summer active counterparts, affording them protection against venous thromboembolism during prolonged periods of immobility. We sought to evaluate if significant differences exist between the expression of microRNAs in the plasma of hibernating black bears compared with their summer active counterparts, potentially contributing to differences in hemostasis during hibernation.

Materials And Methods: MicroRNA sequencing was assessed in plasma from 21 American black bears in summer active (n = 11) and hibernating states (n = 10), and microRNA signatures during hibernating and active state were established using both bear and human genome.

Dehydrated Amnion/Chorion Improves Achilles Tendon Repair in a Diabetic Animal Model.

Introduction: Healing of tendon injuries is often plagued by significant scar formation and compromised biomechanical function. For those with diabetes, these injuries are further complicated by alterations to the extracellular matrix of the tendon, poor circulation, and delayed wound healing; consequently, complications and re-rupture rates for patients with diabetes are reported higher than the typical patient population. Placental derived membranes, specifically dehydrated human amnion/chorion membranes (dACMs), have been utilized clinically as an adhesion barrier, and these membranes have been shown to reduce scarring and aid in tissue repair.

The rationale for the new deceased donor pancreas allocation schema.

Background: To ensure the continued success of whole organ pancreas and islet transplantation, deceased donor pancreas allocation policy must continue to evolve.

Methods: To assess the existing system, the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing Kidney and Pancreas Transplant Committee retrospectively analyzed the disposition and outcomes of deceased donor pancreata in the United States between January 1, 2000 and December 31, 2003.

Results: During the time period studied, consent was obtained but the pancreas was not recovered in 48% (11,820) of organ donors.

Clinical results of an organ procurement organization effort to increase utilization of donors after cardiac death.

Background: To stimulate organ donation, an organ procurement organization (OPO)-wide effort was undertaken to increase donors after cardiac death (DCD) over a 5-year period. This included commonality of protocols, pulsatile perfusion of kidneys, centralization of data and a regional allocation variance designed to minimize cold ischemia times and encourage adoption of DCD protocols at transplant centers.

Results: In one OPO, eight centers initiated DCD programs in 11 hospitals.

Inhibition of apoptosis by survivin improves transplantation of pancreatic islets for treatment of diabetes in mice.

Survivin is a cancer gene implicated in inhibition of apoptosis and regulation of mitosis, but its function in normal cells has remained elusive. Here, we show that transgenic mice expressing survivin in pancreatic islet beta-cells show no changes in cell proliferation, as determined by islet size or islet number. Transplantation of survivin transgenic islets in diabetic recipient mice affords long-term engraftment and stable correction of hyperglycaemia.

Antigen exposure during enhanced CTLA-4 expression promotes allograft tolerance in vivo.

The role of CTLA-4 in tolerance is primarily inferred from knockout and blocking studies. Anti-CD45RB mediates allograft tolerance in mice by inducing CTLA-4 expression on CD4 cells, providing a novel opportunity to determine how therapeutic enhancement of CTLA-4 promotes tolerance. We now show that induced CTLA-4 expression normally resolves by day 17.

Gene silencing in the endocrine pancreas mediated by short-interfering RNA.

Objectives: RNA interference as mediated by short-interfering RNA (siRNA) offers a nonviral means to silence genes in tissue; however, few data exist about gene therapy using siRNA in pancreas tissue. To determine if siRNA treatment could silence an endogenous gene in pancreatic islets, we developed a murine model using the endocrine pancreas.

Methods: The insulin 2 (Ins2) gene was targeted with siRNA, and quantitative RT-PCR, fluorescent microscopy, and FACS were used to measure transcript levels and siRNA cellular uptake and transfection efficiency.

Requirements for induction and maintenance of peripheral tolerance in stringent allograft models.

Peripheral tolerance can be achieved in many but not all murine allograft models. The requirements for controlling more aggressive immune responsiveness and generating peripheral tolerance in stringent allograft models are unknown. Understanding these requirements will provide insight toward ultimately achieving tolerance in humans, which are also resistant.

Renal transplant recipients over aged 60 have diminished immune activity and a low risk of rejection.

Strict consideration of the renal transplant candidate's chronologic age is generally supplanted by more subjective reflection on his (her) physiologic state. In the US, patients over 64 years old represented 9.0% of renal transplant recipients in the year 2000, yet little prior experience is available with which to guide the management of geriatric patients.

Donor kidney exchanges.

Kidney transplantation from live donors achieves an excellent outcome regardless of human leukocyte antigen (HLA) mismatch. This development has expanded the opportunity of kidney transplantation from unrelated live donors. Nevertheless, the hazard of hyperacute rejection has usually precluded the transplantation of a kidney from a live donor to a potential recipient who is incompatible by ABO blood type or HLA antibody crossmatch reactivity.

Transplantation in the diabetic patient with advanced chronic kidney disease: a task force report.

On May 7 to 8, 2003, more than 60 physicians, surgeons, nurses, and allied health professionals met in Chicago, IL, to discuss state-of-the-art approaches to transplantation in the clinical management of patients with diabetes and advanced chronic kidney disease. Four work groups addressed pretransplantation evaluation and management, therapeutic alternatives for treatment of patients with chronic kidney disease, posttransplantation diabetes mellitus, and improving long-term kidney transplant outcomes in patients with diabetes. This report summarizes the deliberations and recommendations of the task force.

Cutting edge: transplantation tolerance through enhanced CTLA-4 expression.

Knockout and blocking studies have shown a critical role for CTLA-4 in peripheral tolerance, however, it is unknown whether augmenting CTLA-4 expression actually promotes tolerance. Here we demonstrate a specific and requisite role for CTLA-4 and its up-regulation in tolerance through anti-CD45RB. First, long-term murine islet allograft survival induced by anti-CD45RB is prevented by CTLA4-Ig, which interferes with B7:CTLA-4 interactions.

Prolonged islet allograft survival in diabetic NOD mice by targeting CD45RB and CD154.

Clinical islet transplantation is a successful procedure that can improve the quality of life in recipients with diabetes. A drawback of the procedure is the need for chronic administration of immunosuppressive drugs that, among other side effects, are potentially diabetogenic. Definition of immunosuppressive protocols that utilize nondiabetogenic compounds could further improve islet transplantation outcome.

Islet filtration: a simple and rapid new purification procedure that avoids ficoll and improves islet mass and function.

Islet isolation is a time-consuming process. Islet yields vary, and previous in vitro studies suggest that Ficoll may be an islet toxin. Here, we describe an alternative, Ficoll-free method to purify murine islets by filtration through a cell strainer.

Treatment of osteoporosis and osteopenia in long-term renal transplant patients with alendronate.

Bone mineral density (BMD) and biochemical markers of bone-turnover were evaluated in a 2-year study in 58 long-term renal transplant recipients with good renal function. In the first year of study, data were collected and patients with osteoporosis and parameters of high bone turnover were classified as being at high risk for on-going bone loss (Group A; n = 29). Patients with lesser degrees of bone loss or without biochemical parameters of high bone turnover were followed longitudinally (Group B; n = 29).