Minimally Invasive Spine Surgery for Lumbar Decompression or Disc Herniation.

Many people experience low back pain caused by degenerative disease of the lumbar spine; this includes spinal stenosis, spondylolisthesis, disc degeneration, and disc herniation. Conservative management of degenerative disease, which includes physical therapy, lifestyle modifications, and medications, is the initial approach. If this approach fails, a surgical procedure may be the next step.

Encephaloduroarteriosynangiosis Procedure: A Treatment Option for Patients With Moyamoya Disease.

Moyamoya disease is a progressive cerebrovascular disorder for which there is no cure. It is characterized by narrowing of and occlusions in the blood vessels that supply the brain, which causes a fine vascular network to develop to serve as collateral pathways. Moyamoya disease can lead to a reduction of blood flow to the brain and increase the risk of stroke.

Readministration of high-dose adeno-associated virus gene therapy vectors enabled by ImmTOR nanoparticles combined with B cell-targeted agents.

Tolerogenic ImmTOR nanoparticles encapsulating rapamycin have been demonstrated to mitigate immunogenicity of adeno-associated virus (AAV) gene therapy vectors, enhance levels of transgene expression, and enable redosing of AAV at moderate vector doses of 2 to 5E12 vg/kg. However, recent clinical trials have often pushed AAV vector doses 10-fold to 50-fold higher, with serious adverse events observed at the upper range. Here, we assessed combination therapy of ImmTOR with B cell-targeting drugs for the ability to increase the efficiency of redosing at high vector doses.

Rapamycin nanoparticles increase the therapeutic window of engineered interleukin-2 and drive expansion of antigen-specific regulatory T cells for protection against autoimmune disease.

Interleukin-2 (IL-2) therapies targeting the high affinity IL-2 receptor expressed on regulatory T cells (Tregs) have shown promising therapeutic benefit in autoimmune diseases through nonselective expansion of pre-existing Treg populations, but are potentially limited by the inability to induce antigen-specific Tregs, as well as by dose-limiting activation of effector immune cells in settings of inflammation. We recently developed biodegradable nanoparticles encapsulating rapamycin, called ImmTOR, which induce selective immune tolerance to co-administered antigens but do not increase total Treg numbers. Here we demonstrate that the combination of ImmTOR and an engineered Treg-selective IL-2 variant (termed IL-2 mutein) increases the number and durability of total Tregs, as well as inducing a profound synergistic increase in antigen-specific Tregs when combined with a target antigen.

Robotic-Assisted Lumbar Fusion: An Effective Technique for Pedicle Screw Placement.

Degenerative lumbar disease is a common condition in which progressive deterioration of the structures in the spine causes severely incapacitating pain and disability. Conservative management, including passive or active physical therapy, activity modification, and medications (eg, anti-inflammatory medications, oral and injectable steroids, opioids), may provide relief. However, when conservative management is unsuccessful or patients experience symptoms for an extended period of time, they may require spine surgery.

ImmTOR nanoparticles enhance AAV transgene expression after initial and repeat dosing in a mouse model of methylmalonic acidemia.

A major barrier to adeno-associated virus (AAV) gene therapy is the inability to re-dose patients due to formation of vector-induced neutralizing antibodies (Nabs). Tolerogenic nanoparticles encapsulating rapamycin (ImmTOR) provide long-term and specific suppression of adaptive immune responses, allowing for vector re-dosing. Moreover, co-administration of hepatotropic AAV vectors and ImmTOR leads to an increase of transgene expression even after the first dose.

Decompressive Hemicraniectomy for Middle Cerebral Artery Stroke: Indications and Perioperative Care.

Decompressive hemicraniectomy (DHC) is a procedure performed in the setting of malignant cerebral edema after a large middle cerebral artery stroke. The decision to proceed with surgical decompression is one that must be made judiciously and rapidly. Although this can be a life-saving surgery, it does not necessarily improve the patient's quality of life.

Enhancement of the Tolerogenic Phenotype in the Liver by ImmTOR Nanoparticles.

ImmTOR biodegradable nanoparticles encapsulating rapamycin have been shown to induce a durable tolerogenic immune response to co-administered biologics and gene therapy vectors. Prior mechanism of action studies have demonstrated selective biodistribution of ImmTOR to the spleen and liver following intravenous (IV) administration. In the spleen, ImmTOR has been shown to induce tolerogenic dendritic cells and antigen-specific regulatory T cells and inhibit antigen-specific B cell activation.

Enhancement of liver-directed transgene expression at initial and repeat doses of AAV vectors admixed with ImmTOR nanoparticles.

Systemic AAV (adeno-associated virus) gene therapy is a promising approach for the treatment of inborn errors of metabolism, but questions remain regarding its potency and durability. Tolerogenic ImmTOR nanoparticles encapsulating rapamycin have been shown to block the formation of neutralizing anti-capsid antibodies, thereby enabling vector re-administration. Here, we further demonstrate that ImmTOR admixed with AAV vectors also enhances hepatic transgene expression at the initial dose of AAV vector, independent of its effects on adaptive immunity.

Life without quality. Reflections of a female focus group on life, health and kidney disease.

Focus groups are increasingly employed in clinical practice as their flexible structure permits the range and depth of experiences of health service users and chronically ill individuals to be explored and recorded. A focus group workshop on quality of life was held in March 2007 involving a group of patients either awaiting transplantation, following transplantation, or with a family member who had already undergone renal replacement therapy (RRT). After intensive discussion the group produced the following consensus points.