The Duration of Thigh Tourniquet Use Associated With Anterior Cruciate Ligament Reconstruction Does Not Produce Cellular-Level Contractile Dysfunction of the Quadriceps Muscle at 3 Weeks After Surgery.

BACKGROUND: Anterior cruciate ligament (ACL) trauma and ACL reconstruction (ACLR) are associated with the loss of strength and function of the muscles that span the knee joint. The underlying mechanism associated with this is not completely understood. PURPOSE: To determine whether the duration of tourniquet use during ACLR has an effect on knee extensor muscle contractile function and size at the cellular (ie, fiber) level 3 weeks after surgery and at the whole-muscle level at 6 months after surgery. STUDY DESIGN: Descriptive laboratory study and case series; Level of evidence, 4. METHODS: Study participants sustained an acute, first-time ACL injury. All participants underwent ACLR with the use of a tourniquet placed in a standardized location on the thigh; the tourniquet was inflated (pressure range, 250-275 mm Hg), and the time of tourniquet use during surgery was documented. Participants were evaluated 1 week before surgery (to measure patient function, strength, and subjective outcome with the Knee injury and Osteoarthritis Outcome Score [KOOS] and International Knee Documentation Committee [IKDC] score), at 3 weeks after ACLR surgery (to obtain muscle biopsy specimens of the vastus lateralis and assess muscle fiber cross-sectional area, contractile function, and mitochondrial content and morphometry), and at 6 months after ACLR (to evaluate patient function, strength, and subjective outcomes via KOOS and IKDC scores). Data were acquired on both the injured/surgical limb and the contralateral, normal side to facilitate the use of a within-subjects study design. Results are based on additional analysis of data acquired from previous research that had common entry criteria, treatments, and follow-up protocols. RESULTS: At 3 weeks after ACLR, the duration of tourniquet use at the time of surgery did not explain the variation in single-muscle fiber contractile function or cross-sectional area (myosin heavy chain [MHC] I and II fibers) or subsarcolemmal and intermyofibrillar mitochondrial content or morphometry. At 6 months after ACLR, the duration of tourniquet use was not associated with the peak isometric and isokinetic torque measurements, patient function, or patient-reported outcomes. CONCLUSION: The duration of tourniquet use at the time of ACLR surgery did not explain variation in muscle fiber size, contractile function, or mitochondrial content at 3 weeks after surgery or strength of the quadriceps musculature or patient-reported function or quality of life at 6-month follow-up.

Ultrasound and Clinical Measures for Lymphedema.

BACKGROUND: Treatment for breast cancer has increased patient survivorship exponentially over the past few decades. With increased survivorship, more women are living with the longstanding effects of breast cancer treatment, such as lymphedema. Patients, health care providers, and payers depend on practical and efficient clinical measures to accurately diagnose and monitor disease progression or regression. However, current clinical measures do not include objective measures that assess lymphedetamous tissue accurately. This study compared current measures to a novel use of ultrasound (US) imaging to quantify tissue texture. METHODS AND RESULTS: Seventeen women diagnosed with lymphedema completed self-report questionnaires and then were tested twice by two lymphedema physical therapists who measured edema, fibrosis, and limb volume differences. One therapist measured subjects' limbs using US imaging and derived measures of entropy and average pixel intensity. Volume measures were consistent between therapists (p < 0.01) but palpation was not (0.01 < p < 0.72). Therapists' measures correlated better to subjects' self-report of edema (0.01 < p > 0.32) as compared to fibrosis (0.23 < p > 0.90). US measures were reliable (Cronbachs's α = 0.7 and 0.91 for entropy and API, respectively). Entropy measures demonstrated significant differences between subjects' involved versus uninvolved forearms (p = 0.03). CONCLUSIONS: Therapists were not consistent with each other when rating edema or fibrosis; however, they were consistent when measuring limb volume differences. US measures (entropy) demonstrated a significant difference between involved and uninvolved. US imaging, as a tool to quantify subcutaneous tissues, holds promise to be a safe, mobile, and effective method to measure lymphedema tissue texture.

A Phase 1 Trial of TPI 287 as a Single Agent and in Combination With Temozolomide in Patients with Refractory or Recurrent Neuroblastoma or Medulloblastoma.

BACKGROUND: The primary aim of this Phase I study was to determine the maximum tolerated dose (MTD) of TPI 287 and the safety and tolerability of TPI 287 alone and in combination with temozolomide (TMZ) in pediatric patients with refractory or recurrent neuroblastoma or medulloblastoma. The secondary aims were to evaluate the pharmacokinetics of TPI 287 and the treatment responses. PROCEDURE: Eighteen patients were enrolled to a phase I dose escalation trial of weekly intravenous infusion of TPI 287 for two 28-day cycles with toxicity monitoring to determine the MTD, followed by two cycles of TPI 287 in combination with TMZ. Samples were collected to determine the pharmacokinetic parameters C(max), AUC(0-24), t(1/2), CL, and Vd on day 1 of cycles 1 (TPI 287 alone) and 3 (TPI 287 + TMZ) following TPI 287 infusion. Treatment response was evaluated by radiographic (CT or MRI) and radionuclide (MIBG) imaging for neuroblastoma. RESULTS: We determined the MTD of TPI 287 alone and in combination with temozolomide to be 125 mg/m(2). The non-dose-limiting toxicities at this dose were mainly anorexia and pain. The dose-limiting toxicities (DLTs) of two patients at 135 mg/m(2) were grade 3 hemorrhagic cystitis and grade 3 sensory neuropathy. CONCLUSIONS: Overall, TPI 287 was well tolerated by pediatric patients with refractory and relapsed neuroblastoma and medulloblastoma at a dose of 125 mg/m(2) IV on days 1, 8, and 15 of a 28 day cycle.