Predictors of hematologic malignancy relapse in patients with advanced chronic graft-versus-host disease.

Malignancy relapse remains a major barrier to treatment success in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Chronic graft-versus-host disease (cGVHD) markedly reduces hematologic malignancy relapse risk, but relapses still occur in these patients. Patients (n = 275) with moderate or severe cGVHD were enrolled on the National Cancer Institute (NCI) prospective cross-sectional natural history study (NCT00092235).

Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48).

Objective: Biallelic mutations in the AP5Z1 gene encoding the AP-5 ζ subunit have been described in a small number of patients with hereditary spastic paraplegia (HSP) (SPG48); we sought to define genotype-phenotype correlations in patients with homozygous or compound heterozygous sequence variants predicted to be deleterious.

Methods: We performed clinical, radiologic, and pathologic studies in 6 patients with biallelic mutations in AP5Z1.

Results: In 4 of the 6 patients, there was complete loss of AP-5 ζ protein.

Longitudinal Study of Age-Related Cataract Using Dynamic Light Scattering: Loss of α-Crystallin Leads to Nuclear Cataract Development.

Purpose: To conduct a longitudinal study on age-related nuclear cataracts using dynamic light scattering (DLS) to determine if cataract progression is associated with loss of the unbound form of the lens molecular chaperone protein, α-crystallin.

Design: Natural history and cohort study.

Participants: Patients 30 years of age or older of either gender seeking treatment at the Wilmer Eye Institute Cornea-Cataract Department.

Predictive models for ocular chronic graft-versus-host disease diagnosis and disease activity in transplant clinical practice.

Ocular chronic graft-versus-host disease is one of the most bothersome common complications following allogeneic hematopoietic stem cell transplantation. The National Institutes of Health Chronic Graft-versus-Host Disease Consensus Project provided expert recommendations for diagnosis and organ severity scoring. However, ocular chronic graft-versus-host disease can be diagnosed only after examination by an ophthalmologist.

Biomarker-driven phase 2 study of MK-2206 and selumetinib (AZD6244, ARRY-142886) in patients with colorectal cancer.

Purpose: PI3K/AKT/mTOR and RAS/RAF/MEK pathways are frequently dysregulated in colorectal cancer (CRC). We conducted a biomarker-driven trial of the combination of MK-2206, an allosteric AKT 1/2/3 inhibitor, and selumetinib, a MEK 1/2 inhibitor, in patients with CRC to evaluate inhibition of phosphorylated ERK (pERK) and AKT (pAKT) in paired tumor biopsies.

Patients And Methods: Adult patients with advanced CRC were enrolled in successive cohorts stratified by KRAS mutation status.

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report.

The 2005 National Institutes of Health (NIH) Consensus Conference proposed new criteria for diagnosing and scoring the severity of chronic graft-versus-host disease (GVHD). The 2014 NIH consensus maintains the framework of the prior consensus with further refinement based on new evidence. Revisions have been made to address areas of controversy or confusion, such as the overlap chronic GVHD subcategory and the distinction between active disease and past tissue damage.

Web-based versus paper administration of common ophthalmic questionnaires: comparison of subscale scores.

Objective: To compare participants' responses to Web-based and paper-and-pencil versions of an ophthalmic, patient-reported outcome (PRO) questionnaire.

Design: Questionnaire development.

Participants: Matched subjects with ocular surface disease (OSD) (n = 68) and without OSD (controls, n = 50).

National Institutes of Health chronic graft-versus-host disease staging in severely affected patients: organ and global scoring correlate with established indicators of disease severity and prognosis.

Between 2004 and 2010, 189 adult patients were enrolled on the National Cancer Institute's cross-sectional chronic graft-versus-host disease (cGVHD) natural history study. Patients were evaluated by multiple disease scales and outcome measures, including the 2005 National Institutes of Health (NIH) Consensus Project cGVHD severity scores. The purpose of this study was to assess the validity of the NIH scoring variables as determinants of disease severity in severely affected patients in efforts to standardize clinician evaluation and staging of cGVHD.

Diagnosis and treatment of ocular chronic graft-versus-host disease: report from the German-Austrian-Swiss Consensus Conference on Clinical Practice in chronic GVHD.

Purpose: Ocular chronic graft-versus-host disease (cGVHD) is one of the most frequent long-term complications after hematopoietic stem cell transplantation and is often associated with significant morbidity and reduced quality of life.

Methods: The German/Austrian/Swiss Consensus Conference on Clinical Practice in cGVHD aimed to summarize the currently available evidence for diagnosis and (topical) treatment and to summarize different treatment modalities of ocular cGVHD. The presented consensus was based on a review of published evidence and a survey on the current clinical practice including transplant centers from Germany, Austria, and Switzerland.

Sclerotic-type chronic GVHD of the skin: clinical risk factors, laboratory markers, and burden of disease.

Chronic GVHD is one of the most severe complications of allogeneic HSCT. The sclerotic skin manifestations of cGVHD (ScGVHD) result from inflammation and fibrosis of the dermis, subcutaneous tissue, or fascia, leading to significant functional disability. Risk factors and clinical markers associated with ScGVHD remain largely unexamined.

Evaluation of the age-related eye disease study clinical lens grading system AREDS report No. 31.

Purpose: To examine the grading (interrater) reliability of the Age-Related Eye Disease Study (AREDS) Clinical Lens Grading System (ARLNS).

Design: Evaluation of diagnostic test or technology.

Participants: One hundred fifty volunteers (284 eyes).

Salivary gland involvement in chronic graft-versus-host disease: prevalence, clinical significance, and recommendations for evaluation.

Although xerostomia is a commonly reported complaint in patients with chronic graft-versus-host disease (cGVHD), criteria for evaluating the prevalence and characteristics of salivary gland involvement have not been well defined in this patient population. Previous studies also have made no distinction between salivary and mucosal oral cGVHD. We systematically evaluated signs and symptoms of sicca in a large cohort of patients with cGVHD (n = 101) using instruments widely used to study Sjogren's syndrome.

Clinical detection of precataractous lens protein changes using dynamic light scattering.

Objective: To use dynamic light scattering to clinically assess early precataractous lens protein changes.

Methods: We performed a cross-sectional study in 380 eyes of 235 patients aged 7 to 86 years with Age-Related Eye Disease Study clinical nuclear lens opacity grades 0 to 3.8.

Inhibition of the ATPase activity of the catalytic portion of ATP synthases by cationic amphiphiles.

Melittin, a cationic, amphiphilic polypeptide, has been reported to inhibit the ATPase activity of the catalytic portions of the mitochondrial (MF1) and chloroplast (CF1) ATP synthases. Gledhill and Walker [J.R.

A clinical study of the human lens with a dynamic light scattering device.

A study was conducted to determine the potential usefulness and repeatability of a new dynamic light scattering (DLS) device for clinical studies of the human lens and early cataract. Studies using the cold cataract model showed this new device to be more sensitive than the Scheimpflug cataract imaging system in detecting the earliest cataractous changes. A miniaturized clinical DLS device developed by NASA using fiber optic probes was mounted on a Keratoscope (Optikon 2000), which has a 3-dimensional aiming system for accurate repeated sampling of the same area of the lens.