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Diffusion basis spectrum imaging (DBSI) combines discrete anisotropic diffusion tensors and the spectrum of isotropic diffusion tensors to model the underlying multiple sclerosis (MS) pathologies. We used clinical MS subtypes as a surrogate of underlying pathologies to assess DBSI as a biomarker of pathology in 55 individuals with MS. Restricted isotropic fraction (reflecting cellularity) and fiber fraction (representing apparent axonal density) were the most important DBSI metrics to classify MS using brain white matter lesions. These DBSI metrics outperformed lesion volume. When analyzing the normal‐appearing corpus callosum, the most significant DBSI metrics were fiber fraction, radial diffusivity (reflecting myelination), and nonrestricted isotropic fraction (representing edema). This study provides preliminary evidence supporting the ability of DBSI as a potential noninvasive biomarker of MS neuropathology. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES: The incidence of myeloma in older adults is increasing, yet little is known about geriatric impairments in these patients. We aimed to examine the prevalence of geriatric impairments in older adults with myeloma and the association between geriatric assessment and autologous stem cell transplant eligibility. DESIGN: Prospective cohort study. SETTING: Two academic medical centers. PARTICIPANTS: A total of 40 adults 65 years and older with newly diagnosed myeloma were enrolled. MEASUREMENT: Participants completed a primarily self‐administered geriatric assessment, including measures of functional status, comorbidities, polypharmacy, psychosocial status, social support, quality of life, cognition, and physical performance. Outcomes were autologous stem cell transplant eligibility and receipt. RESULTS: Forty patients enrolled; their mean age was 71 years. Geriatric impairments were common: 62% reported dependence in one or more instrumental activities of daily living (IADL), 76.9% had polypharmacy (four or more medications), and 47.5% had one or more comorbidities. Median time on the Timed Up and Go was 13.3 ± 4.9 seconds. Those considered candidates for autologous stem cell transplant (N = 26) were younger, with fewer comorbidities, better performance status, and faster performance on the Timed Up and Go test. Factors independently associated with receiving autologous stem cell transplant (N = 21) included age and IADL dependence. CONCLUSION: Impairments in geriatric domains are common in this population, even among those considered to have a good performance status. Geriatric assessment domains are associated with both transplant eligibility and receipt. J Am Geriatr Soc 67:987–991, 2019. [ABSTRACT FROM AUTHOR]

The article discusses a study focusing on myeloproliferative neoplasm (MPN) patients with splanchnic vein thrombosis (SVT) and their laboratory and molecular features. Topics discussed include the allele burden of the patients under study; the predisposition of concurrent thrombophilia to SVT; and the phenomenon of haemodilution due to portal hypertension and splenomegaly.

We previously reported that nab-paclitaxel-based induction chemotherapy ( IC) and concurrent chemoradiotherapy resulted in low relapse rates (13%) and excellent survival in head and neck squamous cell carcinoma ( HNSCC). We compare the disease-specific survival ( DSS) and overall survival ( OS) between patients given nab-paclitaxel, cisplatin, and fluorouracil with cetuximab ( APF-C) and historical controls given docetaxel, cisplatin, and fluorouracil with cetuximab ( TPF-C). Patients with locally advanced HNSCC were treated with APF-C ( n = 30) or TPF-C ( n = 38). After 3 cycles of IC, patients were scheduled to receive cisplatin concurrent with definitive radiotherapy. T and N classification and smoking history were similar between the two groups and within p16-positive and p16-negative subsets. The median duration of follow-up for living patients in the APF-C group was 43.5 (range: 30-58) months versus 52 (range: 13-84) months for TPF-C. The 2-year DSS for patients treated with APF-C was 96.7% [95% Confidence Interval ( CI): 85.2%, 99.8%] and with TPF-C was 77.6% ( CI: 62.6%, 89.7%) ( P = 0.0004). Disease progression that resulted in death was more frequent in the TPF-C group (39%) compared with the APF-C group (3%) when adjusted for competing risks of death from other causes (Gray's test, P = 0.0004). In p16 positive OPSCC, the 2-year DSS for APF-C was 100% and for TPF-C was 74.6% ( CI: 47.4%, 94.6%) ( P = 0.0019) and the 2-year OS for APF-C was 94.1% ( CI: 65.0%, 99.2%) and for TPF-C was 74.6% ( CI: 39.8%, 91.1%) ( P = 0.013). In p16 negative HNSCC, the 2-year DSS for APF-C was 91.7% ( CI: 67.6%, 99.6%) and for TPF-C was 82.6% ( CI: 64.4%, 94.8%) ( P = 0.092). A 2-year DSS and OS were significantly better with a nab-paclitaxel-based IC regimen ( APF-C) compared to a docetaxel-based IC regimen ( TPF-C) in p16-positive OPSCC. [ABSTRACT FROM AUTHOR]

Computed tomography ( CT), the standard method to assess tumor response to cetuximab in incurable squamous cell carcinoma of the head and neck ( SCCHN), performs poorly as judged by the disparity between high disease control rate (46%) and short time to progression ( TTP) (70 days). F-18 fluorodeoxyglucose positron emission tomography ( FDG- PET)/ CT is an alternative method to assess tumor response. The primary objective of this prospective trial was to evaluate the metabolic response of target lesions, assessed as the change in maximum standardized uptake value ( SUVmax) on FDG- PET/ CT before and after 8 weeks (cycle 1) of cetuximab. Secondary objectives were to compare tumor response by CT ( RECIST 1.0) and FDG- PET/ CT ( EORTC criteria) following cycle 1, and determine TTP with continued cetuximab administration in patients with disease control by CT after cycle 1 but stratified for disease control or progression by FDG- PET/ CT. Among 27 patients, the mean percent change of SUVmax of target lesions after cycle 1 was −21% (range: +72% to −81%); by FDG- PET/ CT, partial response ( PR)/stable disease ( SD) occurred in 15 patients (56%) and progression in 12 (44%), whereas by CT, PR/ SD occurred in 20 (74%) and progression in 7 (26%). FDG- PET/ CT and CT assessments were discordant in 14 patients ( P = 0.0029) and had low agreement ( κ = 0.30; 95% confidence interval [ CI]: 0.12, 0.48). With disease control by CT after cycle 1, median TTP was 166 days ( CI: 86, 217) if the FDG- PET/ CT showed disease control and 105 days ( CI: 66, 159) if the FDG- PET/ CT showed progression ( P < 0.0001). Median TTP of the seven patients whose post cycle 1 CT showed progression compared to the 12 whose FDG- PET/ CT showed progression were similar (53 [ CI: 49, 56] vs. 61 [ CI: 50, 105] days, respectively). FDG- PET/ CT may be better than CT in assessing benefit of cetuximab in incurable SCCHN. [ABSTRACT FROM AUTHOR]

Clinicopathological paradox has hampered significantly the effective assessment of the efficacy of therapeutic intervention for multiple sclerosis. Neuroimaging biomarkers of tissue injury could guide more effective treatment by accurately reflecting the underlying subclinical pathologies. Diffusion tensor imaging-derived directional diffusivity and anisotropy indices have been applied to characterize white matter disorders. However, these biomarkers are sometimes confounded by the complex pathologies seen in multiple sclerosis and its animal models. Recently, a novel technique of diffusion basis spectrum imaging has been developed to quantitatively assess axonal injury, demyelination and inflammation in a mouse model of inflammatory demyelination. Lenaldekar, which inhibits T-cell expansion in a non-cytolytic manner, has been shown to suppress relapses and preserve white matter integrity in mice with experimental autoimmune encephalomyelitis. In this study, relapsing-remitting experimental autoimmune encephalomyelitis was induced through active immunization of SJL/J mice with a myelin proteolipid protein peptide. The therapeutic efficacy of Lenaldekar treatment was evaluated via daily clinical score, cross-sectional ex vivo diffusion basis spectrum imaging examination and histological analysis. Lenaldekar greatly reduced relapse severity and protected white matter integrity in these experimental autoimmune encephalomyelitis mice. Diffusion basis spectrum imaging-derived axial diffusivity, radial diffusivity and restricted diffusion tensor fraction accurately reflected axonal injury, myelin integrity and inflammation-associated cellularity change, respectively. These results support the potential use of diffusion basis spectrum imaging as an effective outcome measure for preclinical drug evaluation. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Manganese-enhanced MRI (MEMRI) with topical loading of MnCl2 provides optic nerve enhancement comparable to that seen by intravitreal injection. However, the impact of this novel and non-invasive Mn2+ loading method on visual function requires further assessments. The objective of this study is to determine the optimal topical Mn2+ loading dosage for MEMRI and to assess visual function after MnCl2 loading. Intravitreal administration was performed to compare the two approaches of MnCl2 loading. Twenty-four hours after topical loading of 0, 0.5, 0.75, and 1 M MnCl2, T1-weighted, T2-weighted, diffusion tensor imaging and visual acuity (VA) assessments were performed to determine the best topical loading dosage for MEMRI measurements and to assess the integrity of retinas and optic nerves. Mice were perfusion fixed immediately after in vivo experiments for hematoxylin and eosin and immunohistochemistry staining. Topical loading of 1 M MnCl2 damaged the retinal photoreceptor layer with no detectable damage to retina ganglion cell layers or prechiasmatic optic nerves. For the topical loading, 0.75 M MnCl2 was required to see sufficient enhancement of the optic nerve. At this concentration the visual function was significantly affected, followed by a slow recovery. Intravitreal injection (0.25 μL of 0.2 M MnCl2) slightly affected VA, with full recovery a day later. To conclude, intravitreal MnCl2injection provides more reproducible results with less adverse side-effects than topical loading. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Fingolimod (FTY720) is an orally available sphingosine-1-phosphate (S1P) receptor modulator reducing relapse frequency in patients with relapsing-remitting multiple sclerosis (RRMS). In addition to immunosuppression, neuronal protection by FTY720 has also been suggested, but remains controversial. Axial and radial diffusivities derived from in vivo diffusion tensor imaging (DTI) were employed as noninvasive biomarkers of axonal injury and demyelination to assess axonal protection by FTY720 in experimental autoimmune encephalomyelitis (EAE) mice. EAE was induced through active immunization of C57BL/6 mice using myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55). We evaluated both the prophylactic and therapeutic treatment effect of FTY720 at doses of 3 and 10 mg/kg on EAE mice by daily clinical scoring and end-point in vivo DTI. Prophylactic administration of FTY720 suppressed the disease onset and prevented axon and myelin damage when compared with EAE mice without treatment. Therapeutic treatment by FTY720 did not prevent EAE onset, but reduced disease severity, improving axial and radial diffusivity towards the control values without statistical significance. Consistent with previous findings, in vivo DTI-derived axial and radial diffusivity correlated with clinical scores in EAE mice. The results support the use of in vivo DTI as an effective outcome measure for preclinical drug development. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND: Complete response (CR) at the primary tumor site as assessed by clinical examination following induction chemotherapy with PF (cis platin and 5- fluorouracil [5-FU]) is a favorable predictive factor for overall survival and disease control in patients with locally advanced squamous cell carcinoma of the head and neck. In most series, the rate of CR at the primary site after induction PF was 20% to 30%. This study evaluated the efficacy and feasibility of induction n ab-paclitaxel and cetuximab given with PF (ACPF) followed by definitive chemoradiation (CRT) in a phase 2 trial. METHODS: Patients with squamous cell carcinoma of the head and neck were treated with ACPF ( nab-paclitaxel 100 mg/m2/week; cetuximab 250 mg/m2/week; cisplatin 75 mg/m2 on day 1; 5-FU 750 mg/m2/day on days 1 through 3) every 21 days for 3 cycles followed by CRT (cisplatin 100 mg/m2 on days 1, 22, and 43 of radiation therapy [RT]). CR at the primary tumor site after 2 cycles of ACPF was the primary endpoint. RESULTS: Thirty patients were enrolled, of which 22 (73%) had large (T3/T4) primary tumors. The CR rate at the primary tumor site after 2 cycles of ACPF was 53% and the overall response rate was 100%. Twenty-nine (96%) patients completed 3 cycles of ACPF, 26 (90%) completed definitive RT per protocol, and 22 of the 27 evaluable patients (81%) received > 2 of the 3 planned doses of cisplatin with RT. The estimated 2-year overall and progression-free survival rates were 84% and 65%, respectively. CONCLUSIONS: Induction ACPF resulted in a high CR rate (53%) at the primary tumor site even in large tumors and did not adversely affect delivery of definitive CRT. Further investigation of ACPF is warranted. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background. Current literature reports widely different rates of distant metastasis at presentation for squamous cell carcinoma of the head and neck (SCCHN). We used the Surveillance Epidemiology and End Results (SEER) database to determine the rate of and risk factors for distant metastasis. Methods. We identified patients with SCCHN diagnosed between 1988 and 2003. The rate of distant metastasis was determined and then stratified by tumor site, size, and nodal status. To evaluate the contribution of each individual factor, both univariate and multivariate analyses were performed. Results. Among 73,247 patients identified, 2066 patients (2.82%, 95% confidence interval [CI] 2.70-2.94%) had distant metastasis. Independent risk factors for distant metastasis included primary site, nodal status, tumor size, age, and race. Conclusions. In SCCHN, there is a relationship between the risk of distant metastasis and tumor site, size, and nodal status. This information can be used to guide the evaluation and treatment of SCCHN. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to develop a Cancer Pain Inventory (CPI) that measures cancer patients' beliefs and concerns about pain. This paper describes development and pilot testing of a preliminary version of the CPI and describes its psychometric properties including its reliability and validity relative to established pain measures. Methods: Subjects were recruited from inpatient and outpatient oncology services of an NCI-designated comprehensive cancer center. Participants completed the 50 potential CPI items and these standard measures—Orientation-Memory-Concentration Test, Survey of Pain Attitudes, Brief Pain Inventory, Pain Disability Index, and Center for Epidemiological Studies—Depression Scale. The magnitude and significance of associations between the CPI and the other measures were examined. Results: Of 366 patients who were eligible and agreed to participate in the study, 262 completed the questionnaires. Principal components analyses were used to select items most appropriate for retention in the preliminary version of the CPI and to describe its factor structure. Based on the content of items that loaded on each factor, the five factors were labeled as Catastrophizing, Interference with Functioning, Stoicism, Social Aspects, and Concerns about Pain Medication. Correlations between the CPI and other measures supported construct validity of the five CPI factors. Conclusions: The results supported the validity of the CPI as a measure of five constructs relevant to the experience of pain in the cancer setting. The results also underscored the presence of unique features of cancer-related pain that clearly differ from commonly recognized dimensions of chronic, non-cancer-related pain. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In all, 20% of fine-needle aspiration (FNA) biopsies of thyroid nodules have an indeterminate diagnosis; of these, 80% are found to be benign after thyroidectomy. Some previous reports indicate that positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) imaging may predict malignancy status. We now report results on the first 51 patients in the largest prospective study of FDG-PET in patients with an indeterminate thyroid nodule FNA. Eligible patients had a dominant thyroid nodule that was palpable or ≥1 cm in greatest dimension as seen by ultrasonography, and indeterminate histology of the FNA biopsy specimen. Participants underwent preoperative neck FDG-PET alone or FDG-PET with computed tomography (FDG-PET/CT). Images were evaluated qualitatively and semiquantitatively using the maximum standardized uptake value (SUVmax). Final diagnosis was determined by histopathologic analysis after thyroidectomy. Descriptive statistical analysis was performed. A total of 51 patients underwent preoperative FDG-PET or FDG-PET/CT. Studies without focally increased uptake localized to the lesion were considered negative. For all lesions (10 malignant, 41 benign), the sensitivity, specificity, positive-predictive value (PPV), and negative-predictive value (NPV) were 80%, 61%, 33%, and 93%, respectively. Postoperatively, two malignant and six benign lesions were found to be <1 cm by pathology examination; one lesion was not measured. When these lesions were excluded, the sensitivity, specificity, PPV, and NPV were 100%, 59%, 36%, and 100%, respectively. Based on these preliminary data, FDG-PET may have a role in excluding malignancy in thyroid nodules with an indeterminate FNA biopsy. This finding justifies ongoing accrual to our target population of 125 participants. [ABSTRACT FROM AUTHOR]

Objectives. To determine the influence of trait anxiety on patient reports of health- related quality of life (HRQoL) and post-traumatic stress symptoms (PTSS) in a sample of rectal cancer survivors. Design. Eighty patients who had been diagnosed with rectal cancer were assessed at two points in time in a longitudinal study. Methods. At Time I, soon after initial treatment, participants completed the State- Trait Anxiety Inventory and the Temperament and Character Inventory Harm Avoidance scale, which were combined into a composite measure of trait anxiety. At Time 2, 2-5 years following Time I, participants were assessed for HRQoL using the Functional Assessment of Cancer Therapy-Colorectal scale (FACT-C) and for PTSS using the Impact of Event Scale-Revised (IES-R). Results. HRQoL and PTSS were generally favourable on average, although many of the patients reported faring poorly. Higher levels of trait anxiety were predictive of poorer scores on all of the FACT-C and the IES-R total and subscale measures. More severe faecal incontinence was associated with poorer scores on the FACT Emotional well-being subscale, the FACT-Colorectal Cancer Scale, and all of the IES-R scales. Males were more likely than females to have poorer scores on the FACT Social well- being subscale, and those patients who were further out from active treatment had more favourable scores on the FACT-Colorectal Cancer Scale. The presence of a colostomy did not impact HRQoL or PTSS. Conclusion. Trait anxiety had a significant influence on HRQoL and PTSS several years following diagnosis and treatment of rectal cancer. [ABSTRACT FROM AUTHOR]

We examined in vivo measurements of directional diffusivity derived from diffusion tensor imaging (DTI) to study the evolution of ventrolateral white matter (VWM) changes following contusive spinal cord injury (SCI) in C57BL/6 mice at 1, 3, 7, and 14 days postinjury. Relative anisotropy maps provided excellent gray matter (GM)/white matter (WM) contrast for characterization of evolving WM injury at all time points. Longitudinal DTI measurements clearly demonstrated rostral-caudal injury asymmetry. Axial diffusivity provided a sensitive, noninvasive measure of axonal integrity within the injury epicenter and at remote levels. Quantitative measurements of axial and radial diffusivities in VWM showed a trend of acute primary axonal injury followed by delayed, subacute myelin damage at the impact site, with good histological correlation. Magn Reson Med 58:253-260, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

It has been demonstrated previously that water diffusion anisotropy in vivo is equivalent to that observed ex vivo after perfusion fixation in the mouse brain. This finding supports the practice of ex vivo diffusion tensor imaging (DTI) measurement on perfusion-fixed tissues. However, the validity of extrapolating ex vivo DTI measurements from immersion-fixed autopsy specimens to the in vivo state is questionable because of variable postmortem delays often encountered before fixation. In this study, we investigated the effect of postmortem delay on the water diffusion anisotropy of ventrolateral spinal cord white matter from mice. Mouse spinal cords, each from the same animal, were examined using DTI in vivo, in situ after death before fixation, and ex vivo immersion fixed 10 h after death. Our results suggest that diffusion anisotropy in mouse spinal cord is preserved up to 10 h after death. Regional characteristics of diffusion anisotropy in mouse spinal cord white matter are equivalent in vivo, in situ after death (up to 10 h before fixation), and ex vivo 15 weeks after immersion fixation. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Previously, we tested the prediction that axonal damage results in decreased axial diffusivity (λ∥) while demyelination leads to increased radial diffusivity (λ⟂). Cuprizone treatment of C57BL/6 mice was a highly reproducible model of CNS white matter demyelination and remyelination affecting the corpus callosum (CC). In the present study, six C57BL/6 male mice were fed 0.2% cuprizone for 12 weeks followed by 12 weeks of recovery on normal chow. The control mice were fed normal chow and imaged in parallel. Biweekly in vivo DTI examinations showed transient decrease of λ∥ in CC at 2-6 weeks of cuprizone treatment. Immunostaining for nonphosphorylated neurofilaments demonstrated corresponding axonal damage at 4 weeks of treatment. Significant demyelination was evident from loss of Luxol fast blue staining at 6-12 weeks of cuprizone ingestion and was paralleled by increased λ⟂ values, followed by partial normalization during the remyelination phase. The sensitivity of λ⟂ to detect demyelination may be modulated in the presence of axonal damage during the early stage of demyelination at 4 weeks of cuprizone treatment. Our results suggest that λ∥ and λ⟂ may be useful in vivo surrogate markers of axonal and myelin damage in mouse CNS white matter. Magn Reson Med, 2006. Published 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND: It was hypothesized that transfusion of two granulocyte–colony-stimulating factor (G-CSF)-mobilized prophylactic granulocyte components into allogeneic peripheral blood progenitor cell (PBPC) transplant patients during the regimen-related neutropenic interval would result in clinical benefit. STUDY DESIGN AND METHODS: HLA-matched sibling PBPC donors (n = 151) were biologically randomized based on ABO mismatch to donate granulocyte components (Cohort G) or not donate granulocytes (control group, Cohort C). ABO-matched donors who did not meet other study-specific criteria were reassigned to Cohort C. RESULTS: Feasibility, defined as the proportion of ABO-matched donors who underwent granulocyte collections, was 42 percent (53 of 125). The percentage of patients who developed fever during the initial hospitalization was greater in Cohort C versus Cohort G (82.7% vs. 64.2%; p = 0.03). In the interval from when granulocyte transfusions were initially given in Cohort G (Day +3 or Day +5) until neutrophil engraftment, the number of febrile days was less in Cohort G versus Cohort C (median, 0 vs. 1; Mann-Whitney p = 0.003). The median number of days of intravenous antibiotics given during the initial hospitalization was less in Cohort G versus Cohort C (9 vs. 11; Mann-Whitney p = 0.03), a difference accounted for in the interval from Day +3 or Day +5 to neutrophil recovery. There was no significant difference in length of the initial hospital stay, acute graft-versus-host disease rates, or 100-day survival between the two cohorts. CONCLUSION: This prospective study demonstrates a modest, but significant, benefit of G-CSF–mobilized HLA-matched prophylactic granulocyte transfusions in neutropenic allogeneic PBPC recipients. [ABSTRACT FROM AUTHOR]

This research investigated psychological characteristics associated with delay in seeking help for symptoms of rectal cancer. Sixty nine subjects reconstructed pivotal events beginning with symptom onset and ending with medical consultation, and completed the Temperament and Character Inventory (TCI) and the State-Trait Anxiety Inventory (STAI). The mean delay time was around 6 months, with about 1 out of 6 subjects waiting one year or more. Subjects estimated the lengths of two sequential segments of total time to consultation: (1) Symptom Appraisal time (from symptom onset to recognition of possible seriousness), and (2) Action Appraisal time (from recognition of seriousness to medical consultation). Symptom Appraisal time accounted for over two-thirds of total time and was associated with low scores on the TCI Harm Avoidance scale (TCI-HA), indicating dispositional insensitivity to threat, and marginally associated with less education and younger age. Action Appraisal time was not associated with any demographic or psychological variables. Low TCI-HA scores were also associated with lower likelihood of previous cancer screening, and with better judgments of premorbid health. Low STAI Trait scores were associated with better judgments of premorbid health and fewer doctor visits. Results are discussed regarding the importance of understanding dispositional characteristics related to health behavior. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]