The diagnostic and therapeutic impact of MRI: an observational multi-centre study

AIM: To provide information about the diagnostic and therapeutic impact of magnetic resonance imaging (MRI) and to compare the findings across diagnostic groups. MATERIALS AND METHODS: A prospective, observational study of 2017 consecutive referrals for MRI of the head, spine or knee at four imaging centres. Clinicians completed questionnaires before MRI stating initial diagnoses, diagnostic confidence and treatment plans. After imaging, a second questionnaire evaluated clinicians' revised diagnosis and treatment plans in the light of imaging findings. Patients were grouped into nine diagnostic categories for analysis. Comparison between pre- and post-imaging was used to assess the diagnostic and therapeutic impact of MRI. RESULTS: In seven of nine diagnostic groups MRI findings were associated with a diagnostic impact. Diagnoses were revised or discarded following normal MR findings and diagnostic confidence was increased by confirmative MR findings. There was no statistically significant diagnostic impact for suspected pituitary or cerebello-pontine angle lesions. In five of nine diagnostic groups (knee meniscus, knee ligament, multiple sclerosis, lumbar and cervical spine) MRI findings had a clear impact on treatment plans. CONCLUSION: This study demonstrates that in most diagnostic categories, MRI influences diagnosis and treatment. However, experimental studies are needed to prove that these diagnostic and therapeutic impacts lead to improved health.Hollingworth (2000). Clinical Radiology55, 825-831.     

Antineoplastic effects of partially HLA-matched irradiated blood mononuclear cells in patients with renal cell carcinoma.

PURPOSE: Vaccines, cytokines, and other biologic-based therapies are being developed as antineoplastic agents. Many of these agents are designed to induce an autologous immune response directed against the malignancy. In contrast, hematopoietic stem-cell transplantation is being developed as a form of allogeneic immunotherapy. This study tests the tolerance and antineoplastic activity of sequential infusions of partially HLA-matched allogeneic blood mononuclear cells (obtained from relatives) when administered outside of the context of a hematopoietic stem-cell transplantation. The cells are irradiated to prevent graft-versus-host disease. PATIENTS AND METHODS: Fifteen patients with relapsed or refractory malignancies for which no standard therapy was available were enrolled onto a clinical trial designed to assess the tolerability and antineoplastic effects of irradiated partially HLA-matched blood mononuclear cells obtained from relatives. RESULTS: There was disease regression in three patients with metastatic renal cell carcinoma during treatment. There was disease progression in six patients with metastatic renal cell carcinoma and two patients with metastatic melanoma during treatment. There was no change in disease state in several other patients. CONCLUSION: Irradiated allogeneic blood mononuclear cells administered outside the context of hematopoietic stem-cell transplantation may induce disease responses in patients with relapsed or refractory malignancies. Transfusion of irradiated allogeneic blood mononuclear cells should be developed further as a novel therapeutic antineoplastic approach.     

Stapedectomy Training With the Carbon Dioxide Laser

All primary carbon dioxide (CO₂) laser stapedectomies supervised by the senior author since 1986 were retrospectively reviewed and reported according to 1995 American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing guidelines. Sixty-three cases had more than 6 weeks of follow-up with an average residual gap of 6.49 dB (SD = 5.55 dB) and an 89% success rate. Thirty cases had more than 1 year of follow-up with the average hearing result of 6.58 dB (SD = 5.93 dB) and an 87% success rate. In 11 cases, 14 operative problems or complications occurred. Suctioning the vestibule occurred in five cases. Because suction is required to evacuate laser smoke, these cases are attributed to the laser. One of these patients had delayed sensorineural hearing loss. One patient had profound delayed sensorineural hearing loss as a result of granuloma formation. These were the only major complications. The laser is a tool that gives reproducible technique and good success rates.     

Alcohol intake is associated with altered pulmonary function.

Little is known about the effect of moderate alcohol intake on lung function in the general population. Because moderate alcohol intake appears to reduce cardiovascular disease risk, we hypothesized that moderate alcohol intake is associated with better pulmonary function. To test this hypothesis, we examined the association between alcohol intake and pulmonary function, measured by spirometry, in a representative sample of U.S. adults who participated in the Third National Health and Nutrition Examination Survey. A stratified multistage clustered probability design was used to select a population-based sample. Data analyzed included alcohol intake, smoking status, education, body mass, sex, age, race, diabetes status, and CHF status. The Third National Health and Nutrition Examination Survey was conducted from 1988 to 1994 by the National Center for Health Statistics of the Centers for Disease Control and Prevention, Atlanta, GA. We analyzed data from 15,294 study participants who completed extensive questionnaires in the household and a comprehensive physical examination, including pulmonary function testing, either in the household or at a specially equipped mobile examination center. Low-to-moderate alcohol intake was not associated with reduced odds of obstructive lung function. In fact, increased odds for obstructive lung pattern were observed only in former heavy drinkers. In contrast, low-to-moderate alcohol intake was associated with better forced vital capacity and forced exhaled volume in 1s in the absence of obstruction, consistent with reduced odds for lung restriction. Using a logistic regression model, we found that individuals reporting alcohol consumption had a lower risk of lung restriction both before and after adjusting for confounding factors including smoking (P< or =.001). Alcohol intake-related reduced risk for restriction was associated with lower risk of CHF, diabetes, obesity, and lower markers of inflammation (white blood cell, fibrinogen, and C-reactive protein) consistent with less lung congestion, external restriction, and/or lung inflammation. Our analyses indicate that alcohol consumption, even at very modest intake levels, is associated with less lung restriction.     

Development of the multi-attribute Pediatric Asthma Health Outcome Measure (PAHOM).

OBJECTIVE: To develop a multi-attribute outcome measure for children with asthma that allows for the calculation of quality-adjusted life years in cost-effectiveness studies and can also be used to assign preference weights to asthma-symptom-free days. STUDY DESIGN: A literature review and two interviewer-administered surveys. SETTING: Homes or community centers of participants in Seattle, United States. MAIN MEASURE: Visual analog scale (VAS), standard gamble (SG), and relative risk attitude equation techniques were used to estimate two sets of preference weights for 10 health states. The PAHOM was used to record health states of pediatric asthma patients. RESULTS: A total of 94 subjects provided complete responses without any illogical ratings to VAS questions and 101 provided the same to SG questions. The VAS preference weights of the health states range from a maximum of 1 for perfect health to a minimum of 0.03 for severe asthma symptoms, emotional problems, and activity limitations. Those based on the relative risk attitude equation constructed with both VAS and SG preference weights range from 1 to 0.06. The mean PAHOM scores of pediatric asthma patients based on VAS and converted SG preference weights were 0.70 and 0.83, respectively. CONCLUSIONS: The PAHOM calendar can be used to identify asthma patients' health outcomes, to calculate the preference weights of asthma patients' health states, and to estimate the number of symptom-free days. These factors make the PAHOM a promising instrument for use in effectiveness and cost-effectiveness studies in children with asthma.     

Sensory stimulation increases cortical expression of the fragile X mental retardation protein in vivo

Fragile X syndrome is a common cause of mental retardation that results from the absence of the fragile X mental retardation protein (FMRP), an RNA binding protein whose function remains unclear. Recent in vitro work has demonstrated that the protein is translated near the synapse in an activity dependent manner [33]. We therefore asked whether expression of FMRP might be altered by neuronal activity in vivo. Using immunoblots of different sub-cellular fractions of the rat somatosensory cortex, we show that the levels of FMRP increase significantly following unilateral whisker stimulation, a model of experience dependent plasticity. This increase is greatest between 2 and 8 h after the stimulus and is seen in both a synaptosomal fraction as well as a sub-cellular fraction enriched for polyribosomal complexes. In contrast, detectable levels of FMRP within the somatosensory cortex show either a decrease or no change after a kainic acid induced seizure compared to water treated controls. Our findings demonstrate that FMRP expression levels are modulated in vivo in response to neuronal activity and suggest a role for FMRP in activity dependent plasticity.     

Molecular mechanisms of resistance to therapies targeting the epidermal growth factor receptor.

Targeted therapies that inhibit the activity of tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR) have shown activity against solid malignancies when used as single agents or in combination with chemotherapy. Although anti-EGFR therapies are active in some patients, eventually disease in nearly all patients will become refractory to therapy. Therefore, a better understanding of the mechanisms of resistance to anti-EGFR therapies is critical to further improve the efficacy of this class of agents. Mechanisms that mediate resistance to anti-EGFR therapies include the presence of redundant tyrosine kinase receptors, increased angiogenesis, and the constitutive activation of downstream mediators. Two recent landmark publications have also shown that specific mutations in the kinase domain of EGFR in some lung carcinomas are associated with markedly improved response rates to an EGFR tyrosine kinase inhibitor. Mutations in the EGFR receptor seem to play a significant role in determining the sensitivity of tumor cells to EGFR inhibitor therapy by altering the conformation and activity of the receptor. As the field of molecular therapeutics continues to evolve, a comprehensive understanding of resistance mechanisms will ultimately lead to refinements in our regimens to provide better care for patients with cancer.     

Randomized trial of amifostine in locally advanced non-small-cell lung cancer patients receiving chemotherapy and hyperfractionated radiation: radiation therapy oncology group trial 98-01.

PURPOSE: To test the ability of the cytoprotectant, amifostine, to reduce chemoradiotherapy-induced esophagitis and evaluate its influence on quality of life (QOL) and swallowing symptoms. PATIENTS AND METHODS: A total of 243 patients with stage II to IIIA/B non-small-cell lung cancer received induction paclitaxel 225 mg/m(2) intravenously (IV) days 1 and 22 and carboplatin area under the curve (AUC) days 1 and 22, followed by concurrent weekly paclitaxel (50 mg/m(2) IV) and carboplatin (AUC 2), and hyperfractionated radiation therapy (69.6 Gy at 1.2 Gy bid). Patients were randomly assigned at registration to amifostine (AM) 500 mg IV four times per week or no AM during chemoradiotherapy. Beyond standard toxicity end points, physician dysphagia logs (PDLs), daily patient swallowing diaries, and QOL (EORTC QLQ-C30/LC-13) were also collected. Swallowing AUC analyses were calculated from patient diaries and PDLs. RESULTS: A total of 120 patients were randomly assigned to receive AM, and 122, to receive no AM (one patient was ineligible); 72% received AM per protocol or with a minor deviation. AM was associated with higher rates of acute nausea (P = .03), vomiting (P = .007), cardiovascular toxicity (P = .0001), and infection or febrile neutropenia (P = .03). The rate of >/= grade 3 esophagitis was 30% with AM versus 34% without AM (P = .9). Patient diaries demonstrated lower swallowing dysfunction AUC with amifostine (z test P = .025). QOL was not significantly different between the two arms, except for pain, which showed more clinically meaningful improvement and less deterioration at 6 weeks follow-up (v pretreatment) in the AM arm (P = .003). The median survival rates for both arms were comparable (AM, 17.3 v no AM, 17.9 months; P = .87). CONCLUSION: AM did not significantly reduce esophagitis >/= grade 3 in patients receiving hyperfractionated radiation and chemotherapy. However, patient self-assessments suggested a possible advantage to AM that is being explored with modified dosing route strategies.     

Multimorbidity and healthcare utilization among early survivors of pediatric cancer

Early survivors of pediatric cancer are at increased risk of experiencing chronic conditions; however, little is known about the morbidity burden in this population. In this observational cohort study of commercially insured pediatric cancer survivors in the United States (2009–2014), we find that 22.5% of survivors had one chronic condition, and 36.3% had multiple. Compared with survivors without chronic conditions, the presence of multiple conditions significantly increased the odds of an emergency department visit by 70% (odds ratios [OR], 1.7; 95% confidence interval [CI], 1.4–2.1) and of a hospitalization almost four‐fold (OR, 3.8; 95% CI], 2.5–5.5). Findings are important for informing pediatric survivorship care plans in the years following completion of therapy.