Showing papers by "Mayo Clinic published in 2006"
McGill University1, New York University2, Mayo Clinic3, French Institute of Health and Medical Research4, Federal Institute for Drugs and Medical Devices5, University of New South Wales6, Rush University Medical Center7, University of California, Los Angeles8, Vancouver Hospital and Health Sciences Centre9, University of Pittsburgh10, Ludwig Maximilian University of Munich11, VU University Medical Center12, Women's College, Kolkata13, Case Western Reserve University14, Karolinska Institutet15
TL;DR: Mild cognitive impairment can be regarded as a risk state for dementia, and its identification could lead to secondary prevention by controlling risk factors such as systolic hypertension.
3,962 citations
TL;DR: The prevalence of heart failure with preserved ejection fraction increased over a 15-year period, while the rate of death from this disorder remained unchanged, and trends underscore the importance of this growing public health problem.
Abstract: Background The prevalence of heart failure with preserved ejection fraction may be changing as a result of changes in population demographics and in the prevalence and treatment of risk factors for heart failure. Changes in the prevalence of heart failure with preserved ejection fraction may contribute to changes in the natural history of heart failure. We performed a study to define secular trends in the prevalence of heart failure with preserved ejection fraction among patients at a single institution over a 15-year period. Methods We studied all consecutive patients hospitalized with decompensated heart failure at Mayo Clinic Hospitals in Olmsted County, Minnesota, from 1987 through 2001. We classified patients as having either preserved or reduced ejection fraction. The patients were also classified as community patients (Olmsted County residents) or referral patients. Secular trends in the type of heart failure, associated cardiovascular disease, and survival were defined. Results A total of 6076 patients with heart failure were discharged over the 15-year period; data on ejection fraction were available for 4596 of these patients (76 percent). Of these, 53 percent had a reduced ejection fraction and 47 percent had a preserved ejection fraction. The proportion of patients with the diagnosis of heart failure with preserved ejection fraction increased over time and was significantly higher among community patients than among referral patients (55 percent vs. 45 percent). The prevalence rates of hypertension, atrial fibrillation, and diabetes among patients with heart failure increased significantly over time. Survival was slightly better among patients with preserved ejection fraction (adjusted hazard ratio for death, 0.96; P=0.01). Survival improved over time for those with reduced ejection fraction but not for those with preserved ejection fraction. Conclusions The prevalence of heart failure with preserved ejection fraction increased over a 15-year period, while the rate of death from this disorder remained unchanged. These trends underscore the importance of this growing public health problem.
3,823 citations
TL;DR: In this paper, the authors assess the prevalence and effect of valve disease on overall survival in the general population and find that moderate or severe valve disease is common in this population and increase with age.
3,468 citations
TL;DR: Revised diagnostic criteria for definite neuromyelitis optica (NMO) that require optic neuritis, myelitis, and at least two of three supportive criteria: MRI evidence of a contiguous spinal cord lesion 3 or more segments in length, onset brain MRI nondiagnostic for multiple sclerosis, or NMO-IgG seropositivity.
Abstract: Background: The authors previously proposed diagnostic criteria for neuromyelitis optica (NMO) that facilitate its distinction from prototypic multiple sclerosis (MS) However, some patients with otherwise typical NMO have additional symptoms not attributable to optic nerve or spinal cord inflammation or have MS-like brain MRI lesions Furthermore, some patients are misclassified as NMO by the authors’ earlier proposed criteria despite having a subsequent course indistinguishable from prototypic MS A serum autoantibody marker, NMO-IgG, is highly specific for NMO The authors propose revised NMO diagnostic criteria that incorporate NMO-IgG status Methods: Using final clinical diagnosis (NMO or MS) as the reference standard, the authors calculated sensitivity and specificity for each criterion and various combinations using a sample of 96 patients with NMO and 33 with MS The authors used likelihood ratios and logistic regression analysis to develop the most practical and informative diagnostic model Results: Fourteen patients with NMO (146%) had extra-optic-spinal CNS symptoms NMO-IgG seropositivity was 76% sensitive and 94% specific for NMO The best diagnostic combination was 99% sensitive and 90% specific for NMO and consisted of at least two of three elements: longitudinally extensive cord lesion, onset brain MRI nondiagnostic for MS, or NMO-IgG seropositivity Conclusions: The authors propose revised diagnostic criteria for definite neuromyelitis optica (NMO) that require optic neuritis, myelitis, and at least two of three supportive criteria: MRI evidence of a contiguous spinal cord lesion 3 or more segments in length, onset brain MRI nondiagnostic for multiple sclerosis, or NMO-IgG seropositivity CNS involvement beyond the optic nerves and spinal cord is compatible with NMO
2,442 citations
TL;DR: The age-adjusted incidence of AF increased significantly in Olmsted County during 1980 to 2000 and the projected number of persons with AF for the United States will exceed 10 million by 2050, underscoring the urgent need for primary prevention strategies against AF development.
Abstract: Background— Limited data exist on trends in incidence of atrial fibrillation (AF). We assessed the community-based trends in AF incidence for 1980 to 2000 and provided prevalence projections to 2050. Methods and Results— The adult residents of Olmsted County, Minnesota, who had ECG-confirmed first AF in the period 1980 to 2000 (n=4618) were identified. Trends in age-adjusted incidence were determined and used to construct model-based prevalence estimates. The age- and sex-adjusted incidence of AF per 1000 person-years was 3.04 (95% CI, 2.78 to 3.31) in 1980 and 3.68 (95% CI, 3.42 to 3.95) in 2000. According to Poisson regression with adjustment for age and sex, incidence of AF increased significantly (P=0.014), with a relative increase of 12.6% (95% CI, 2.1 to 23.1) over 21 years. The increase in age-adjusted AF incidence did not differ between men and women (P=0.84). According to the US population projections by the US Census Bureau, the number of persons with AF is projected to be 12.1 million by 2050, ...
2,430 citations
TL;DR: There is evidence of an increased risk of serious infections and a dose-dependent increasedrisk of malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody therapy.
Abstract: ContextTumor necrosis factor (TNF) plays an important role in host defense and tumor growth control. Therefore, anti-TNF antibody therapies may increase the risk of serious infections and malignancies.ObjectiveTo assess the extent to which anti-TNF antibody therapies may increase the risk of serious infections and malignancies in patients with rheumatoid arthritis by performing a meta-analysis to derive estimates of sparse harmful events occurring in randomized trials of anti-TNF therapy.Data SourcesA systematic literature search of EMBASE, MEDLINE, Cochrane Library, and electronic abstract databases of the annual scientific meetings of both the European League Against Rheumatism and the American College of Rheumatology was conducted through December 2005. This search was complemented with interviews of the manufacturers of the 2 licensed anti-TNF antibodies.Study SelectionWe included randomized, placebo-controlled trials of the 2 licensed anti-TNF antibodies (infliximab and adalimumab) used for 12 weeks or more in patients with rheumatoid arthritis. Nine trials met our inclusion criteria, including 3493 patients who received anti-TNF antibody treatment and 1512 patients who received placebo.Data ExtractionData on study characteristics to assess study quality and intention-to-treat data for serious infections and malignancies were abstracted. Published information from the trials was supplemented by direct contact between principal investigators and industry sponsors.Data SynthesisWe calculated a pooled odds ratio (Mantel-Haenszel methods with a continuity correction designed for sparse data) for malignancies and serious infections (infection that requires antimicrobial therapy and/or hospitalization) in anti-TNF–treated patients vs placebo patients. We estimated effects for high and low doses separately. The pooled odds ratio for malignancy was 3.3 (95% confidence interval [CI], 1.2-9.1) and for serious infection was 2.0 (95% CI, 1.3-3.1). Malignancies were significantly more common in patients treated with higher doses compared with patients who received lower doses of anti-TNF antibodies. For patients treated with anti-TNF antibodies in the included trials, the number needed to harm was 154 (95% CI, 91-500) for 1 additional malignancy within a treatment period of 6 to 12 months. For serious infections, the number needed to harm was 59 (95% CI, 39-125) within a treatment period of 3 to 12 months.ConclusionsThere is evidence of an increased risk of serious infections and a dose-dependent increased risk of malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody therapy. The formal meta-analysis with pooled sparse adverse events data from randomized controlled trials serves as a tool to assess harmful drug effects.
2,414 citations
Cedars-Sinai Medical Center1, University of Salamanca2, University of Arkansas for Medical Sciences3, Mayo Clinic4, Alexandra Hospital5, Lund University6, Karolinska Institutet7, Ankara University8, Washington University in St. Louis9, Cross Cancer Institute10, University of Turin11, Royal Prince Alfred Hospital12, University of Texas MD Anderson Cancer Center13, University of Pavia14, Harvard University15, University of Bologna16, The Royal Marsden NHS Foundation Trust17
TL;DR: The European Group for Blood and Bone Marrow Transplant/International Bone Marrows Transplant Registry criteria have been expanded, clarified and updated to provide a new comprehensive evaluation system to adequately assess clinical outcomes in myeloma.
Abstract: New uniform response criteria are required to adequately assess clinical outcomes in myeloma. The European Group for Blood and Bone Marrow Transplant/International Bone Marrow Transplant Registry criteria have been expanded, clarified and updated to provide a new comprehensive evaluation system. Categories for stringent complete response and very good partial response are added. The serum free light-chain assay is included to allow evaluation of patients with oligo-secretory disease. Inconsistencies in prior criteria are clarified making confirmation of response and disease progression easier to perform. Emphasis is placed upon time to event and duration of response as critical end points. The requirements necessary to use overall survival duration as the ultimate end point are discussed. It is anticipated that the International Response Criteria for multiple myeloma will be widely used in future clinical trials of myeloma.
2,411 citations
Johns Hopkins University School of Medicine1, University of Michigan2, Anschutz Medical Campus3, Ohio State University4, Boston Medical Center5, University of Pennsylvania6, University of Florida7, Mayo Clinic8, University of Texas MD Anderson Cancer Center9, Memorial Sloan Kettering Cancer Center10
2,086 citations
TL;DR: The studies suggest a high prevalence of depression and anxiety among medical students, with levels of overall psychological distress consistently higher than in the general population and age-matched peers by the later years of training.
Abstract: PurposeTo systematically review articles reporting on depression, anxiety, and burnout among U.S. and Canadian medical students.MethodMedline and PubMed were searched to identify peer-reviewed English-language studies published between January 1980 and May 2005 reporting on depression, anxie
2,079 citations
TL;DR: Ovarian-type stroma has been proposed as a requisite to distinguish MCN from IPMN, and some other distinct features to characterize IPMN and MCN have been identified, but there remain ambiguities between the two diseases.
1,912 citations
TL;DR: A systematic, stepwise screen of 195 CpG island methylation markers using MethyLight technology found that CIMP-positive (CIMP+) tumors convincingly represent a distinct subset, encompassing almost all cases of tumors with BRAFmutation (odds ratio = 203).
Abstract: Aberrant DNA methylation of CpG islands has been widely observed in human colorectal tumors and is associated with gene silencing when it occurs in promoter areas. A subset of colorectal tumors has an exceptionally high frequency of methylation of some CpG islands, leading to the suggestion of a distinct trait referred to as 'CpG island methylator phenotype', or 'CIMP'. However, the existence of CIMP has been challenged. To resolve this continuing controversy, we conducted a systematic, stepwise screen of 195 CpG island methylation markers using MethyLight technology, involving 295 primary human colorectal tumors and 16,785 separate quantitative analyses. We found that CIMP-positive (CIMP+) tumors convincingly represent a distinct subset, encompassing almost all cases of tumors with BRAF mutation (odds ratio = 203). Sporadic cases of mismatch repair deficiency occur almost exclusively as a consequence of CIMP-associated methylation of MLH1 . We propose a robust new marker panel to classify CIMP+ tumors.
TL;DR: It is demonstrated that in multiple FTD families with significant evidence for linkage to the same region on chromosome 17q21, FTD is caused by mutations in progranulin (PGRN) that are likely to create null alleles and identified mutations in PGRN as a cause of neurodegenerative disease.
Abstract: Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. A large proportion of FTD patients (35-50%) have a family history of dementia, consistent with a strong genetic component to the disease. In 1998, mutations in the gene encoding the microtubule-associated protein tau (MAPT) were shown to cause familial FTD with parkinsonism linked to chromosome 17q21 (FTDP-17). The neuropathology of patients with defined MAPT mutations is characterized by cytoplasmic neurofibrillary inclusions composed of hyperphosphorylated tau. However, in multiple FTD families with significant evidence for linkage to the same region on chromosome 17q21 (D17S1787-D17S806), mutations in MAPT have not been found and the patients consistently lack tau-immunoreactive inclusion pathology. In contrast, these patients have ubiquitin (ub)-immunoreactive neuronal cytoplasmic inclusions and characteristic lentiform ub-immunoreactive neuronal intranuclear inclusions. Here we demonstrate that in these families, FTD is caused by mutations in progranulin (PGRN) that are likely to create null alleles. PGRN is located 1.7 Mb centromeric of MAPT on chromosome 17q21.31 and encodes a 68.5-kDa secreted growth factor involved in the regulation of multiple processes including development, wound repair and inflammation. PGRN has also been strongly linked to tumorigenesis. Moreover, PGRN expression is increased in activated microglia in many neurodegenerative diseases including Creutzfeldt-Jakob disease, motor neuron disease and Alzheimer's disease. Our results identify mutations in PGRN as a cause of neurodegenerative disease and indicate the importance of PGRN function for neuronal survival.
TL;DR: Adalimumab was superior to placebo for induction of remission in patients with moderate to severe Crohn's disease naive to anti-TNF therapy and was well tolerated.
Icahn School of Medicine at Mount Sinai1, Mayo Clinic2, Johns Hopkins University3, Centers for Disease Control and Prevention4, Fremantle Hospital5, Harvard University6, Case Western Reserve University7, Stanford University8, University of Texas at Dallas9, American Academy of Pediatrics10, American Society of Anesthesiologists11, The American College of Financial Services12, National Institutes of Health13, University of Padua14, American College of Emergency Physicians15
TL;DR: There is no universal agreement on the definition of anaphylaxis or the criteria for diagnosis, so representatives from 16 different organizations or government bodies, including representatives from North America, Europe, and Australia, to continue working toward a universally accepted definition.
Abstract: There is no universal agreement on the definition of anaphylaxis or the criteria for diagnosis. In July 2005, the National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network convened a second meeting on anaphylaxis, which included representatives from 16 different organizations or government bodies, including representatives from North America, Europe, and Australia, to continue working toward a universally accepted definition of anaphylaxis, establish clinical criteria that would accurately identify cases of anaphylaxis with high precision, further review the evidence on the most appropriate management of anaphylaxis, and outline the research needs in this area.
TL;DR: The better outcomes for cardiovascular and total mortality seen in the overweight and mildly obese groups could not be explaining by adjustment for confounding factors and could be explained by the lack of discriminatory power of BMI to differentiate between body fat and lean mass.
University of Western Ontario1, Cornell University2, Mayo Clinic3, Erasmus University Rotterdam4, University of Illinois at Chicago5, University of Toronto6, Washington University in St. Louis7, University of California, Davis8, National Institutes of Health9, Newcastle upon Tyne Hospitals NHS Foundation Trust10, University of California, Los Angeles11, University of New Mexico12, Ludwig Maximilian University of Munich13
TL;DR: Using the same standards will help identify individuals in the early stages of cognitive impairment, will make studies comparable, and by integrating knowledge, will accelerate the pace of progress.
Abstract: Background and Purpose—One in 3 individuals will experience a stroke, dementia or both. Moreover, twice as many individuals will have cognitive impairment short of dementia as either stroke or dementia. The commonly used stroke scales do not measure cognition, while dementia criteria focus on the late stages of cognitive impairment, and are heavily biased toward the diagnosis of Alzheimer disease. No commonly agreed standards exist for identifying and describing individuals with cognitive impairment, particularly in the early stages, and especially with cognitive impairment related to vascular factors, or vascular cognitive impairment. Methods—The National Institute for Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) convened researchers in clinical diagnosis, epidemiology, neuropsychology, brain imaging, neuropathology, experimental models, biomarkers, genetics, and clinical trials to recommend minimum, common, clinical and research standards for the description and study of vascular cognitive impairment. Results—The results of these discussions are reported herein. Conclusions—The development of common standards represents a first step in a process of use, validation and refinement. Using the same standards will help identify individuals in the early stages of cognitive impairment, will make studies comparable, and by integrating knowledge, will accelerate the pace of progress. (Stroke. 2006;37:2220-2241.)
TL;DR: Increased attention to the systematic collection of validity evidence for scores from psychometric instruments will improve assessments in research, patient care, and education.
TL;DR: First clinical experience shows a considerably increased robustness for the imaging of patients with high heart rates, and the automatic separation of bones and iodine-filled vessels is demonstrated as a potential application of the dual-energy acquisition mode.
Abstract: We present a performance evaluation of a recently introduced dual-source computed tomography (DSCT) system equipped with two X-ray tubes and two corresponding detectors, mounted onto the rotating gantry with an angular offset of 90°. We introduce the system concept and derive its consequences and potential benefits for echocardiograph (ECG)-controlled cardiac CT and for general radiology applications. We evaluate both temporal and spatial resolution by means of phantom scans. We present first patient scans to illustrate the performance of DSCT for ECG-gated cardiac imaging, and we demonstrate first results using a dual-energy acquisition mode. Using ECG-gated single-segment reconstruction, the DSCT system provides 83 ms temporal resolution independent of the patient’s heart rate for coronary CT angiography (CTA) and evaluation of basic functional parameters. With dual-segment reconstruction, the mean temporal resolution is 60 ms (minimum temporal resolution 42 ms) for advanced functional evaluation. The z-flying focal spot technique implemented in the evaluated DSCT system allows 0.4 mm cylinders to be resolved at all heart rates. First clinical experience shows a considerably increased robustness for the imaging of patients with high heart rates. As a potential application of the dual-energy acquisition mode, the automatic separation of bones and iodine-filled vessels is demonstrated.
TL;DR: Real-time PCR assays provide sensitivity and specificity equivalent to that of conventional PCR combined with Southern blot analysis, and since amplification and detection steps are performed in the same closed vessel, the risk of releasing amplified nucleic acids into the environment is negligible.
Abstract: Real-time PCR has revolutionized the way clinical microbiology laboratories diagnose many human microbial infections. This testing method combines PCR chemistry with fluorescent probe detection of amplified product in the same reaction vessel. In general, both PCR and amplified product detection are completed in an hour or less, which is considerably faster than conventional PCR detection methods. Real-time PCR assays provide sensitivity and specificity equivalent to that of conventional PCR combined with Southern blot analysis, and since amplification and detection steps are performed in the same closed vessel, the risk of releasing amplified nucleic acids into the environment is negligible. The combination of excellent sensitivity and specificity, low contamination risk, and speed has made real-time PCR technology an appealing alternative to culture- or immunoassay-based testing methods for diagnosing many infectious diseases. This review focuses on the application of real-time PCR in the clinical microbiology laboratory.
TL;DR: Rituximab administered as induction or maintenance with CHOP chemotherapy significantly prolonged FFS in older DLBCL patients, which are consistent with an additive effect of ritUXimab.
Abstract: Purpose To address early and late treatment failures in older patients with diffuse large B-cell lymphoma (DLBCL), we designed a two-stage randomized trial of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) versus rituximab plus CHOP (R-CHOP), with a second random assignment to maintenance rituximab (MR) or observation in responding patients. Patients and Methods Untreated DLBCL patients who were 60 years or older were randomly assigned to R-CHOP (n = 318) or CHOP (n = 314); 415 responders were randomly assigned to MR (n = 207) or observation (n = 208). The primary end point was failure-free survival (FFS). All P values were two sided. Results Three-year FFS rate was 53% for R-CHOP patients and 46% for CHOP patients (P = .04) at a median follow-up time of 3.5 years. Two-year FFS rate from second random assignment was 76% for MR compared with 61% for observation (P = .009). No significant differences in survival were seen according to induction or maintenance therapy. FFS was prolonged wi...
TL;DR: In this article, the authors assess the frequency of self-perceived medical errors among resident physicians and determine the association of perceived medical errors with resident quality of life, burnout, depression, and empathy using validated metrics.
Abstract: ContextMedical errors are associated with feelings of distress in physicians, but little is known about the magnitude and direction of these associations.ObjectiveTo assess the frequency of self-perceived medical errors among resident physicians and to determine the association of self-perceived medical errors with resident quality of life, burnout, depression, and empathy using validated metrics.Design, Setting, and ParticipantsProspective longitudinal cohort study of categorical and preliminary internal medicine residents at Mayo Clinic Rochester. Data were provided by 184 (84%) of 219 eligible residents. Participants began training in the 2003-2004, 2004-2005, and 2005-2006 academic years and completed surveys quarterly through May 2006. Surveys included self-assessment of medical errors and linear analog scale assessment of quality of life every 3 months, and the Maslach Burnout Inventory (depersonalization, emotional exhaustion, and personal accomplishment), Interpersonal Reactivity Index, and a validated depression screening tool every 6 months.Main Outcome MeasuresFrequency of self-perceived medical errors was recorded. Associations of an error with quality of life, burnout, empathy, and symptoms of depression were determined using generalized estimating equations for repeated measures.ResultsThirty-four percent of participants reported making at least 1 major medical error during the study period. Making a medical error in the previous 3 months was reported by a mean of 14.7% of participants at each quarter. Self-perceived medical errors were associated with a subsequent decrease in quality of life (P = .02) and worsened measures in all domains of burnout (P = .002 for each). Self-perceived errors were associated with an odds ratio of screening positive for depression at the subsequent time point of 3.29 (95% confidence interval, 1.90-5.64). In addition, increased burnout in all domains and reduced empathy were associated with increased odds of self-perceived error in the following 3 months (P=.001, P<.001, and P=.02 for depersonalization, emotional exhaustion, and lower personal accomplishment, respectively; P=.02 and P=.01 for emotive and cognitive empathy, respectively).ConclusionsSelf-perceived medical errors are common among internal medicine residents and are associated with substantial subsequent personal distress. Personal distress and decreased empathy are also associated with increased odds of future self-perceived errors, suggesting that perceived errors and distress may be related in a reciprocal cycle.
TL;DR: Lenalidomide can reduce transfusion requirements and reverse cytologic and cytogenetic abnormalities in patients who have the myelodysplastic syndrome with the 5q31 deletion.
Abstract: Background Severe, often refractory anemia is characteristic of the myelodysplastic syndrome associated with chromosome 5q31 deletion. We investigated whether lenalidomide (CC5013) could reduce the transfusion requirement and suppress the abnormal 5q31− clone in patients with this disorder. Methods One hundred forty-eight patients received 10 mg of lenalidomide for 21 days every 4 weeks or daily. Hematologic, bone marrow, and cytogenetic changes were assessed after 24 weeks of treatment by an intention-to-treat analysis. Results Among the 148 patients, 112 had a reduced need for transfusions (76%; 95% confidence interval [CI], 68 to 82) and 99 patients (67%; 95% CI, 59 to 74) no longer required transfusions, regardless of the karyotype complexity. The response to lenalidomide was rapid (median time to response, 4.6 weeks; range, 1 to 49) and sustained; the median duration of transfusion independence had not been reached after a median of 104 weeks of follow-up. The maximum hemoglobin concentration reached...
TL;DR: Pupillary light response, corneal reflexes, motor responses to pain, myoclonus status epilepticus, serum neuron-specific enolase, and somatosensory evoked potential studies can reliably assist in accurately predicting poor outcome in comatose patients after cardiopulmonary resuscitation for cardiac arrest.
Abstract: Objective: To systematically review outcomes in comatose survivors after cardiac arrest and cardiopulmonary resuscitation (CPR). Methods: The authors analyzed studies (1966 to 2006) that explored predictors of death or unconsciousness after 1 month or unconsciousness or severe disability after 6 months. Results: The authors identified four class I studies, three class II studies, and five class III studies on clinical findings and circumstances. The indicators of poor outcome after CPR are absent pupillary light response or corneal reflexes, and extensor or no motor response to pain after 3 days of observation (level A), and myoclonus status epilepticus (level B). Prognosis cannot be based on circumstances of CPR (level B) or elevated body temperature (level C). The authors identified one class I, one class II, and nine class III studies on electrophysiology. Bilateral absent cortical responses on somatosensory evoked potential studies recorded 3 days after CPR predicted poor outcome (level B). Burst suppression or generalized epileptiform discharges on EEG predicted poor outcomes but with insufficient prognostic accuracy (level C). The authors identified one class I, 11 class III, and three class IV studies on biochemical markers. Serum neuron-specific enolase higher than 33 μg/L predicted poor outcome (level B). Ten class IV studies on brain monitoring and neuroimaging did not provide data to support or refute usefulness in prognostication (level U). Conclusion: Pupillary light response, corneal reflexes, motor responses to pain, myoclonus status epilepticus, serum neuron-specific enolase, and somatosensory evoked potential studies can reliably assist in accurately predicting poor outcome in comatose patients after cardiopulmonary resuscitation for cardiac arrest.
TL;DR: Among residents of Olmsted County, Minnesota, MGUS was found in 3.2% of persons 50 years of age or older and 5.3 percent of persons 70 years ofAge or older, which are higher in men than in women.
Abstract: BACKGROUND The prevalence of monoclonal gammopathy of undetermined significance (MGUS), a premalignant plasma-cell disorder, among persons 50 years of age or older has not been accurately determined. We used sensitive laboratory techniques to ascertain the prevalence of MGUS in a large population in a well-defined geographic area. METHODS We identified all living residents of Olmsted County, Minnesota, as of January 1, 1995. We obtained serum that remained after the performance of routine clinical tests at Mayo Clinic or asked subjects for whom such serum was unavailable to provide a sample. Agarose-gel electrophoresis was performed on all serum samples, and any serum sample with a discrete band of monoclonal protein or thought to have a localized band was subjected to immunofixation. RESULTS Serum samples were obtained from 21,463 of the 28,038 enumerated residents 50 years of age or older (76.6 percent). MGUS was identified in 694 (3.2 percent) of these persons. Age-adjusted rates were higher in men than in women (4.0 percent vs. 2.7 percent, P<0.001). The prevalence of MGUS was 5.3 percent among persons 70 years of age or older and 7.5 percent among those 85 years of age or older. The concentration of monoclonal immunoglobulin was less than 1.0 g per deciliter in 63.5 percent and at least 2.0 g per deciliter in only 4.5 percent of 694 persons. The concentration of uninvolved immunoglobulins was reduced in 27.7 percent of 447 persons tested, and 21.5 percent of 79 tested had a monoclonal urinary light chain. CONCLUSIONS Among residents of Olmsted County, Minnesota, MGUS was found in 3.2 percent of persons 50 years of age or older and 5.3 percent of persons 70 years of age or older.
TL;DR: The results of this trial demonstrate the efficacy and manageable adverse-event profile of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC.
Abstract: ContextCurrent treatment options for metastatic renal cell carcinoma (RCC) are limited and there is a need to identify novel and effective therapies. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, which has shown activity in an initial study of cytokine-refractory metastatic RCC patients.ObjectiveTo confirm the antitumor efficacy of sunitinib as second-line treatment in patients with metastatic clear-cell RCC, the predominant cell type of this malignancy.Design, Setting, and PatientsOpen-label, single-arm, multicenter clinical trial. Patients were enrolled between February and November 2004, with follow-up continuing until disease progression, unacceptable toxicity, or withdrawal of consent. The reported data apply through August 2005. Patients (N = 106) had metastatic clear-cell RCC, which had progressed despite previous cytokine therapy.InterventionRepeated 6-week cycles of sunitinib, 50 mg per day given orally for 4 consecutive weeks followed by 2 weeks off per treatment cycle.Main Outcome MeasuresAssessment of clinical response, degree of tumor regression on imaging studies using the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Primary end point was overall objective response rate (complete plus partial). Secondary end points were progression-free survival and safety. Response was evaluated by independent third-party core imaging laboratory and by treating physicians (investigator assessment).ResultsAll 106 patients received sunitinib and were included in the intent-to-treat population for safety analyses. Of these, 105 patients were evaluable for efficacy analyses. The objective response rate according to an independent third-party assessment resulted in 36 patients with partial response (34%; 95% confidence interval, 25%-44%), and a median progression-free survival of 8.3 months (95% confidence interval, 7.8-14.5 months). The most common adverse events experienced by patients were fatigue in 30 (28%) and diarrhea 21 (20%). Neutropenia, elevation of lipase, and anemia were the most common laboratory abnormalities observed in 45 (42%), 30 (28%), and 27 (26%) patients, respectively.ConclusionThe results of this trial demonstrate the efficacy and manageable adverse-event profile of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC.Trial Registrationclinicaltrials.gov Identifier: NCT00077974
TL;DR: The Task Force recommends testosterone therapy for symptomatic men with androgen deficiency, who have low testosterone levels, to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density.
Abstract: Objective: The objective was to provide guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men Participants: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, five additional experts, a methodologist, and a professional writer The Task Force received no corporate funding or remuneration Evidence: The Task Force used systematic reviews of available evidence to inform its key recommendations The Task Force used consistent language and graphical descriptions of both the strength of recommendation and the quality of evidence, using the recommendations of the Grading of Recommendations, Assessment, Development, and Evaluation group Consensus Process: Consensus was guided by systematic reviews of evidence and discussions during three group meetings, several conference calls, and e-mail communications The drafts prepared by the panelists with the help of a professional writer were reviewed successively by Th
Washington University in St. Louis1, Leiden University2, Westmead Hospital3, Boston Children's Hospital4, Royal Free Hospital5, Queen's University6, University of Milan7, French Institute of Health and Medical Research8, Mayo Clinic9, National Archives and Records Administration10, Royal Hallamshire Hospital11, University of Hamburg12, Scripps Research Institute13, Christian Medical College & Hospital14
TL;DR: Six categories of von Willebrand disease correlate with important clinical features and therapeutic requirements, and certain VWD types, especially type 1 and type 2A, encompass several pathophysiologic mechanisms that sometimes can be distinguished by appropriate laboratory studies.
TL;DR: The normal size and phasic function of the left atrium is discussed, the clinically important aspects and pitfalls of evaluating LA size, and the methods for assessing LA function using echocardiography are outlined.
TL;DR: In this paper, a gain-of-function MPL mutation, MPLW515L, was described in patients with JAK2V617F-negative myelofibrosis with myeloid metaplasia (MMM).
TL;DR: This study reveals an evolutionarily conserved molecular mechanism of targeting DNA repair proteins to DSBs by direct recognition of H4-K20me2 through direct binding of 53BP1 and Crb2 to histone H4.