Prognostic Indicator Of Outcome Research Articles

Proteomics and ovarian cancer: Integrating proteomics information into clinical care

The power of proteomics allows unparalleled opportunity to query the molecular mechanisms of a malignant cell and the tumor microenvironment in patients with ovarian cancer and other solid tumors. This information has given us insight into the perturbations of signaling pathways within tumor cells and has aided the discovery of new drug targets for the tumor and possible prognostic indicators of outcome and disease response to therapy. Proteomics analysis of serum and ascites has also given us sources with which to discover possible early markers for the presence of new disease and for the progression of established cancer throughout the course of treatment. Unfortunately, this wealth of information has yielded little to date in changing the clinical care of these patients from a diagnostic, prognostic, or treatment perspective. The rational examination and translation of proteomics data in the context of past clinical trials and the design of future clinical trials must occur before we can march forward into the future of personalized medicine.

A prospective study of the effect of nursing home residency on mortality following hip fracture

The strength of nursing home residence as a prognostic indicator of outcome following hip fracture has not previously been examined in Australia. The aim of the study was to examine the influence of nursing home residency on mortality after sustaining an acute hip fracture. A prospective study of all adults aged 65 years and over presenting to a single tertiary referral hospital for management of a proximal femoral fracture between July 2003 and September 2006. Residential status was obtained at admission. Patients were followed up to September 2007 (minimum 12 months). Relative risk values for mortality were calculated comparing nursing home residents with non-nursing home residents. Survival analysis was performed. Relative risk of death was higher in nursing home patients compared with non-nursing home patients. The difference was greater in the immediate period (30 days) post-injury (relative risk 1.9, 95% confidence interval 1.0-3.6, P= 0.04) than after 12 months (relative risk 1.5, 95% confidence interval 1.2-1.8, P= 0.001). Survival analysis showed that 25% of patients in the nursing home group died by 96 days post-injury, compared with 435 days in the non-nursing home group. Nursing home residence confers an increased risk of death following hip fracture; this difference is greater in the immediate post-injury period. The relative risk of death decreases over time to equal previously reported comparative mortality rates between nursing home residents and community dwellers without hip fracture.

PROGNOSTIC POWER OF THROMBOCYTOPENIA IN CRITICALLY ILL PATIENTS

PURPOSE: Thrombocytopenia is common in ICU patients and some studies suggested a prognostic role in combination with other factors. Our study is designed to evaluate if platelet count could be used as a prognostic indicator of outcome in critically ill patients.

Are there any prognostic indicators of outcomes in cases of head and neck necrotising soft tissue infections?

Are there any prognostic indicators of outcomes in cases of head and neck necrotising soft tissue infections?

Does having surplus embryos to freeze serve as a prognostic indicator of ivf outcome?

OBJECTIVE: To evaluate whether having supernumerary embryos available for cryopreservation may be a marker for discriminating patients who produce embryos with greater implantation potential and thus have a better prognosis in their fresh IVF cycle. DESIGN: Retrospective analysis. MATERIALS AND METHODS: Patients <35 yrs with normal FSH (<10IU/L) who underwent a fresh ET from 12/02-03/09 were included. Cycles were classified by ET day (D3/D5), and subclassified based on blastocyst availability for cryopreservation. Independent of ET day, surplus embryos are assessed and cryopreserved on D5/D6 if morphologically optimal. Analysis of outcome including implantation (IR), clinical pregnancy (CPR) and loss rates was performed for each group. RESULTS: 2071 ETs were identified, of which 990 were performed on D3 and 1081 on D5. Although the mean embryos transferred was similar between the cryo and no cryo groups for each type of transfer, significantly higher CPR and IR were noted for the subgroups having surplus embryos frozen.Tabled 1Day 3 ET n=990Day 5 ET n=1081CRYO n=216NO CRYO n=774CRYO n=674NO CRYO n=407Age31.2±2.831.4±2.931.1±2.931.2±3.0FSH (IU/L)6.4±2.06.8±1.86.3±1.96.5±1.6Number of ET2.6±0.62.5±0.82.2±0.42.4±0.7CPR149/216 (69%)∗450/774 (58.1%)∗486/674(72.1%)˜225/407(55.3%)˜IR247/561(44%)∧702/1971(35.6%)∧758/1447(52.4%)⋄334/987(33.8%)⋄Loss Rate23/149 (15.4%)49/450 (10.9%)54/486 (11.1%)21/225 (9.3%)∗ p=0.0051, ∼ p=0.0336, ∧ p <0.0001, ⋄ p<0.0001. Open table in a new tab ∗ p=0.0051, ∼ p=0.0336, ∧ p <0.0001, ⋄ p<0.0001. CONCLUSIONS: Patients who have surplus high quality embryos frozen demonstrate higher CPRs in the fresh cycle from which these originated. We hypothesize that embryo cohort-specific variables exist, and that the reproductive competence of sibling embryos may predict developmental competence as measured by IVF cycle outcomes. Surplus blastocysts available for cryopreservation may be used as a prognostic indicator of outcome in young patients who have undergone an ET in the same cycle.

Resuscitation with Hypertonic Saline–Dextran Reduces Serum Biomarker Levels and Correlates with Outcome in Severe Traumatic Brain Injury Patients

In the treatment of severe traumatic brain injury (TBI), the choice of fluid and osmotherapy is important. There are practical and theoretical advantages to the use of hypertonic saline. S100B, neuron-specific enolase (NSE), and myelin-basic protein (MBP) are commonly assessed biomarkers of brain injury with potential utility as diagnostic and prognostic indicators of outcome after TBI, but they have not previously been studied in the context of fluid resuscitation. This randomized controlled trial compared serum concentrations of S100B, NSE, and MBP in adult severe TBI patients resuscitated with 250 mL of 7.5% hypertonic saline plus 6% dextran70 (HSD; n = 31) versus 0.9% normal saline (NS; n = 33), and examined their relationship with neurological outcome at discharge. Blood samples drawn on admission (<or=3 h post-injury), and at 12, 24, and 48 h post-resuscitation were assayed by ELISA for the selected biomarkers. Serial comparisons of biomarker concentrations were made by ANOVA, and relationships between biomarkers and outcome were assessed by multiple regression. On admission, mean (+/-SEM) S100B and NSE concentrations were increased 60-fold (0.73 +/- 0.08 microg/L) and sevenfold (37.0 +/- 4.8 microg/L), respectively, in patients resuscitated with NS, compared to controls (0.01 +/- 0.01 and 6.2 +/- 0.6, respectively). Compared with NS resuscitation, S100B and NSE were twofold and threefold lower in HSD-treated patients and normalized within 12 h. MBP levels were not significantly different from controls in either treatment arm until 48 h post-resuscitation, when a delayed increase (0.58 +/- 0.29 microg/L) was observed in NS-treated patients. Biomarkers were elevated in the patient group showing an unfavorable outcome. HSD-resuscitated patients with favorable outcomes exhibited the lowest serum S100B and NSE concentrations, while maximal levels were found in NS-treated patients with unfavorable outcomes. The lowest biomarker levels were seen in survivors resuscitated with HSD, while maximal levels were in NS-resuscitated patients with fatal outcome. Pre-hospital resuscitation with HSD is associated with a reduction in serum S100B, NSE, and MBP concentrations, which are correlated with better outcome after severe TBI.

Myoglobin as a prognostic indicator for outcome in dogs with gastric dilatation‐volvulus

To determine whether myoglobin (Mb) is a useful prognostic indicator for outcome and to investigate any relationship between Mb and mortality in dogs with gastric dilatation-volvulus (GDV). Prospective study. Veterinary teaching hospital. Seventy-two dogs with GDV. Blood sampling. Mb levels were measured at the time of diagnosis (Mbt0), 24 hours (Mbt1), and 48 hours (Mbt2) after signs of GDV were recognized. Fifty-seven dogs survived (group I) and 15 dogs did not survive (group II). Mbt0 differed significantly between groups (P=0.04). Mbt0 in group I ranged from <30 to >700 ng/mL (n=57, median 74 ng/mL), and in group II from 34 to >700 ng/mL (n=15, median 238 ng/mL). Analysis of a receiver operating characteristic curve of Mbt0 suggested that the best single cutpoint would be 168 ng/mL (sensitivity 60.0%, specificity 84.2%). Fifty percent of dogs with Mbt0>168 ng/mL were euthanized, while 88.9% with Mbt0<168 ng/mL survived. Mbt1 and Mbt2 differed significantly between groups I and II. Mbt1 in group I ranged from 32 to >700 ng/mL (n=55, median 123 ng/mL), and Mbt1 in group II ranged from 131 to 643 ng/mL (n=7, median 343 ng/mL) (P=0.006). Mbt2 in group I ranged from 30 to 597 ng/mL (n=54, median 101 ng/mL), and in group II from 141 to >700 ng/mL (n=8, median 203 ng/mL) (P=0.02). In this study, Mbt0 is a moderately sensitive and specific prognostic indicator. Almost 90% of the dogs below the cutpoint survived to discharge, whereas 50% with Mbt0 above the cutpoint did not survive.

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Response to chemotherapy predicts survival following resection of hepatic colo‐rectal metastases in patients treated with neoadjuvant therapy

Prognosis of patients following resection of CRC metastases to the liver has traditionally been predicted by clinical risk factors. In the era of neoadjuvant chemotherapy, determination of new prognostic indicators of outcome are necessary. This retrospective study includes patients with CRC liver metastases, who received oxaliplatin or irinotecan based neoadjuvant chemotherapy and underwent R0 resection. Patients were followed by CT and PET-CT, before, during and after chemotherapy and surgery. The predictive value of the Memorial Sloan-Kettering Cancer Center Clinical Score (MSKCC-CS) and degree of response to chemotherapy (measured by CT and PET-CT), were analyzed by univariate and multivariate COX regression. Included are 54 patients. Overall 1-, 2-, 3-year survival rates 88%, 70%, and 39%. Response to chemotherapy on CT was a significant predictor of survival on univariate (P = 0.03) and multivariate analysis (P = 0.03), whereas MSKCC-CS and response to chemotherapy on PET-CT were not. Multivariate analysis demonstrated response to chemotherapy as a predictor of time to recurrence on CT (P = 0.02) and PET-CT (P = 0.03), while the MSKCC-CS (P = 0.64) was not. In this cohort of patients treated by neoadjuvant chemotherapy, the outcome was not predicted by the traditional clinical scoring system, but rather by response to chemotherapy as evaluated by CT and PET-CT.

Pathological tumour diameter predicts risk of conventional subtype in small renal cortical tumours

To examine whether pathological tumour diameter assists in predicting conventional vs other histological subtypes in renal cortical tumours (RCTs) of <or=4 cm diameter. In all, 393 patients from Columbia University's Comprehensive Urologic Oncology Database who underwent radical or partial nephrectomy between 1988 and 2005 and had RCTs of <or=4 cm were analysed. Logistic regression analysis using tumour diameter as a continuous variable was used to determine whether size predicted histological subtype. Odds ratios (ORs) were calculated to estimate the likelihood of having conventional histology based on diameter. The median patient age at surgery was 64.3 years and median tumour diameter was 3 cm, In all, 256 (65.1%) of the RCTs were conventional subtype and 137 (34.9%) were nonconventional. Logistic regression analysis showed that for every 1 cm increase in diameter up to 4 cm, the RCT was 1.27 times more likely to be conventional (P = 0.020). The ORs showed that a 4-cm RCT was 2.06 times more likely to be conventional than tumours of 0.6-1.5 cm. There was a positive association between RCT diameter and the risk of having conventional renal cell carcinoma (RCC). Given that RCC histological subtype is a prognostic indicator for outcome, these findings may be applied in the selection of treatment options. Further studies investigating tumour size and other variables predictive of tumour histology will help clinicians better predict the RCC subtype.

Serum YKL-40 levels as a prognostic factor in patients with locally advanced breast cancer

YKL-40 is a growth factor for connective tissue cells; it also stimulates the migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum levels have been associated with poorer prognosis in metastatic breast cancer. In the present study we evaluated the prognostic role of serum YKL-40 levels in patients with locally advanced breast cancer. YKL-40 levels were measured using ELISA in serum samples obtained from 45 breast cancer patients prior to surgery and chemotherapy. The median follow-up time was 46 months (range, 10-96 months). All patients underwent surgery after chemotherapy. During the follow-up period, 21 patients relapsed and there were 17 deaths. The median serum YKL-40 concentration in patients with locally advanced breast cancer was 149.5 mug/l (range, 25.0-1021.3 microg/l). This was higher than levels observed in healthy female controls but the difference was not significant (P=0.44). Serum YKL-40 levels were also higher in patients with tumour size >2 cm and node-positive disease but again the differences were not significant (P>0.05). Tumour volume was correlated with serum YKL-40 levels (r=0.308, P=0.039). High serum YKL-40 levels were associated with shorter disease-free and overall survival although this trend failed to reach significance (P>0.05). Multivariate analysis including tumour size, lymph node status, oestrogen and progesterone receptor status, tumour grade, and serum YKL-40 levels indicated that serum YKL-40 levels were an independent prognostic variable for overall survival (hazard ratio, 1.004; 95% confidence intervals: 1.00, 1.07; P=0.027). Tumour size, lymph node status and oestrogen receptor status were also independent prognostic variables for overall survival (P<0.05). Our results show that serum levels of the growth factor YKL-40 may be a useful prognostic indicator of outcome for patients with locally advanced breast cancer. Further studies are required to fully elucidate the biological function of YKL-40 in breast cancer.

Prognostic Indicators of Outcome in Superior Vena Cava Obstruction in Lung Cancer

Prognostic Indicators of Outcome in Superior Vena Cava Obstruction in Lung Cancer

69. Surgical Treatment of Sacral Chordomas with Pre-operative Arterial Embolization and Prognostic Indicators of Outcome

69. Surgical Treatment of Sacral Chordomas with Pre-operative Arterial Embolization and Prognostic Indicators of Outcome

Functional Magnetic Resonance Imaging of Hearing-Impaired Children Under Sedation Before Cochlear Implantation

To investigate functional magnetic resonance imaging (fMRI) in pediatric cochlear implantation candidates with residual hearing who are under sedation for evaluation of auditory function. During fMRI, subjects heard a random sequence of tones (250-4000 Hz) presented 10 dB above hearing thresholds. Tones were interleaved with silence in a block-periodic fMRI design with 30-second on-off intervals. Twenty-four axial sections (5 mm thick) covering most of the brain were obtained every 3 seconds for a total acquisition time of 5.5 minutes. Single tertiary academic medical institution. Severely to profoundly hearing-impaired children (n=10; mean age, 49.1 months). During fMRI, subjects were awake (n=2) or sedated with pentobarbital sodium if their weight was 10 kg or greater (n=4) or chloral hydrate if their weight was less than 10 kg (n=4). Detection of brain activation by fMRI in the primary auditory cortex (A1) in hearing-impaired patients under sedation, and correlation of A1 activation with hearing levels measured after cochlear implantation. In most subjects, fMRI detected significant levels of activation in the A1 region before cochlear implantation. The improvement in hearing threshold after cochlear implantation correlated strongly (linear regression coefficient, R=0.88) with the amount of activation in the A1 region detected by fMRI before cochlear implantation. Functional MRI can be considered a means of assessing residual function in the A1 region in sedated hearing-impaired toddlers. With improvements in acquisition, processing, and sedation methods, fMRI may be translated into a prognostic indicator for outcome after cochlear implantation in infants.

Lymphatic vessel density in the neoplastic progression of Barrett’s oesophagus to adenocarcinoma

Background: Oesophageal adenocarcinoma is an aggressive neoplasm with poor prognosis as a result of early lymph node metastasis. Aims: To measure lymphatic vessel density (LVD) in the neoplastic progression from...

Interleukin 6 is a prognostic indicator of outcome in severe intra-abdominal sepsis.

Levels of plasma cytokines and circulating endotoxin were assessed in 41 patients with severe intra-abdominal sepsis. Comparison was made with the Acute Physiology And Chronic Health Evaluation (APACHE) II scoring system. Blood samples were taken within 24 h of onset of the sepsis syndrome and at serial times thereafter. Increased levels of interleukin (IL) 6 (range 50-25,500 pg/ml) were detectable in all patients with sepsis. Eighteen of the 19 deaths were attributable to sepsis and higher levels of IL-6 at the onset of the sepsis syndrome correlated with a poor outcome. The sensitivity of IL-6 concentration in predicting mortality was 86.4 per cent with a specificity of 78.9 per cent and an overall correct classification rate of 82.9 per cent. IL-6 level was a better predictor than APACHE II score (sensitivity 72.7 per cent, specificity 57.9 per cent, correct classification rate 65.9 per cent). Levels of tumour necrosis factor alpha, IL-1 beta and endotoxin did not correlate with mortality rate. Plasma IL-6 concentrations may help in planning future strategies to decrease the mortality rate associated with sepsis.

Adrenomedullin in Heart Failure: Potential Therapeutic Implications

Adrenomedullin (AM) may play a role in the pathophysiology of heart failure. Plasma levels of AM are raised in cardiovascular disease in proportion to severity of cardiac dysfunction, and plasma AM levels measured in acute myocardial infarction and heart failure are a useful prognostic indicator of outcome. AM administration in both experimental and human heart failure induces a beneficial spectrum of biological action including reduced arterial and atrial pressures, improved cardiac output, inhibition of plasma aldosterone and preservation or augmentation of urinary sodium excretion. Combining AM administration with either angiotensin-converting enzyme inhibition or neutral endopeptidase inhibition results in augmentation of the hemodynamic and renal effects of the individual treatments. Manipulating the AM system may prove beneficial as an adjunctive therapeutic strategy in cardiac disease.

Residual complaints following lumbar disc surgery: prognostic indicators of outcome

Physical as well as psychological features might be important prognostic factors for residual complaints following lumbar disc surgery in primary care. No studies have yet investigated both factors simultaneously. The aim of this prospective cohort study was to identify indicators of the short and long-term outcome of residual complaints following lumbar disc surgery. Patients ( n=105), aged between 18 and 65 years, were included if they still suffered residual complaints 6 weeks after first-time lumbar disc surgery and had therefore been referred to physiotherapy. All potential indicators were measured at baseline except treatment expectancy, which was measured after two treatment sessions enabling patients to rate treatment expectancy based on their actual perception of the treatment. Dimensions of recovery included perceived recovery, functional status, and pain intensity (back and leg) at the 3-month and 12-month follow-up. It was found that high treatment expectancy was associated with a favorable outcome on perceived recovery and functional status, both at the 3 and the 12-month follow-up. Taking pain medication and a poor functional status at baseline were associated with poor perceived recovery and functional status at both follow-up measurements. Leg pain and back pain at baseline were associated with residual leg and back pain at the 3 and the 12-month follow-up, respectively. The results for perceived recovery and functional status were rather robust. However, for leg pain and back pain, the results were less stable. Apparently, the clinical course to recovery of residual leg pain and residual back pain is not strongly influenced by these indicators.

Conservative treatment for shoulder pain: Prognostic indicators of outcome

Ginn KA, Cohen ML. Conservative treatment for shoulder pain: prognostic indicators of outcome. Arch Phys Med Rehabil 2004;85:1231–5. Objectives To investigate the long-term clinical outcome and to identify factors that predict that outcome, after conservative treatment of patients who have shoulder pain with or without accompanying stiffness. Design Cohort study. Setting Outpatient clinic. Participants Eighty-two subjects who had participated in a randomized controlled trial that compared the short-term effectiveness of conservative treatment for chronic, unilateral shoulder pain of mechanical origin with and without accompanying stiffness, and who were available for longer term follow-up 6 months after the cessation of formal treatment. Interventions Conservative treatment consisting of various combinations of exercise therapy, passive joint mobilization, electrophysical modalities, and corticosteroid injections. Main outcome measures Pain intensity, functional limitation, perceived change in symptoms, active range of motion, muscle force, and clinical and demographic variables. Results Patients showed significant improvement in all outcome measurements in the long-term whether or not their shoulder pain was accompanied by stiffness. Long-term outcome was not predicted by hand dominance, clinical history of the shoulder condition, severity of the shoulder problem, or shoulder mechanics. Conclusions Patients with chronic shoulder pain, with or without accompanying stiffness, can expect significant decreases in shoulder pain and improvements in shoulder function in the long term after conservative treatment.

Phase II study of EPOCH infusional chemotherapy in relapsed or refractory Hodgkin's lymphoma (HL). A report on toxicity, efficacy and prognostic indicators of outcome

6598 Background: In relapsed/refractory HL, an effective and well tolerated salvage regimen has important roles both prior to autologous stem cell transplant (SCT) and as palliative therapy in patients (pts) who are ineligible for or have failed SCT. Methods: Eligible pts had relapsed/refractory HL and adequate organ function unless due to HL. Pts received fixed dose EPOCH chemotherapy (etoposide 200 mg/m2, vincristine 1.6 mg/m2 (no cap) and doxorubicin 40 mg/m2 CIVI x 96-hrs D1–4; cyclophosphamide 750 mg/m2 IV D5 and prednisone 60 mg/m2 qd D1–6 ) with G-CSF q21 days until disease progression or stabilization over ≥ 2 cycles. Results: Of 54 pts, median (range) age was 31 yrs (19–64), 35 (66%) were male, stage was III in 11(21%) and IV in 30(56%), and 29 (55%) had B symptoms. Histology included nodular sclerosis 34 (64%), mixed cellularity 3 (25%), and lymphocyte depleted 5 (9%) classical HL, and nodular lymphocyte predominant HL 1 (2%). 24 (45%) pts had had ≥ 2 prior regimens, 27 (51%) pts received chemotherapy within the previous 10 mos, and 40 (75%) pts had responded to their last treatment. Over 202 cycles, toxicities included fever and neutropenia on 9 (4%), grade (gr) 4 neutropenia on 31 (15%), gr 4 thrombocytopenia on 20 (10%), and ≥ gr 2 gastrointestinal toxicity on 20 (10%) cycles; ≥ gr 2 cardiotoxicity occurred in 2 (4%) and ≥ gr 2 neurotoxicity in 11 (20%) pts. There was one treatment related death. 45 (84%) pts responded with 23 (44%) CR and 21 (40%) PR. With a median follow-up of 68 mos, the median progression-free (PFS) and overall survivals (OS) are 10 and 40 mos, and at 68 mos median follow-up, PFS and OS are 21% and 41%. Among 33 pts who underwent SCT, median PFS is 15 mos and OS has not been reached. Multivariate analysis revealed that the no. of prior drugs and response to the preceding regimen significantly influenced OS and PFS; in addition PFS was significantly influenced by performance status and mos since previous chemotherapy. Conclusions: EPOCH is well tolerated and has a high response rate in relapsed/refractory HL. It should be considered as salvage therapy prior to SCT or for palliation in incurable HL. No significant financial relationships to disclose.