The oncoprotein-18/stathmin 1 (STMN1), involved in cell progression and migration, is associated with clinical outcome in breast cancer. Here we aim to investigate its clinical significance in ...urinary bladder cancer and its possibilities as a therapeutic target.
Immunohistochemical analyses of STMN1 protein expression were performed in three patient cohorts: cohort I (n=115 Ta, n=115 T1, n=112 T2-4 stages), cohort II, based on randomised controlled trials (n=239 T1-T4), and cohort III of primary tumour/matched metastasis (n=90 T1-T4). The effects of STMN1 on cell proliferation and migration were evaluated in the urinary bladder cancer cell line, T24, by inhibiting STMN1-cellular expression using siRNA.
In cohort I, high STMN1 expression correlated to shorter disease-specific survival hazard ratio (HR)=2.04 (95% confidence interval (CI) 1.13-3.68; P=0.02), elevated p53- (P<0.001) and Ki67-protein levels (P<0.001). The survival result was validated in cohort II: HR=1.76 (95% CI 1.04-2.99; P=0.03). In the metastatic bladder cancer material, 70% of the patients were STMN1-positive in both the primary tumour and matched metastases. In vitro, the growth and migration of the T24 cells were significantly reduced (P<0.01, P<0.0001, respectively), when transfecting the cells with STMN1-siRNA.
STMN1 protein expression has prognostic significance but is primarily a potential treatment target in urinary bladder cancer.
Context:
Optimal levels of vitamin D have been a topic of heavy debate, and the correlation between 25-hydroxyvitamin D 25(OH)D levels and mortality still remains to be established.
Objective:
The ...aim of the study was to determine the association between all-cause mortality and serum levels of 25(OH)D, calcium, and PTH.
Design and Setting:
We conducted a retrospective, observational cohort study, the CopD Study, in a single laboratory center in Copenhagen, Denmark.
Participants:
Serum 25(OH)D was analyzed from 247,574 subjects from the Copenhagen general practice sector. In addition, serum levels of calcium, albumin-adjusted calcium, PTH, and creatinine were measured in 111,536; 20,512; 34,996; and 189,496 of the subjects, respectively.
Main Outcome Measures:
Multivariate Cox regression analysis was used to compute hazard ratios for all-cause mortality.
Results:
During follow-up (median, 3.07 yr), 15,198 (6.1%) subjects died. A reverse J-shaped association between serum level of 25(OH)D and mortality was observed. A serum 25(OH)D level of 50–60 nmol/liter was associated with the lowest mortality risk. Compared to 50 nmol/liter, the hazard ratios (95% confidence intervals) of all-cause mortality at very low (10 nmol/liter) and high (140 nmol/liter) serum levels of 25(OH)D were 2.13 (2.02–2.24) and 1.42 (1.31–1.53), respectively. Similarly, both high and low levels of albumin-adjusted serum calcium and serum PTH were associated with an increased mortality, and secondary hyperparathyroidism was associated with higher mortality (P < 0.0001).
Conclusion:
In this study from the general practice sector, a reverse J-shaped relation between the serum level of 25(OH)D and all-cause mortality was observed, indicating not only a lower limit but also an upper limit. The lowest mortality risk was at 50–60 nmol/liter. The study did not allow inference of causality, and further studies are needed to elucidate a possible causal relationship between 25(OH)D levels, especially higher levels, and mortality.
Purpose
To evaluate the outcome of degenerative lumbar spine surgery in a credible way, patient-reported outcome measures (PROMs) should be assessed after an adequate follow-up period. Most ...authors/journals consider a follow-up period of less than two years to be too short. The purpose of this study was to explore the possibility of restricting follow-up to one year.
Methods
Adult patients operated between 1998 and 2017 were retrieved from Swespine (Lumbar Disc Herniation
n
= 31,314, Lumbar Spinal Stenosis
n
= 53,043 and Degenerative Disc Disease
n
= 14,375). The proportion reaching the minimal important change (MIC) in Visual Analogue Scale for pain (VAS
BACK/LEG
), Oswestry Disability Index (ODI) and the quality-of-life measure EQ-5D
INDEX
at 1 and 2 years, respectively, was calculated. The single-item questions such as Global Assessment (GA
BACK/LEG
) and Satisfaction were analysed by the McNemar test. Threshold values for a successful outcome based on the final scores of each PROM at 1 and 2 years post-surgery were also defined.
Results
For all the three diagnostic groups, the differences in proportions reaching MIC of each PROM at 1 and 2 years were below 2%. Global Assessment and Satisfaction with outcome at one year remained at 2 years. There were no important differences of threshold values of treatment success based on final scores
Conclusion
No clinically important changes in PROMs appeared between 1 and 2 years after surgery for degenerative lumbar conditions, demonstrating that a follow-up period of 1 year as opposed to 2 years is sufficient in effectiveness studies if PROMs are to be used as outcome variables.
Graphical abstract
These slides can be retrieved under Electronic Supplementary Material.
Purpose
There are two, principally different ways to obtain patient opinions regarding the outcome of spine surgery: using prospective multi-item questionnaires preoperatively and at follow-up, and ...using a retrospective single-item question at follow-up—both methods have distinct advantages and limitations. The purpose of the study was to explore the utility of using the simple transition question global assessment, GA, (“How is your back/leg pain today as compared to before the surgery?”) as an overall patient-reported outcome measure (PROM) based on the large real-life database in the Swedish spine registry (Swespine).
Methods
The correlation between GA and the score-changes and the final scores at 1 year of follow-up for the PROMs VAS, ODI, and EQ-5D was examined. The correlations between GA and item-specific domains within the ODI, EQ-5D and SF-36 as well as the discriminative ability of PROMs with GA as reference criterion were also analysed. The cohort consisted of 94,132 patients registered in Swespine who were surgically treated for disc herniation, spinal stenosis or degenerative disc disease.
Results
The correlation coefficients for GA vs. the score-changes were lower than for GA vs final scores. For VAS they ranged for the different diagnosis groups from 0.33 to 0.61 and from 0.50 to 0.79, respectively. For ODI, the corresponding values ranged from 0.43 to 0.65 and 0.63 to 0.76; for the EQ-5D from 0.32 to 0.45 and 0.54 to 0.71. Further, GA showed a somewhat stronger correlation to pain-specific PROMs than to quality-of-life PROMs.
Conclusions
The single-item outcome measure global assessment (GA) appears to be a feasible overall patient-reported outcome measure (PROM) and a useful reference for interpreting the scores of patient-reported outcome measures.
Purpose
The relatively large number of participants lost to follow-up (attrition) in spinal registers calls for studies that investigate the features of these individuals and their possible outcome. ...The aim was to explore the effect of attrition on patient-reported outcome in patients undergoing degenerative lumbar spine surgery. Three groups were studied: spinal stenosis (LSS), disc herniation (LDH) and degenerative disc disorder (DDD).
Methods
Patients who underwent surgery for degenerative lumbar spine conditions during 2008–2012 according to registration in the Swespine national register were eligible for the study. Non-respondents were registered in Swespine prior to surgery, but not at follow-up. Swespine data were merged with hospital data from seven Swedish regions (65% of the population), Statistics Sweden, the National Patient Register and the Social Insurance Agency.
Baseline characteristics of non-respondents were described and compared to those of the respondents. Coefficients from regression analyses on PROM values for respondents were used to estimate the levels of PROM values for non-respondents, assuming the same effects of baseline characteristics for the two subgroups. Regression analyses were then conducted to identify variables associated with non-response. The results from the regression analyses were used to predict outcomes for patients with the characteristics of a non-respondent. Primary outcome variable in LSS and LDH was Global Assessment for leg pain, and in DDD, Global Assessment for back pain.
Results
Age, sex, educational level, smoking, living alone, being born outside the EU, previous spine surgery and unexpected events before follow-up were factors that were significantly associated with non-response. Being born inside, the EU was important in all of the studied groups (LSS: OR 0.61
p
= < 0.000; LDH: OR 0.68
p
= 0.001; DDD: OR 0.58
p
= 0.04). For spinal stenosis patients, an unexpected event appeared particularly important (OR 3.40,
p
= 0.000). The predicted outcome of non-respondents was significantly worse than for respondents (LSS: 75.4% successful outcome vs. 78.7%; LDH: 53.9% vs. 58.2%; DDD: 62.7% vs. 67.5%. P-value in all groups = < 0.000).
Conclusion
Attrition in Swespine cannot be ignored, as non-respondents were predicted to have worse outcome. The effect of attrition bias should always be considered when contemplating outcome recorded in a quality register with patients lost to follow-up.
•Different methods to determine unburned carbon in ash yield slightly different results.•Unburned carbon is mostly elemental carbon, very little volatile or semi-volatile organic carbon.•Raman ...results show that unburned carbon is similar in bottom ash and in fly ash.
Unburned carbon (UC) in 21 combustion residues from solid biofuels has been examined using several methods of analysis (including LOI and TOC) as well as micro-Raman spectroscopy. The concentration of unburned carbon in the residues varied over an order of magnitude and in several samples accounted for about 10% of the ash mass. It was observed that TOC had a poor correlation to organic carbon, especially for fly ashes. LOI at all tested temperatures showed a better correlation than TOC to the organic carbon content, whereas the TOC is better correlated to elemental carbon. LOI550 gave a larger variation and a less complete mobilisation of unburned carbon than LOI at 750 or 975°C did, but at the highest temperature metal oxidation was notably affecting the mass balance to the extent that some samples gained mass. For this reason, and of the temperatures tested, LOI750 seem to be the most stable indicator for organic remains in the incineration residuals. Most of the unburned carbon is elemental, and only slowly degradable, so the potential emissions of organic compounds from ashes should not be assessed by using a TOC test. The structure of the detected elemental carbon in UC is similar to that of activated carbon, which indicates a potentially large specific surface. This should be borne in mind when assessing the environmental impact of using ash for different purposes, including use as a construction material. Field studies are needed to verify the actual impact as it may depend on environmental conditions.
Vegetation buffers local diurnal land surface temperatures, however, this effect has found limited applications for remote vegetation characterization. In this work, we parameterize diurnal ...temperature variations as the thermal decay rate derived by using satellite daytime and nighttime land surface temperatures and modeled using Newton's law of cooling. The relationship between the thermal decay rate and vegetation depends on many factors including vegetation type, size, water content, location, and local conditions. The theoretical relationships are elucidated, and empirical relationships are presented. Results show that the decay rate summarizes both vegetation structure and function and exhibits a high correlation with other established vegetation-related observations. As proof of concept, we interpret 15-year spatially explicit trends in the annual thermal decay rates over Africa and discuss results. Given recent increases in availability of finer spatial resolution satellite thermal measurements, the thermal decay rate may be a useful index for monitoring vegetation.
STUDY DESIGN.Prospective randomized controlled trial.
OBJECTIVE.To study the outcome of anterior cervical decompression and fusion combined with a structured physiotherapy program compared with the ...same physiotherapy program alone for patients with cervical radiculopathy.
SUMMARY OF BACKGROUND DATA.Knowledge concerning the effects of interventions for patients with cervical radiculopathy is scarce due to a lack of randomized studies.
METHODS.Sixty-three patients were randomized to surgery with postoperative physiotherapy (n = 31) or physiotherapy alone (n = 32). The surgical group was treated with anterior cervical decompression and fusion. The physiotherapy program included general/specific exercises and pain-coping strategies. The outcome measures were disability (Neck Disability Index), neck and arm pain intensity (visual analogue scale), and the patientʼs global assessment. Patients were followed for 24 months.
RESULTS.The result from the repeated-measures analysis of variance showed no significant between-group difference for Neck Disability Index (P = 0.23). For neck pain intensity, the repeated-measures analysis of variance showed a significant between-group difference during the study period in favor of the surgical group (P = 0.039). For arm pain intensity, no significant between-group differences were found according to the repeated-measures analysis of variance (P = 0.580). Eighty-seven percent of the patients in the surgical group rated their symptoms as “better/much better” at the 12-month follow-up compared with 62% in the nonsurgical group (P < 0.05). At 24 months, the corresponding figures were 81% and 69% (P = 0.28). The difference was significant only at the 12-month follow-up in favor of the surgical group. Significant reduction in Neck Disability Index, neck pain, and arm pain compared with baseline was seen in both groups (P < 0.001).
CONCLUSION.In this prospective, randomized study of patients with cervical radiculopathy, it was shown that surgery with physiotherapy resulted in a more rapid improvement during the first postoperative year, with significantly greater improvement in neck pain and the patientʼs global assessment than physiotherapy alone, but the differences between the groups decreased after 2 years. Structured physiotherapy should be tried before surgery is chosen.Level of Evidence2
Purpose
A statistically significant score change of a PROM (Patient-Reported Outcome Measure) can be questioned if it does not exceed the clinically Minimal Important Change (MIC) or the SDC ...(Smallest Detectable Change) of the particular measure. The aim of the study was to define the SDC of three common PROMs in degenerative lumbar spine surgery: Numeric Rating Scale (NRS
BACK/LEG
), Oswestry Disability Index (ODI) and Euroqol-5-Dimensions (EQ-5D
INDEX
) and to compare them to their MICs. The transition questions Global Assessment (GA
BACK/LEG
) were also explored.
Methods
Reliability analyses were performed on a test–retest population of 182 symptomatically stable patients, with similar characteristics as the Swespine registry population, who underwent surgery for degenerative lumbar spine conditions 2017–2018. The MIC values were based on the entire registry (
n
= 98,732) using the ROC curve method. The ICC for absolute agreement was calculated in a two-way random-effects single measures model. For categorical variables, weighted kappa and exact agreement were computed.
Results
For the NRS, the SDC exceeded the MIC (NRS
BACK
:3.6 and 2.7; NRS
LEG
: 3.7 and 3.2, respectively), while they were of an equal size of 18 for the ODI. The gap between the two estimates was remarkable in the EQ-5D
INDEX
, where SDC was 0.49 and MIC was 0.10. The GA
BACK/LEG
showed an excellent agreement between the test and the retest occasion.
Conclusion
For the tested PROM scores, the changes must be considerable in order to distinguish a true change from random error in degenerative lumbar spine surgery research.
Graphic abstract
These slides can be retrieved under Electronic Supplementary Material.
Aims
To investigate, in a large population in primary care, the relationship between fasting plasma glucose and HbA1c measurements, as well as the clinical implications of anaemia or chronic kidney ...disease for the interpretation of HbA1c values.
Methods
From a primary care resource, we examined HbA1c and fasting plasma glucose as well as haemoglobin and estimated GFR. We stratified observations by chronic kidney disease stage and anaemia level. The estimation of the mean fasting plasma glucose level from HbA1c alone, and from HbA1c, haemoglobin and estimated GFR, respectively, was evaluated.
Results
In 198 346 individuals, the fasting plasma glucose–HbA1c relationship mimicked the regression described in the A1c‐Derived Average Glucose (ADAG) study, which was based on average capillary and interstitial glucose. The fasting plasma glucose–HbA1c relationship was unaffected in mild to moderate chronic kidney disease and in mild to moderate anaemia. The correlation changed only in severe hyperglycaemia and concurrent severe anaemia or when estimated GFR was <45 ml/min/1.73m², so that glucose concentration was underestimated by HbA1c in anaemia and overestimated in chronic kidney disease. The prevalence of estimated GFR <30 ml/min/1.73m² was 0.82%, while the prevalence of haemoglobin <81 g/l (5.0 mmol/l) was 0.11%.
Conclusions
The relationship between fasting plasma glucose and HbA1c mimics that of the people with diabetes included in the ADAG study. Mild to moderate anaemia and CKD do not have a significant impact on the interpretation of HbA1c as a marker of retrograde glycaemia. Hence, it seems justified to use HbA1c without adjustment in primary care.
What's new?
The clinical implications of anaemia and chronic kidney disease with regard to the interpretation of HbA1c are not well described.
In a large primary care population, mild to moderate anaemia or mild to moderate chronic kidney disease do not have a significant impact on the relationship between glycaemia and HbA1c.
HbA1c can be used to assess glycaemic control in primary care.
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