The sentinel node biopsy has not come of age Sladden, M.; Zagarella, S.; Popescu, C. ...
British journal of dermatology (1951),
February 2020, 2020-Feb, 2020-02-00, 20200201, Letnik:
182, Številka:
2
Journal Article
Recenzirano
Linked Article: McGregor et al. Br J Dermatol 2019; 181:423.
The endothelial glycocalyx, a sieve-like structure located on the luminal surface of all blood vessels, has been found to be integral to regulation of capillary permeability and mechanotransduction. ...Given this, we investigated the role of endothelial glycocalyx breakdown products in organ donors and recipients in terms of acceptability for transplant and risk of primary graft dysfunction (PGD).
Endothelial glycocalyx breakdown products were measured in the peripheral blood of 135 intended and actual organ donors. Breakdown product levels were tested for association with donor demographic and clinical data, organ acceptability for transplant along with lung recipient outcomes (n = 35). Liquid chromatography mass spectrometry analysis was performed to confirm glycosaminoglycan levels and sulfation patterns on donor samples (n = 15). In transplant recipients (n = 50), levels were measured pretransplant and daily for 4 days posttransplant. Levels were correlated with PGD severity and intubation time.
Decreased hyaluronan levels in peripheral blood independently predicted organ acceptability in intended and actual donors (odds ratio, 0.96; 95% confidence interval, 0.93-0.99 P = 0.026). Furthermore, high donor syndecan-1 levels were associated with PGD in recipients (3142 1575-4829 versus 6229 4009-8093 pg/mL; P = 0.045). In recipient blood, levels of syndecan-1 were correlated with severe (grades 2-3) PGD at 72 hours posttransplant (5982 3016-17191 versus 3060 2005-4824 pg/mL; P = 0.01).
Endothelial glycocalyx breakdown occurs in lung transplant donors and recipients and predicts organ acceptability and development of PGD. Glycocalyx breakdown products may be useful biomarkers in transplantation, and interventions to protect the glycocalyx could improve transplant outcomes.
Summary
Background
Sentinel lymph node biopsy (SLNB) was developed in the hope that it would improve outcomes for patients with melanoma. SLNB is an area of discussion and controversy in melanoma ...medicine. The final trial results of the Multicenter Selective Lymphadenectomy Trial (MSLT‐I) have now been published and the authors suggest their long‐term results ‘clearly validate the use of sentinel‐node biopsy in patients with intermediate‐thickness or thick primary melanomas’. An accompanying editorial states that MSLT‐I is a practice‐changing trial.
Conclusions
However, critical appraisal of MSLT‐I data does not support the claims of the final report. On the contrary, MSLT‐I failed to demonstrate that there is a significant treatment‐related difference in the 10‐year melanoma‐specific survival rate in the overall study population. Furthermore, there was no improvement in overall or melanoma‐specific survival of the intermediate‐thickness group (1·2–3·5 mm). Completion lymphadenectomy can result in complications in about a third of patients, with a rate of clinically significant lymphoedema following axillary or groin dissection of 5–10%. Unnecessary lymphadenectomy can therefore have a major effect on patient quality of life. The evidence provided by Morton et al. does not support the claim that sentinel lymph node biopsy followed by lymphadenectomy in patients with positive sentinel nodes should be the standard of care in patients with melanoma. Readers are encouraged to check with registration sites to make sure declared primary outcomes are fairly reported. Post‐hoc analyses are at best exploratory and cannot be used to form the principal conclusions of a trial.
Background
Breslow thickness, patient age and ulceration are the three most valuable clinical and pathological predictors of melanoma survival. A readily available reliable online tool that ...accurately considers these and other predictors could be valuable for clinicians managing melanoma patients.
Objective
To compare online melanoma survival prediction tools that request user input on clinical and pathological features.
Methods
Search engines were used to identify available predictive nomograms. For each, clinical and pathological predictors were compared.
Results
Three tools were identified. The American Joint Committee on Cancer tool inappropriately rated thin tumours as higher risk than intermediate tumours. The University of Louisville tool was found to have six shortcomings: a requirement for sentinel node biopsy, unavailable input of thin melanoma or patients over 70 years of age and less reliable hazard ratio calculations for age, ulceration and tumour thickness. The LifeMath.net tool was found to appropriately consider tumour thickness, ulceration, age, sex, site and tumour subtype in predicting survival.
Limitations
The authors did not have access to the base data used to compile various prediction tools.
Conclusion
The LifeMath.net prediction tool is the most reliable for clinicians in counselling patients with newly diagnosed primary cutaneous melanoma regarding their survival prospects.
Erratic tacrolimus blood levels are associated with liver and kidney graft failure. We hypothesized that erratic tacrolimus exposure would similarly compromise lung transplant outcomes. This study ...assessed the effect of tacrolimus mean and standard deviation (SD) levels on the risk of chronic lung allograft dysfunction (CLAD) and death after lung transplantation.
We retrospectively reviewed 110 lung transplant recipients who received tacrolimus-based immunosuppression. Cox proportional hazard modeling was used to investigate the effect of tacrolimus mean and SD levels on survival and CLAD. At census, 48 patients (44%) had developed CLAD and 37 (34%) had died.
Tacrolimus SD was highest for the first 6 post-transplant months (median, 4.01; interquartile range IQR, 3.04-4.98 months) before stabilizing at 2.84 μg/liter (IQR, 2.16-4.13 μg/liter) between 6 and 12 months. The SD then remained the same (median, 2.85; IQR, 2.00-3.77 μg/liter) between 12 and 24 months. A high mean tacrolimus level 6 to 12 months post-transplant independently reduced the risk of CLAD (hazard ratio HR, 0.74; 95% confidence interval CI, 0.63-0.86; p < 0.001) but not death (HR, 0.96; 95% CI, 0.83-1.12; p = 0.65). In contrast, a high tacrolimus SD between 6 and 12 months independently increased the risk of CLAD (HR, 1.46; 95% CI, 1.23-1.73; p < 0.001) and death (HR, 1.27; 95% CI, 1.08-1.51; p = 0.005).
Erratic tacrolimus levels are a risk factor for poor lung transplant outcomes. Identifying and modifying factors that contribute to this variability may significantly improve outcomes.
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