Increase of sentinel lymph node melanoma staging in The Netherlands; still room and need for further improvement

Aim: To investigate implementation of the seventh American Joint Committee on Cancer melanoma staging with sentinel lymph node biopsy (SLNB) and associations with socioeconomic status (SES). Patients & methods: Data from The Netherlands Cancer Registry on patient and tumor characteristics were analyzed for all stage IB-II melanoma cases diagnosed 2010-2016, along with SES data from The Netherlands Institute for Social Research. Results: The proportion of SLNB-staged patients increased from 40% to 65% (p <0.001). Multivariate analysis showed that being female, elderly, or having head-and-neck disease reduced the likelihood of SLNB staging. Conclusion: SLNB staging increased by 25% during the study period but lagged among elderly patients and those with head-and-neck melanoma. In The Netherlands, SES no longer affects SLNB staging performance

Locked-In Syndrome after Traumatic Basilar Artery Entrapment within a Clivus Fracture:A Case Report and Review of the Literature

We report the case of a 58-year-old male with a rare vascular complication after traumatic head injury: entrapment of the basilar artery into a fracture of the clivus, ultimately leading to a locked-in syndrome due to brainstem infarction. Review of the literature revealed 19 earlier published cases of basilar artery entrapment within traumatic longitudinal clival fractures. In the majority of these patients there is an unfavorable neurological outcome

One-Year Morbidity Following Videoscopic Inguinal Lymphadenectomy for Stage III Melanoma

Simple Summary Inguinal lymphadenectomy (the removal of lymph nodes in the groin) is currently part of the treatment options for stage III melanoma patients. Surgery can be performed using one large inguinal incision (open approach) or a few smaller incisions (videoscopic approach). Previous research has already shown less severe complications and comparable oncologic outcomes after the videoscopic approach. Postoperative lymphedema following inguinal lymphadenectomy is a well-known problem which can potentially decrease quality of life. With the arrival of adjuvant systemic treatment options, less invalidating surgery is highly desirable. However, lymphedema and quality of life have only been investigated after the open approach. Therefore, we evaluated lymphedema and quality of life following videoscopic inguinal lymphadenectomy for stage III melanoma. The videoscopic inguinal lymphadenectomy is a feasible approach due to the comparable lymphedema incidence and normalization of quality of life during follow-up. Purpose: We aimed to elucidate morbidity following videoscopic inguinal lymphadenectomy for stage III melanoma. Methods: Melanoma patients who underwent a videoscopic inguinal lymphadenectomy between November 2015 and May 2019 were included. The measured outcomes were lymphedema and quality of life. Patients were reviewed one day prior to surgery and postoperatively every 3 months for one year. Results: A total number of 34 patients were included for participation; 19 (55.9%) patients underwent a concomitant iliac lymphadenectomy. Lymphedema incidence was 40% at 3 months and 50% at 12 months after surgery. Mean interlimb volume difference increased steadily from 1.8% at baseline to 6.9% at 12 months (p = 0.041). Median Lymph-ICF-LL total score increased from 0.0 at baseline to 12.0 at 3 months, and declined to 8.5 at 12 months (p = 0.007). Twelve months after surgery, Lymph-ICF-LL scores were higher for females (p = 0.021) and patients that received adjuvant radiotherapy (p = 0.013). The Median Distress Thermometer and EORTC QLQ-C30 summary score recovered to baseline at 12 months postoperatively (p = 0.747 and p = 0.203, respectively). Conclusions: The onset of lymphedema is rapid and continues to increase up to one year after videoscopic inguinal lymphadenectomy. Quality of life recovers to the baseline value

The MELFO Study:A Multicenter, Prospective, Randomized Clinical Trial on the Effects of a Reduced Stage-Adjusted Follow-Up Schedule on Cutaneous Melanoma IB-IIC Patients-Results After 3 Years

Background This study compares well-being, recurrences, and deaths of early-stage cutaneous melanoma patients in follow-up, as recommended in the Dutch guideline, with that of patients in a stage-adjusted reduced follow-up schedule, 3 years after diagnosis, as well as costs. Methods Overall, 180 eligible pathological American Joint Committee on Cancer (AJCC) stage IB-IIC, sentinel node staged, melanoma patients (response rate = 87%, 48% male, median age 57 years), randomized into a conventional (CSG, n = 93) or experimental (ESG, n = 87) follow-up schedule group, completed patient-reported outcome measures (PROMs) at diagnosis (T1): State-Trait Anxiety Inventory-State version (STAI-S), Cancer Worry Scale (CWS), Impact of Event Scale (IES), and RAND-36 (Mental and Physical Component scales [PCS/MCS]). Three years later (T3), 110 patients (CSG, n = 56; ESG, n = 54) completed PROMs, while 42 declined (23%). Results Repeated measures analyses of variance (ANOVAs) showed a significant group effect on the IES (p = 0.001) in favor of the ESG, and on the RAND-36 PCS (p = 0.02) favoring the CSG. Mean IES and CWS scores decreased significantly over time, while those on the RAND-36 MCS and PCS increased. Effect sizes were small. Twenty-five patients developed a recurrence or second primary melanoma, of whom 13 patients died within 3 years. Cox proportional hazards models showed no differences between groups in recurrence-free survival (hazard ratio [HR] 0.71 [0.32-1.58]; p = 0.400) and disease-free survival (HR 1.24 [0.42-3.71]; p = 0.690). Costs per patient after 3 years (computed for 77.3% of patients) were 39% lower in the ESG. Conclusion These results seemingly support the notion that a stage-adjusted reduced follow-up schedule forms an appropriate, safe, and cost-effective alternative for pathological AJCC stage IB-IIC melanoma patients to the follow-up regimen as advised in the current melanoma guideline

Systematic adjudication of myocardial infarction end-points in an international clinical trial

BACKGROUND: Clinical events committees (CEC) are used routinely to adjudicate suspected end-points in cardiovascular trials, but little information has been published about the various processes used. We reviewed results of the CEC process used to identify and adjudicate suspected end-point (post-enrolment) myocardial infarction (MI) in the large Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial. METHODS: The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. A central adjudication process was established prospectively to identify all suspected MIs and adjudicate events based on protocol definitions of MI. Suspected MIs were identified by systematic review of data collection forms, cardiac enzyme results, and electrocardiograms. Two physicians independently reviewed all suspected events. If they disagreed whether a MI had occurred, a committee of cardiologists adjudicated the case. RESULTS: The CEC identified 5005 patients with suspected infarction (46%), of which 1415 (28%) were adjudicated as end-point infarctions. As expected, the process identified more end-point events than did the site investigators. Absolute and relative treatment effects of eptifibatide were smaller when using CEC-determined MI rates rather than site investigator-determined rates. The site-investigator reporting of MI and the CEC assessment of MI disagreed in 20% of the cases reviewed by the CEC. CONCLUSIONS: End-point adjudication by a CEC is important, to provide standardised, systematic, independent, and unbiased assessment of end-points, particularly in trials that span geographic regions and clinical practice settings. Understanding the CEC process used is important in the interpretation of trial results and event rates

Disagreements between central clinical events committee and site investigator assessments of myocardial infarction endpoints in an international clinical trial: review of the PURSUIT study

BACKGROUND: Limited information has been published regarding how specific processes for event adjudication can affect event rates in trials. We reviewed nonfatal myocardial infarctions (MIs) reported by site investigators in the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial and those adjudicated by a central clinical events committee (CEC) to determine the reasons for differences in event rates. METHODS: The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. The primary end-point was death or post-enrolment MI at 30 days as assessed by the CEC; this end-point was also constructed using site-reported events. The CEC identified suspected MIs by systematic review of clinical, cardiac enzyme, and electrocardiographic data. RESULTS: The CEC identified 5005 (46%) suspected events, of which 1415 (28%) were adjudicated as MI. The site investigator and CEC assessments of whether a MI had occurred disagreed in 983 (20%) of the 5005 patients with suspected MI, mostly reflecting site misclassification of post-enrolment MIs (as enrolment MIs) or underreported periprocedural MIs. Patients for whom the CEC and site investigator agreed that no end-point MI had occurred had the lowest mortality at 30 days and between 30 days and 6 months, and those with agreement that a MI had occurred had the highest mortality. CONCLUSION: CEC adjudication provides a standard, systematic, independent, and unbiased assessment of end-points, particularly for trials that span geographic regions and clinical practice settings. Understanding the review process and reasons for disagreement between CEC and site investigator assessments of MI is important to design future trials and interpret event rates between trials

Candidate Gene Analysis of Femoral Neck Trabecular and Cortical Volumetric Bone Mineral Density in Older Men

In contrast to conventional dual-energy X-ray absorptiometry, quantitative computed tomography separately measures trabecular and cortical volumetric bone mineral density (vBMD). Little is known about the genetic variants associated with trabecular and cortical vBMD in humans, although both may be important for determining bone strength and osteoporotic risk. In the current analysis, we tested the hypothesis that there are genetic variants associated with trabecular and cortical vBMD at the femoral neck by genotyping 4608 tagging and potentially functional single-nucleotide polymorphisms (SNPs) in 383 bone metabolism candidate genes in 822 Caucasian men aged 65 years or older from the Osteoporotic Fractures in Men Study (MrOS). Promising SNP associations then were tested for replication in an additional 1155 men from the same study. We identified SNPs in five genes (IFNAR2, NFATC1, SMAD1, HOXA, and KLF10) that were robustly associated with cortical vBMD and SNPs in nine genes (APC, ATF2, BMP3, BMP7, FGF18, FLT1, TGFB3, THRB, and RUNX1) that were robustly associated with trabecular vBMD. There was no overlap between genes associated with cortical vBMD and trabecular vBMD. These findings identify novel genetic variants for cortical and trabecular vBMD and raise the possibility that some genetic loci may be unique for each bone compartment. © 2010 American Society for Bone and Mineral Researc

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention