The Alkmaar CTO Registry: A Retrospective Cohort Evaluating the Introduction of a Dedicated CTO Program.

BACKGROUND: Percutaneous coronary interventions (PCI) of chronic total occlusions (CTO) are high risk procedures with low success rates compared to standard PCI. Recently the 'hybrid approach' method has been developed to increase success rate. In 2015 we set up a dedicated program to systematically treat CTOs by this hybrid approach. This retrospective, observational registry aims to report achieved results in a single PCI centre. METHODS AND RESULTS: We reviewed all CTO procedures between January 2012 and December 2017. Procedures performed by dedicated operators after December 2014 were assigned to the hybrid cohort, procedures done before this time or performed by a non-CTO operator were assigned to the non-hybrid cohort. Procedural techniques, difficulty of lesions, J-CTO scores, outcomes and complications were analysed. In total 505 procedures were included. Average J-CTO score was 1.9 ± 1.1, which was significantly higher in the hybrid cohort (2.1 ± 1.2 vs. 1.6 ± 1.1; p < 0.001). Overall procedural success rate was 75.4% with significantly higher success rates in the hybrid cohort (81.2% vs. 68.2%; p < 0.001). Combining both cohorts, overall success rate increased over the years (2012-2017 respectively 65.2%, 60.0%, 71.7%, 83.2%, 77.9% and 81.4%). Complication rate was higher in the hybrid cohort compared to the non-hybrid cohort (4.6% vs 0.4%, respectively; p = 0.026). CONCLUSION: By introducing a systematic CTO program, including use of the hybrid approach, we observed higher success rates of PCI CTO, despite increased complexity of the lesions (higher J-CTO score). The occurrence of MACE was in accordance with current literature. CONDENSED ABSTRACT: Our registry demonstrates that introduction of a dedicated CTO program increases success rates of CTO treatments despites increased lesions difficulty and with acceptable MACEs rates.

HPV Prevalence in the Dutch cervical cancer screening population (DuSC study): HPV testing using automated HC2, cobas and Aptima workflows.

BACKGROUND: Primary high risk (hr)HPV screening will be introduced in The Netherlands in January 2017. Our aim was to determine the hrHPV prevalence in the Dutch cervical cancer screening population (DuSC study). METHODS: A total of 12,113 residual PreservCyt cervical samples from the Dutch population based cytology screening program were rendered anonymous, randomized and tested for hrHPV using 3 HPV assays on their respective automated platforms: QIAGEN's digene® HC2 HPV DNA Test® (HC2, signal amplification), Roche Cobas® HPV test (DNA amplification) and Hologic Aptima® HPV Test (RNA amplification). To determine the agreement between results generated using the different assays, pair wise comparison of the systems was performed by determining kappa coefficients. RESULTS: The selected samples were representative for the population based screening program with respect to age distribution and cytology classification. HrHPV prevalences found were: 8.5% for HC2 (n = 959), 8.1% for cobas (n = 919) and 7.5% for Aptima (n = 849), resulting in a mean hrHPV prevalence of 8.0 ± 0.5%. Although the hrHPV prevalences of the different assays are in the range of 8%, there was a significant difference in prevalence for the HC2 vs. Aptima assay (p-value = 0.007). A clear age dependency was found, with an hrHPV prevalence ranging from 18.7 ± 1.2% in women 29-33 years of age to 4.2 ± 0.2% in women 59-63 years of age. Furthermore, a correlation between hrHPV prevalence and severity of cytology was observed, ranging from 5.5 ± 0.4% in normal cytology to 95.2 ± 1.7% in severe dysplasia. Indeed, kappa coefficients of 0.77, 0.71 and 0.72 (HC2 vs cobas, cobas vs Aptima and Aptima vs HC2, respectively) indicated substantial agreement between the results generated by the different systems. However, looking at the hrHPV positive samples, only 48% of the samples tested positive with all 3 assays. CONCLUSIONS: A hrHPV prevalence of 8% was found in this unselected population based screening cohort independently of using HC2, Aptima or cobas. This prevalence is higher than the previously reported 4-5% (POBASCAM and VUSA-Screen trials). Furthermore, the complete automated hrHPV detection workflow solutions from QIAGEN, Roche, and Hologic were successfully used and will be valuable for reliably implementing high throughput hrHPV testing in cervical cancer screening.

Rev1 is essential in generating G to C transversions downstream of the Ung2 pathway but not the Msh2+Ung2 hybrid pathway.

Somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin (Ig) genes are initiated by the enzymatic deamination of cytosine (C) to uracil (U). Uracil-DNA-glycosylase (Ung2) converts uracils into apyrimidinic (AP) sites, which is essential for the generation of transversions (TVs) at G/C basepairs during SHM and for efficient DNA break formation during CSR. Besides Ung2, the mismatch repair protein Msh2 and the translesion synthesis (TLS) DNA polymerase (Pol) Rev1 are implicated in SHM and CSR. To further unravel the role of Rev1, we studied WT, Rev1-deficient, Msh2-deficient, and Rev1, Msh2 double-deficient B cells. Loss of Rev1 only slightly reduced CSR. During SHM G/C to C/G TVs are generated in both Ung2- and Ung+Msh2-dependent fashions. We found that Rev1 is essential for the Msh2-independent generation of these TVs downstream of Ung2-induced AP sites. In the Ung+Msh2 hybrid pathway, Rev1 is not essential and can be substituted by an alternative TLS Pol, especially when Rev1 is lacking.

Propranolol, a very promising treatment for ulceration in infantile hemangiomas: a study of 20 cases with matched historical controls.

BACKGROUND: Ulceration is a common but poorly understood complication of infantile hemangiomas (IH) that is difficult to control. OBJECTIVE: To investigate the possible role of monotherapy with propranolol for ulcerating IH. METHODS: Propranolol was given to 20 patients with IH, who suffered from ulceration at the start of treatment (mean age at onset of treatment, 3.5 months; standard error of the mean: 0.4). After cardiac screening, propranolol was administered in a progressive schedule to 2 to 2.5 mg/kg per day, divided in 3 doses. Blood pressure, heart rate, and fasting glucose levels were monitored during the first 3 days in hospital and, in the absence of complications, treatment was continued at home until the age of approximately 1 year. The 20 propranolol-treated patients were matched to patients from a historical control group, seen before the 'propranolol era'. These matches were randomly made by using clinical pictures based on type, location and size of the IH, extent of ulceration, and age at the start of ulceration. RESULTS: The time to complete healing from the onset of ulceration was significantly shorter for the propranolol-treated patients, compared with the control group (8.7 vs 22.4 weeks; t test: P < .015). In the propranolol group, a tendency to shorter ulceration duration was seen in patients starting propranolol at an earlier stage of disease. LIMITATIONS: The study was limited by the partially retrospective design and the small number of patients. CONCLUSION: Propranolol reduces the duration of ulceration in IH and seems to be more effective when started in an early phase. We propose propranolol as the treatment of first choice for ulcerating IH.

Differences between ulcerated and non-ulcerated hemangiomas, a retrospective study of 465 cases.

Our purpose was to get better insight into the ulceration of hemangiomas, by comparing patient characteristics of non-ulcerated hemangiomas with hemangiomas with active or past ulceration. A retrospective analysis was performed of files of patients who visited the Radboud University Medical Centre Nijmegen (UMCN), the Netherlands, between 1997 and 2007 for one or more infantile hemangiomas. The medical records of 465 patients were reviewed. Twenty three percent of the patients were diagnosed with ulceration. The size of ulcerated hemangiomas was significantly larger (28.6 cm2 vs. 6.0 cm2, p < 0.05). Predilection areas for ulceration were the head-neck region and the anogenital region. Ulceration was significantly most frequently seen in hemangiomas with a superficial (epidermal) component (98.5%, p < 0.05) and a segmental distribution (29.3%, p < 0.05). Ulceration most frequently took place during the proliferation phase of the hemangioma (83.1%). In the whole study population the male to female ratio was 1:2 compared to a tendency to more girls (1:3) for the group with ulcerated hemangiomas (p = 0.08). We conclude that larger, more superficial hemangiomas in areas more susceptible to trauma and contamination were more likely to ulcerate. This study contributes to the possibility of assessing the likelihood of ulceration in an individual patient.