First generation versus second generation drug-eluting stents for the treatment of bifurcations: 5-year follow-up of the LEADERS all-comers randomized trial.

BACKGROUND Historically, percutaneous coronary intervention (PCI) of bifurcation lesions was associated with worse procedural and clinical outcomes when compared with PCI of non-bifurcation lesions. Newer generation drug-eluting stents (DES) might improve long-term clinical outcomes after bifurcation PCI. METHODS AND RESULTS The LEADERS trial was a 10-center, assessor-blind, non-inferiority, all-comers trial, randomizing 1,707 patients to treatment with a biolimus A9(TM) -eluting stent (BES) with an abluminal biodegradable polymer or a sirolimus-eluting stent (SES) with a durable polymer (ClinicalTrials.gov Identifier: NCT00389220). Five-year clinical outcomes were compared between patients with and without bifurcation lesions and between BES and SES in the bifurcation lesion subgroup. There were 497 (29%) patients with at least 1 bifurcation lesion (BES = 258; SES = 239). At 5-year follow-up, the composite endpoint of cardiac death, myocardial infarction (MI) and clinically-indicated (CI) target vessel revascularization (TVR) was observed more frequently in the bifurcation group (26.6% vs. 22.4%, P = 0.049). Within the bifurcation lesion subgroup, no differences were observed in (cardiac) death or MI rates between BES and SES. However, CI target lesion revascularization (TLR) (10.1% vs. 15.9%, P = 0.0495), and CI TVR (12.0% vs. 19.2%, P = 0.023) rates were significantly lower in the BES group. Definite/probable stent thrombosis (ST) rate was numerically lower in the BES group (3.1% vs. 5.9%, P = 0.15). Very late (>1 year) definite/probable ST rates trended to be lower with BES (0.4% vs. 3.1%, P = 0.057). CONCLUSIONS In the treatment of bifurcation lesions, use of BES led to superior long-term efficacy compared with SES. Safety outcomes were comparable between BES and SES, with an observed trend toward a lower rate of very late definite/probable ST between 1 and 5 years with the BES. © 2015 Wiley Periodicals, Inc.

DESyne novolimus-eluting coronary stent is superior to Endeavor zotarolimus-eluting coronary stent at five-year follow-up: final results of the multicentre EXCELLA II randomised controlled trial

AIMS Newer-generation drug-eluting stents (DES) have been shown to be superior to first-generation DES. Current-generation DES have zotarolimus, everolimus or biolimus as antiproliferative drugs. Novolimus, a metabolite of sirolimus, has been specifically developed to provide efficacy similar to currently available agents at a lower dose and thus requires a lower polymer load. We report the final five-year outcomes of the EXCELLA II trial comparing a zotarolimus-eluting stent (ZES) with a novolimus-eluting stent (NES). METHODS AND RESULTS EXCELLA II is a prospective, multicentre, single-blind, non-inferiority clinical trial. Patients (n=210) with a maximum of two de novo lesions in two different epicardial vessels were randomised (2:1) to treatment with either NES (n=139) or ZES (n=71). At five-year follow-up, patients in the NES group had a significantly lower incidence of the patient-oriented (HR 0.53, 95% CI: 0.32-0.87, p=0.013) and device-oriented (HR 0.38, 95% CI: 0.17-0.83, p=0.011) composite endpoints. There was no difference in cardiac death and definite/probable stent thrombosis between the two groups; however, there was a trend towards reduction in myocardial infarction and repeat revascularisation in the NES group at five-year follow-up. CONCLUSIONS At five-year follow-up, the incidence of device- and patient-oriented events was significantly lower in the NES group. Further studies, adequately powered for clinical outcomes, are warranted. TRIAL REGISTRATION ClinicalTrials.gov number NCT00792753.

Prognostic markers in lentigo maligna patients treated with imiquimod cream: A long-term follow-up study.

BACKGROUND More data are needed to define factors that predict long-term success after imiquimod therapy for lentigo maligna (LM). OBJECTIVE We sought to determine the demographic, clinical, and histologic prognostic markers of relapse-free survival in patients with LM who were treated with imiquimod. METHODS This was a single-arm, open-label, nonrandomized, prospective study. RESULTS Eighty-nine patients with histologically confirmed LM and a median follow-up time of 4.8 years after imiquimod treatment were included in our study. Sixteen patients (18%) relapsed. Statistically significant indicators of an increased risk of local recurrence included: the total number of melanocytes, the number of basal and suprabasal melanocytes and the number of pagetoid spreading melanocytes. LIMITATIONS Our study was a single-center, nonrandomized study. CONCLUSION An assessment of different melanocyte fractions in the diagnostic baseline biopsy specimen may help to predict the response of LM to imiquimod therapy.

A follow-up on Acute Pain Services in Germany compared to international survey data.

BACKGROUND After the introduction of instruments for benchmarking, certification and a national guideline for acute pain management, the aim of this study was to describe the current structure, processes and quality of German acute pain services (APS). METHODS All directors of German departments of anaesthesiology were invited to complete a postal questionnaire on structures und processes of acute pain management. The survey asked for staff, techniques and quality criteria, which enabled a comparison to previous data from 1999 and surveys from other countries. RESULTS Four hundred and eight (46%) questionnaires were returned. APS have increased considerably and are now available in 81% of the hospitals, mainly anaesthesia based. However, only 45% fulfilled the minimum quality criteria, such as the assignment of personnel, the organization of patient care during nights and weekends, written protocols for postoperative pain management, regular assessments and documenting pain scores. Staff resources varied considerably, but increased compared to 1999. Two daily rounds were performed in 71%, either by physicians and nurses (42%), by physicians only (25%) or by supervised nurses (31%). Most personnel assigned to the APS shared this work along with other duties. Only 53% of the hospitals had an integrated rotation for training their specialty trainees. CONCLUSIONS The availability of APS in Germany and other countries has increased over the last decade; however, the quality of nearly half of the APS is questionable. Against the disillusioning background of recently reported unfavourable pain-related patient outcomes, the structures, organization and quality of APS should be revisited.

Reversal of cardiomyopathy in propionic acidemia after liver transplantation: a 10-year follow-up

Cardiomyopathy is a frequent complication in propionic acidemia. It is mostly rapidly fatal and independent of the metabolic control or medical intervention. Here, we present the reversal of a severe cardiomyopathy after liver transplantation in a patient with propionic acidemia and the long-term stability after ten years. Liver transplantation in patients with propionic acidemia may be considered a valid and long-lasting treatment when cardiomyopathy is progressive and unresponsive to medical therapy.

Progression of cardiovascular risk factors in black Africans: 3 year follow up of the SABPA cohort study

Recent work identified a high prevalence of modifiable risk factors for cardiovascular disease (CVD) among urban black South Africans. The aim was to track the progression of CVD risk factors in a multi-ethnic sample of South Africans. Participants were 173 black (aged 47.5 ± 7.8 yrs) and 186 white teachers (aged 49.6 ± 9.9 yrs) that were examined at baseline and 3 years follow-up. Blacks demonstrated a substantially higher prevalence of composite CVD burden (defined as history of physician diagnosed heart disease, use of anti-hypertensives, anti-diabetic, or statin medications at either time point) compared to whites (49.1 vs. 32.0%, p = 0.012) respectively. After controlling for baseline, the black participants demonstrated greater increases in 24 h systolic and diastolic blood pressure, total cholesterol, fasting glucose, fibrinogen, D-dimer, and waist circumference in comparison with whites. In summary, an adverse progression of CVD risk factors was observed in the whole sample, although to a larger degree in black participants. Aggressive treatment strategies for controlling risk factors in black Africans are needed to reduce the increasing burden of CVD in South Africa.

Comparison between magnetic resonance imaging and computed tomography of the lung in patients with cystic fibrosis with regard to clinical, laboratory, and pulmonary functional parameters

OBJECTIVE To evaluate whether magnetic resonance imaging (MRI) is effective as computed tomography (CT) in determining morphologic and functional pulmonary changes in patients with cystic fibrosis (CF) in association with multiple clinical parameters. MATERIALS AND METHODS Institutional review board approval and patient written informed consent were obtained. In this prospective study, 30 patients with CF (17 men and 13 women; mean (SD) age, 30.2 (9.2) years; range, 19-52 years) were included. Chest CT was acquired by unenhanced low-dose technique for clinical purposes. Lung MRI (1.5 T) comprised T2- and T1-weighted sequences before and after the application of 0.1-mmol·kg gadobutrol, also considering lung perfusion imaging. All CT and MR images were visually evaluated by using 2 different scoring systems: the modified Helbich and the Eichinger scores. Signal intensity of the peribronchial walls and detected mucus on T2-weighted images as well as signal enhancement of the peribronchial walls on contrast-enhanced T1-weighted sequences were additionally assessed on MRI. For the clinical evaluation, the pulmonary exacerbation rate, laboratory, and pulmonary functional parameters were determined. RESULTS The overall modified Helbich CT score had a mean (SD) of 15.3 (4.8) (range, 3-21) and median of 16.0 (interquartile range [IQR], 6.3). The overall modified Helbich MR score showed slightly, not significantly, lower values (Wilcoxon rank sum test and Student t test; P > 0.05): mean (SD) of 14.3 (4.7) (range, 3-20) and median of 15.0 (IQR, 7.3). Without assessment of perfusion, the overall Eichinger score resulted in the following values for CT vs MR examinations: mean (SD), 20.3 (7.2) (range, 4-31); and median, 21.0 (IQR, 9.5) vs mean (SD), 19.5 (7.1) (range, 4-33); and median, 20.0 (IQR, 9.0). All differences between CT and MR examinations were not significant (Wilcoxon rank sum tests and Student t tests; P > 0.05). In general, the correlations of the CT scores (overall and different imaging parameters) to the clinical parameters were slightly higher compared to the MRI scores. However, if all additional MRI parameters were integrated into the scoring systems, the correlations reached the values of the CT scores. The overall image quality was significantly higher for the CT examinations compared to the MRI sequences. CONCLUSIONS One major diagnostic benefit of lung MRI in CF is the possible acquisition of several different morphologic and functional imaging features without the use of any radiation exposure. Lung MRI shows reliable associations with CT and clinical parameters, which suggests its implementation in CF for routine diagnosis, which would be particularly important in follow-up imaging over the long term.

Whole-exome sequencing reveals a C-terminal germline variant in CEBPA-associated acute myeloid leukemia: 45-year follow-up of a large family.

Familial acute myeloid leukemia is rare and linked to germline mutations in RUNX1, GATA2 or CCAAT/enhancer binding protein-α (CEBPA). We re-evaluated a large family with acute myeloid leukemia originally seen at NIH in 1969. We utilized whole-exome sequencing to study this family, and conducted in silico bioinformatics analysis, protein structural modeling and laboratory experiments to assess the impact of the identified CEBPA Q311P mutation. Unlike most previously identified germline mutations in CEBPA, which were N-terminal frameshift mutations, we identified a novel Q311P variant that was located in the C-terminal bZip domain of C/EBPα. Protein structural modeling suggested that the Q311P mutation alters the ability of the CEBPA dimer to bind DNA. Electrophoretic mobility shift assays showed that the Q311P mutant had attenuated binding to DNA, as predicted by the protein modeling. Consistent with these findings, we found that the Q311P mutation has reduced transactivation, consistent with a loss-of-function mutation. From 45 years of follow-up, we observed incomplete penetrance (46%) of CEBPA Q311P. This study of a large multi-generational pedigree reveals that a germline mutation in the C-terminal bZip domain can alter the ability of C/EBP-α to bind DNA and reduces transactivation, leading to acute myeloid leukemia.

Assessment of the nonoperated root after apical surgery of the other root in mandibular molars: a 5-year follow-up study

INTRODUCTION If a surgical approach is chosen to treat a multirooted tooth affected by persistent periapical pathosis, usually only the affected roots are operated on. The present study assessed the periapical status of the nonoperated root 5 years after apical surgery of the other root in mandibular molars. METHODS Patients treated with apical surgery of mandibular molars with a follow-up of 5 years were selected. Patient-related and clinical parameters (sex, age, smoking, symptoms, and signs of infection) before surgery were recorded. Preoperative intraoral periapical radiographs and radiographs 5 years after surgery were examined. The following data were collected: tooth, operated root, type and quality of the coronal restoration, marginal bone level, length and homogeneity of the root canal filling, presence of a post/screw, periapical index (PAI) of each root, and radiographic healing of the operated root. The presence of apical pathosis of the nonoperated root was analyzed statistically in relation to the recorded variables. RESULTS Thirty-seven patients fulfilled the inclusion criteria. Signs of periapical pathosis in the nonoperated root 5 years after surgery (PAI ≥ 3) could be observed in only 3 cases (8.1%). Therefore, statistical analysis in relation to the variables was not possible. The PAI of the nonoperated root before surgery had a weak correlation with signs of apical pathosis 5 years after surgery. CONCLUSIONS Nonoperated roots rarely developed signs of new apical pathosis 5 years after apical surgery of the other root in mandibular molars. It appears reasonable to resect and fill only roots with a radiographically evident periapical lesion.

Follow-up care of young childhood cancer survivors: attendance and parental involvement.

PURPOSE Despite recommendations, only a proportion of long-term childhood cancer survivors attend follow-up care. We aimed to (1) describe the follow-up attendance of young survivors aged 11-17 years; (2) describe the parental involvement in follow-up, and (3) investigate predictors of follow-up attendance and parental involvement. METHODS As part of the Swiss Childhood Cancer Survivor Study, a follow-up questionnaire was sent to parents of childhood cancer survivors aged 11-17 years. We assessed follow-up attendance of the child, parents' involvement in follow-up, illness perception (Brief IPQ), and sociodemographic data. Clinical data was available from the Swiss Childhood Cancer Registry. RESULTS Of 309 eligible parents, 189 responded (67 %; mean time since diagnosis 11.3 years, range 6.8-17.2) and 75 % (n = 141) reported that their child still attended follow-up. Of these, 83 % (n = 117) reported ≥1 visit per year and 17 % (n = 23) reported <1 visit every year. Most survivors saw pediatric oncologists (n = 111; 79 % of 141), followed by endocrinologists (n = 24, 17 %) and general practitioners (n = 22, 16 %). Most parents (92 %) reported being involved in follow-up (n = 130). In multivariable and Cox regression analyses, longer time since diagnosis (p = 0.025) and lower perceived treatment control (assessed by IPQ4: how much parents thought follow-up can help with late effects; p = 0.009) were associated with non-attendance. Parents' overall information needs was significantly associated with parental involvement in the multivariable model (p = 0.041). CONCLUSION Educating survivors and their parents on the importance and effectiveness of follow-up care might increase attendance in the longer term.

The shorter the better? A follow-up analysis of 10-session psychiatric treatment including the motive-oriented therapeutic relationship for borderline personality disorder

OBJECTIVE: There is little research on short-term treatments for borderline personality disorder (BPD). While the core changes may occur only in long-term treatments, short-term treatments may enable the study of early generic processes of engagement in therapy and thus inform about effective treatment components. It was shown that a 10-session version of a psychiatric treatment was effective in reducing borderline symptoms at the end of this treatment [Kramer, U., Kolly, S., Berthoud, L., Keller, S., Preisig, M., Caspar, F., … Despland, J.-N. (2014). Effects of motive-oriented therapeutic relationship in a ten-session general psychiatric treatment for borderline personality disorder: A randomized controlled trial. Psychotherapy and Psychosomatics, 83, 176-186.]. Also, it was demonstrated in a randomized design that adding the motive-oriented therapeutic relationship (MOTR), following an individualized case formulation based on Plan Analysis, further increased general outcome after session 10 and had a positive effect on the early changes in self-esteem and alliance. METHOD: The present study focuses on the follow-up period after this initial treatment, examining treatment density and outcomes after 6 months and service utilization after 12 months. Outcome was measured using the OQ-45. RESULTS: Results on a sub-sample of N = 40 patients with available OQ-45 data at follow-up (n = 21 for MOTR-treatment, n = 19 for comparison treatment) showed maintenance of gains over the follow-up period, which did not differ between both conditions. It appeared for this sample that MOTR treatments, while using the same number of sessions, lasted more weeks (i.e., lower treatment density, defined as the number of sessions per week), when compared to the treatments without MOTR. Density marginally predicted symptom reduction at follow-up. Patients in MOTR treatments had a greater likelihood of entering structured psychotherapy after the initial sessions than patients in the comparison group. CONCLUSIONS: These results are overall consistent with earlier studies on short-term treatments for BPD and underline the importance of individualizing interventions, by using case formulations that rely on idiographic methods and integrative concepts.

Preferences for the organization of long-term follow-up in adolescent and young adult cancer survivors.

PURPOSE As survival rates of adolescent and young adult (AYA) cancer patients increase, a growing number of AYA cancer survivors need follow-up care. However, there is little research on their preferences for follow-up care. We aimed to (1) describe AYA cancer survivors' preferences for the organization and content of follow-up care, (2) describe their preferences for different models of follow-up, and (3) investigate clinical and sociodemographic characteristics associated with preferences for the different models. METHODS AYA cancer survivors (diagnosed with cancer at age 16-25 years; ≥5 years after diagnosis) were identified through the Cancer Registry Zurich and Zug. Survivors completed a questionnaire on follow-up attendance, preferences for organizational aspects of follow-up care (what is important during follow-up, what should be included during appointments, what specialists should be involved, location), models of follow-up (telephone/questionnaire, general practitioner (GP), pediatric oncologist, medical oncologist, multidisciplinary team), and sociodemographic characteristics. Information on tumor and treatment was available through the Cancer Registry Zurich and Zug. RESULTS Of 389 contacted survivors, 160 (41.1 %) participated and 92 (57.5 %) reported still attending follow-up. Medical aspects of follow-up care were more important than general aspects (p < 0.001). Among different organizational models, follow-up by a medical oncologist was rated higher than all other models (p = 0.002). Non-attenders of follow-up rated GP-led follow-up significantly higher than attenders (p = 0.001). CONCLUSION Swiss AYA cancer survivors valued medical content of follow-up and showed a preference for medical oncologist-led follow-up. Implementation of different models of follow-up care might improve accessibility and attendance among AYA cancer survivors.