Whereas distal cholangiocarcinoma (DC) is treated by pancreatoduodenectomy (PD), consensus is lacking on treatment of mid-bile duct carcinoma (mid-BDC) without involvement of the pancreatic head. ...Both PD or a local resection (LR) of the extrahepatic bile duct with lymphadenectomy are being used. The aim of this study was to compare outcomes after PD and LR for mid-BDC and, for reference, PD for DC.
Retrospective monocenter study including consecutive patients who underwent LR for mid-BDC (LR), PD for mid-BDC (PD-mid) and PD for DC (PD-distal) between 2000 and 2016. Clinicopathologic characteristics, postoperative outcomes and survival were compared.
A total of 184 patients were included (LR, 22; PD-mid, 38; PD-distal, 124). Postoperative mortality was 0% following LR, 5% (2/22) for PD-mid and 3% (4/124) for PD-distal, p = 0.542. Major complications occurred in 5/22 patients (23%), 19/39 (50%) and 46/124 (37%) respectively, p = 0.103 (LR versus PD-mid, p = 0.038).
Tumor size, differentiation grade and resection margin status were comparable across groups. Median number of resected lymph nodes was 5 (range 3–7), 9 (7–14) and 12 (8–16) respectively, p < 0.001. Median overall survival was 46 months (95%CI 10–82), 19 months. (95%CI 11–27), and 29 months (95%CI 23–35) respectively, p = 0.39 (LR versus PD-mid, p = 0.20). Disease-free survival also did not differ.
LR is an acceptable treatment for selected patients with mid-BDC, showing less morbidity and comparable survival despite smaller lymph node retrieval.
In patients with mild to moderate symptomatic carotid artery stenosis, intraplaque hemorrhage (IPH) and a thin/ruptured fibrous cap (FC) as evaluated with MRI, and the presence of microembolic ...signals (MESs) as detected with transcranial Doppler, are associated with an increased risk of a (recurrent) stroke. The objective of the present study is to determine whether the prevalence of MES differs in patients with and without IPH and thin/ruptured FC, and patients with only a thin/ruptured FC without IPH.
In this multicenter, diagnostic cohort study, patients with recent transient ischemic attack or minor stroke in the carotid territory and an ipsilateral mild to moderate carotid artery plaque were included. IPH and FC status were dichotomously scored. Analysis of transcranial Doppler data was done blinded for the MRI results. Differences between groups were analyzed with Fisher exact test.
A total of 113 patients were included. Transcranial Doppler measurements were feasible in 105 patients (average recording time, 219 minutes). A total of 26 MESs were detected in 8 of 105 patients. In 44 of 105 plaques IPH was present. In 92 of 105 plaques FC status was assessable, 36 of these had a thin/ruptured FC. No significant difference in the prevalence of MES between patients with and without IPH (P=0.46) or with thick versus thin/ruptured FC (P=0.48) was found.
In patients with a symptomatic mild to moderate carotid artery stenosis, IPH and FC status are not associated with MES. This suggests that MRI and transcranial Doppler provide different information on plaque vulnerability.
http://www.clinicaltrials.gov. Unique identifier: NCT01709045.
Longevity may depend on a balance between tumor suppression and tissue renewal mechanisms Campisi, J., 2003. Cancer and ageing: rival demons? Nat. Rev. Cancer 3 (5), 339-349. Mice with constitutively ...activated p53 are almost cancer free but their life span is reduced and accompanied by early tissue atrophy Tyner et al., 2002. p53 mutant mice that display early ageing-associated phenotypes. Nature 415 (6867) 45-53. Replacement of arginine (Arg) by proline (Pro) at position 72 of human p53 decreases its apoptotic potential Dumont et al., 2003. The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat. Genet. 33 (3), 357-365 providing a tool to test for a similar trade-off in humans. Using a formal meta-analysis of the published literature we show that carriers of the TP53 codon 72 Pro/Pro genotype have an increased cancer risk compared to Arg/Arg carriers (p<0.05). Next, in a prospective study of 1226 people aged 85 years and over we show that carriers of the Pro/Pro genotype have a 41% increased survival (p = 0.032) despite a 2.54 fold increased (p = 0.007) proportional mortality from cancer. It is suggested that human p53 protect against cancer but at a cost of longevity.
Carotid plaque composition is a major determinant of cerebrovascular events. In the present analysis, we evaluated the relationship between intraplaque hemorrhage (IPH) and a thin/ruptured fibrous ...cap (TRFC) in moderately stenosed carotid arteries and cerebral infarcts on MRI in the ipsilateral hemisphere.
A total of 101 patients with a symptomatic 30% to 69% carotid artery stenosis underwent MRI of the carotid arteries and the brain, within a median time of 45 days from onset of symptoms. The presence of ipsilateral infarcts in patients with and without IPH and TRFC was evaluated.
IPH was seen in 40 of 101 plaques. TRFC was seen in 49 of 86 plaques (postcontrast series were not obtained in 15 patients). In total, 51 infarcts in the flow territory of the symptomatic carotid artery were found in 47 patients. Twenty nine of these infarcts, found in 24 patients, were cortical infarcts. No significant relationship was found between IPH or TRFC and the presence of ipsilateral infarcts.
MRI detected IPH and TRFC are not related to the presence of old and recent cortical and subcortical infarcts ipsilateral to a symptomatic carotid artery stenosis of 30% to 69%.
http://www.clinicaltrials.gov. Unique identifier: NCT01208025.
Background
In 1998, a survey of the European Society for Paediatric Nephrology (ESPN) revealed substantial disparities in pediatric renal care among European countries. Therefore, ESPN aimed at ...harmonizing renal care in all European countries in the following 20 years. In 2017, we conducted a survey to evaluate the current status of renal health policies for children in Europe.
Methods
A 33-question web-based survey was designed and sent to presidents or representatives of national societies of pediatric nephrology in 44 European countries.
Results
Data was reported from 42 (95.5%) countries. The number of pediatric nephrologists per million child population increased from 1998 to 2017 in 70% of countries. Pediatric dialysis facilities for acute kidney injury and end-stage kidney disease were available in 95% of countries. The availability of pediatric kidney transplantation increased from 55 to 93% of countries. Considerable variation was found in the current availability of allied health professionals, including psychosocial and nutritional support, high-tech diagnostic methods, and treatment with expensive drugs for children with kidney diseases between different European countries.
Conclusions
The 20-year follow-up analysis of pediatric renal care services in European countries revealed that pediatric nephrology has become a well-established subspecialty in pediatrics and nephrology in 2017. The ESPN will continue its efforts to further improve pediatric renal care for European children by harmonizing remaining disparities of renal care services.
Optimal blood pressure (BP) targets before endovascular treatment (EVT) for acute ischemic stroke are unknown. We aimed to assess the relation between admission BP and clinical outcomes and ...successful reperfusion after EVT.
We used data from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, an observational, prospective, nationwide cohort study of patients with ischemic stroke treated with EVT in routine clinical practice in the Netherlands. Baseline systolic BP (SBP) and diastolic BP (DBP) were recorded on admission. The primary outcome was the score on the modified Rankin Scale at 90 days. Secondary outcomes included successful reperfusion (extended Thrombolysis in Cerebral Infarction score 2B-3), symptomatic intracranial hemorrhage, and 90-day mortality. Multivariable logistic and linear regression were used to assess the associations of SBP and DBP with outcomes. The relations between BPs and outcomes were tested for nonlinearity. Parameter estimates were calculated per 10 mm Hg increase or decrease in BP.
We included 3180 patients treated with EVT between March 2014 and November 2017. The relations between admission SBP and DBP with 90-day modified Rankin Scale scores and mortality were J-shaped, with inflection points around 150 and 81 mm Hg, respectively. An increase in SBP above 150 mm Hg was associated with poor functional outcome (adjusted common odds ratio, 1.09 95% CI, 1.04-1.15) and mortality at 90 days (adjusted odds ratio, 1.09 95% CI, 1.03-1.16). Following linear relationships, higher SBP was associated with a lower probability of successful reperfusion (adjusted odds ratio, 0.97 95% CI, 0.94-0.99) and with the occurrence of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.06 95% CI, 0.99-1.13). Results for DBP were largely similar.
In patients with acute ischemic stroke treated with EVT, higher admission BP is associated with lower probability of successful reperfusion and with poor clinical outcomes. Further research is needed to investigate whether these patients benefit from BP reduction before EVT.
MPA is an immunosuppressive agent used to prevent graft rejection after renal transplantation. MPA shows considerable inter‐ and intraindividual variability in exposure in children and has a defined ...therapeutic window, and TDM is applied to individualize therapy. We aimed to study the exposure to MPA measured as the AUC in pediatric renal transplant patients, to identify factors influencing exposure and to assess target attainment. Children transplanted between 1998 and 2014 in a single center were included. Two groups were identified: Group 1 (AUC <3 wk post‐transplantation) and Group 2 (AUC >18 months post‐transplantation). Therapeutic targets were set at: AUC0–12h of 30–60 mg h/L. A total of 39 children were included in Group 1 (median age 13.3 yr) vs. 14 in Group 2 (median age 13.4 yr). AUC0–12h was 29.7 mg h/L in Group 1 and 56.6 mg h/L in Group 2, despite a lower dosage in Group 2 (584 and 426 mg/m2, respectively). About 46% of patients reached the target AUC0–12h in Group 1. Time since transplantation and serum creatinine were significantly associated with MPA exposure (p < 0.001), explaining 36% of the variability. Individualization of the mycophenolate dose by more intense and more early TDM could improve target attainment.
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