Summary Background The standard busulfan–cyclophosphamide myeloablative conditioning regimen is associated with substantial non-relapse mortality in patients older than 40 years with acute myeloid ...leukaemia who are undergoing allogeneic stem-cell transplantation. Because the combination of busulfan plus fludarabine has been proposed to reduce non-relapse mortality, we aimed to compare this treatment with busulfan plus cyclophosphamide as a preparative regimen in these patients. Methods We did an open-label, multicentre, randomised, phase 3 trial for patients with acute myeloid leukaemia at 25 hospital transplant centres in Italy and one in Israel. Eligible patients were aged 40–65 years, had an Eastern Cooperative Oncology Group performance status less than 3, and were in complete remission. Patients were randomly assigned 1:1 to receive intravenous busulfan plus cyclophosphamide or busulfan plus fludarabine. Treatment allocations were not masked to investigators or patients. Randomisation was done centrally via a dedicated web-based system using remote data entry, with patients stratified by donor type and complete remission status. Patients allocated to busulfan plus cyclophosphamide received intravenous busulfan 0·8 mg/kg four times per day during 2 h infusions for four consecutive days (16 doses from days −9 through −6; total dose 12·8 mg/kg) and cyclophosphamide at 60 mg/kg per day for two consecutive days (on days −4 and −3; total dose 120 mg/kg). Patients allocated to busulfan plus fludarabine received the same dose of intravenous busulfan (from days −6 through −3) and fludarabine at 40 mg/m2 per day for four consecutive days (from days −6 through −3; total dose 160 mg/m2 ). The primary endpoint was 1-year non-relapse mortality, which was assessed on an intention-to-treat basis; safety outcomes were assessed in the per-protocol population. This trial has been completed and is registered with ClinicalTrials.gov , number NCT01191957. Findings Between Jan 3, 2008, and Dec 20, 2012, we enrolled and randomly assigned 252 patients to receive busulfan plus cyclophosphamide (n=125) or busulfan plus fludarabine (n=127). Median follow-up was 27·5 months (IQR 9·8–44·3). 1-year non-relapse mortality was 17·2% (95% CI 11·6–25·4) in the busulfan plus cyclophosphamide group and 7·9% (4·3–14·3) in the busulfan plus fludarabine group (Gray's test p=0·026). The most frequently reported grade 3 or higher adverse events were gastrointestinal events (28 23% of 121 patients in the busulfan plus cyclophosphamide group and 26 21% of 124 patients in the busulfan plus fludarabine group) and infections (21 17% patients in the busulfan plus cyclophosphamide group and 13 10% patients in the busulfan plus fludarabine group had at least one such event). Interpretation In older patients with acute myeloid leukaemia, the myeloablative busulfan plus fludarabine conditioning regimen is associated with lower transplant-related mortality than busulfan plus cyclophosphamide, but retains potent antileukaemic activity. Accordingly, this regimen should be regarded as standard of care during the planning of allogeneic transplants for such patients. Funding Agenzia Italiana del Farmaco.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background Whether the use of sevelamer rather than a calcium-containing phosphate binder improves cardiovascular (CV) survival in patients receiving dialysis remains to be elucidated. Study Design ...Open-label randomized controlled trial with parallel groups. Settings & Participants 466 incident hemodialysis patients recruited from 18 centers in Italy. Intervention Study participants were randomly assigned in a 1:1 fashion to receive either sevelamer or a calcium-containing phosphate binder (although not required by the protocol, all patients in this group received calcium carbonate) for 24 months. Outcomes All individuals were followed up until completion of 36 months of follow-up or censoring. CV death due to cardiac arrhythmias was regarded as the primary end point. Measurements Blind event adjudication. Results At baseline, patients allocated to sevelamer had higher serum phosphorus (mean, 5.6 ± 1.7 SD vs 4.8 ± 1.4 mg/dL) and C-reactive protein levels (mean, 8.8 ± 13.4 vs 5.9 ± 6.8 mg/dL) and lower coronary artery calcification scores (median, 19 IQR, 0-30 vs 30 IQR, 7-180). At study completion, serum phosphate levels were lower in the sevelamer arm (median dosages, 4,800 and 2,000 mg/d for sevelamer and calcium carbonate, respectively). After a mean follow-up of 28 ± 10 months, 128 deaths were recorded (29 and 88 due to cardiac arrhythmias and all-cause CV death). Sevelamer-treated patients experienced lower CV mortality due to cardiac arrhythmias compared with patients treated with calcium carbonate (HR, 0.06; 95% CI, 0.01-0.25; P < 0.001). Similar results were noted for all-cause CV mortality and all-cause mortality, but not for non-CV mortality. Adjustments for potential confounders did not affect results. Limitations Open-label design, higher baseline coronary artery calcification burden in calcium carbonate–treated patients, different mineral metabolism control in sevelamer-treated patients, overall lower than expected mortality. Conclusions These results show that sevelamer compared to a calcium-containing phosphate binder improves survival in a cohort of incident hemodialysis patients. However, the better outcomes in the sevelamer group may be due to better phosphate control rather than reduction in calcium load.
This prospective multicenter randomized study aimed to compare the efficacy of 3 common ablation methods used for longstanding permanent atrial fibrillation (AF).
A total of 144 patients with ...longstanding permanent AF (median duration 28 months) were randomly assigned to circumferential pulmonary vein ablation (CPVA, group 1, n = 47), to pulmonary vein antrum isolation (PVAI, group 2, n = 48) or to a hybrid strategy combining ablation of complex fractionated or rapid atrial electrograms (CFAE) in both atria followed by a pulmonary vein antrum isolation (CFAE + PVAI, group 3, n = 49).
Scarring in the left atrium and structural heart disease/hypertension were present in most patients (65%). After a mean follow-up of 16 months, 11% of patients in group 1, 40% of patients in group 2 and 61% of patients in group 3 were in sinus rhythm after one procedure and with no antiarrhythmic drugs (P < .001). Sinus rhythm maintenance would increase respectively to 28% (group 1), 83% (group 2), and 94% (group 3) after 2 procedures and with antiarrhythmic drugs (AADs, P < .001). The AF terminated during ablation, either by conversion to sinus rhythm or organization into an atrial tachyarrhythmia, in 13% of patients (group 1), 44% (group 2), and 74% (group 3) respectively. CFAE alone, performed as the first step of the ablation in group 3, organized AF in only 1 patient.
In this study, the hybrid AF ablation strategy including antrum isolation and CFAE ablation had the highest likelihood of maintaining sinus rhythm in patients with longstanding permanent AF. Electrical isolation of the PVs, although inadequate if performed alone, is relevant to achieve long-term sinus rhythm maintenance after ablation. Bi-atrial CFAE ablation had a minimal impact on AF termination during ablation.
Objective The purpose of this prospective study was: 1) to follow-up a large number of endodontic treatments performed by a single operator, periodically checked over a 5-year period; and 2) to ...correlate outcome to a number of clinical variables. Study design This prospective study included all consecutive cases during the selected time period. All cases were followed regularly for a 5-year period. At the 5-year end point of the study, 470 patients with 816 treated teeth and with 1,369 treated root canals were available for evaluation. Results The overall rate of success among the 816 teeth/1,369 root canals available for evaluation was 88.6%/90.3%. The success rate for 435 teeth/793 root canals undergoing vital pulp therapy was 91.5%/93.1%. Teeth/root canals with necrotic pulp but without detectable periapical bone lesion were successfully treated in 89.5%/92.3%. If the pulp necrosis was complicated by apical periodontitis, the success rate fell to 82.7% for the teeth and 84.1% for the root canals ( P = .037). Teeth with periapical lesion <5 mm had a success rate of 86.6%, and in cases where the lesion was ≥5 mm the rate of success was 78.2%. Conclusions More severe disease conditions negatively affects outcome. An optimal working length was identified. Excess of root canal filling material decreases success. Infected pulp space should be treated with an effective intracanal dressing. The quality of the coronal restoration or the placement of intracanal post retentions does not affect treatment outcome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract The immunocompromised cutaneous district (ICD) is a novel pathogenic concept that refers to the occurrence of opportunistic skin disorders (such as infections, malignancies, and immune ...diseases) at a cutaneous site previously marked by a damaging event, usually involving the local lymph network or peripheral sensory nerves. In addition to herpetic infections, which are notoriously harmful for sensory nerve fibers and therefore already included among the potential causes of ICD, there are a large and variegate group of further neurologic diseases, both peripheral (carpal tunnel syndrome, facial nerve palsy, and trigeminal trophic syndrome) and central (poliomyelitis and brain stroke), which may be added to the wide and expanding spectrum of injuring events resulting in an ICD. The neural compartment of skin immunity plays a key role in immune homeostasis, and this assertion is confirmed by the fact that any neurologic injury, whatever the origin (peripheral or central) or the cause (infection, trauma, ischemia), can give rise to immune destabilization of the innervated area, which becomes a site prone to the occurrence of opportunistic skin disorders. A neural-driven process may be responsible for the cutaneous immune dysregulation ensuing from some neurologic diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Introduction The management of ruptured intracranial false aneurysms (IFAs) might be tricky as any kind of treatment modality, surgical or endovascular, is burdened with significant ...challenges. A case report of the endovascular treatment of IFA in emergency setting is presented to provide more understanding of its pathophysiology as well as of the best operative work-up for petrous carotid artery reconstruction. Methods Technical notes from a left sided skull base abscess, involving and eroding the carotid canal and petrous carotid artery (PCA) resulting in an IFA are shown and analyzed. Results Balloon-assisted low viscosity Onyx embolization seems an effective method for the emergency treatment of IFA. Indications, technical nuances, and peri- and post-procedural complications are thoroughly discussed. A flow chart for the management of IFA is also proposed. Conclusions The combination of parent artery balloon protection and low viscosity Onyx embolization can provide an effective occlusion of the IFA while maintaining parent artery patency. Normal distal filling of the parent artery, and optimal obliteration of the IFA are easily achievable.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Category:
Ankle; Sports
Introduction/Purpose:
Multiple Level I meta-analyses have been led comparing traditional static vs. more recently-introduced dynamic strategies of fixation for injuries of the ...distal tibiofibular syndesmosis (TFS). The aim of this review was to assess their robustness and methodological quality, providing support in the choice of a treatment strategy in case of TFS injury using the highest level of evidence.
Methods:
In this systematic review, conducted in accordance with the PRISMA guidelines, we identified meta-analyses/systematic reviews comparing static and dynamic fixation methods after acute TFS injury. Robustness of studies was evaluated using the Fragility Index (FI) for meta-analysis and the Fragility Quotient (FQ). The risk of bias was evaluated using the Assessment of Multiple Systematic Reviews(AMSTAR) instrument. Finally, the Jadad Decision Algorithm was applied to select the study which provided the highest quality of evidence to develop recommendations for the fixation strategy of these lesions.
Results:
Out of 1302 records, 4 Level I meta-analyses were included in this study. Analyzing the statistically significant dichotomous outcomes, the median FI was 3.5 (IQR, 2 to 5.5; range, 1 to 9) while the median FQ was 1.9% (IQR, 1 to 3.5; range 0.35 to 4.4). In total, 37% had a FI of 2 or less and 75% of outcomes had a FI of 4 or less. According to the AMSTAR score and Jadad algorithm, the largest meta-analysis was selected as the highest evidence provided so far.
Conclusion:
We selected the meta-analysis by Grassi et al. as the highest quality provided so far, which found that dynamic fixation reduced complication rates and improved clinical outcomes compared to static methods of fixation. We demonstrated that meta-analyses with statistically significant dichotomous outcomes comparing dynamic and static fixation for treating injuries of the distal tibiofibular syndesmosis are fragile, with a change in less than 4 patients or less than 2% of the study population sufficient to reverse a significant outcome to nonsignificant. Based on these findings, we recommend caution when interpreting the results of these studies.
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