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The purpose of this article is to summarize challenges and make recommendations regarding the integration of counter-small unmanned aerial systems (C-SUAS) at the infantry brigade combat team (IBCT) and below [...]

Concentrations of chain-breaking antioxidants were studied in the first 6 postnatal weeks in 29 healthy preterm infants (gestational age 30-35 wk). Vitamin C, uric acid, and sulfhydryl groups declined, whereas vitamin E rose and bilirubin followed its typical biphasic postnatal course. The influence of these changes on the plasma peroxyl radical trapping capacity was assessed in vitro (TRAP assay). The trapping capacity decreased postnatally and this appeared to be related to the coincident fall in uric acid concentrations. Results did not differ between babies fed with only preterm formula (n = 12) and those fed predominantly with human milk (n = 6), except for higher bilirubin and TRAP values in the breast-fed infants. There are major postnatal changes in the concentrations of the plasma chain-breaking antioxidants and this may influence the susceptibility of the preterm baby to oxygen toxicity.

This retrospective study evaluates our strategy to limit prosthetic reconstructions for aortoiliac obstructive disease to the diseased segments in 518 patients. There were 363 (70%) reconstructions without femoral anastomotic sites (FEM-0), 107 (21%) reconstructions with one femoral anastomotic site (FEM-1), and 48 (9%) aortobifemoral reconstructions (FEM-2). The ischemic symptoms and the extent of obstructions were significantly more severe in the FEM-1 and FEM-2 groups than in the FEM-0 group. Early operative results were comparable in all three groups. The difference in outcome became apparent when the long-term results were considered. Long-term follow-up continued for up to 20 years after the operation. Primary and secondary patency rates were significantly higher in the FEM-0 group (9% and 4% recurrent obstructions per 5 years, respectively) than in the FEM-1 and FEM-2 groups (both 14% and 10%, respectively), which was explained by patient selection. Late additional surgery was performed after aortoiliac procedures in most cases for recurrent aortoiliac obstruction and after aortofemoral procedures in most cases for false aneurysms. The risk of late additional operations during long-term follow-up were significantly lower in the FEM-0 group than in the FEM-1 and FEM-2 groups. These results support our strategy to tailor prosthetic reconstructive surgery to the individual status of the aortoiliac arteries.

International dispute resolution continues to evolve under GATT, with the rules of competition becoming more solidified, as the number of disputes and the methods for resolving them grows. The advent of established rules will facilitate such resolution by making it more automatic and legislative. However, consultation and negotiation between the two disputing parties will continue to be encouraged. Resolution of the dispute between the US and the EC over the EC's subsidization of the oilseed industry illustrates the constructive nature of such a process.

Studies of popliteal aneurysms, localized thinning of the wall of the artery in the knee area, indicate that clot formation is a frequent complication, which is often associated with amputation. Early diagnosis of these aneurysms and reconstructive surgery have been shown to prevent these complications. Although it has been observed that multiple aneurysms may be present at the time the popliteal aneurysm is identified, there is no information available concerning the risk for developing new aneurysms. A study was undertaken of 50 patients treated for 71 popliteal aneurysms to determine the long-term results of surgical and nonsurgical treatment, and to determine if these patients were at increased risk for developing new aneurysms. Follow-up ranged from 1 month to 23 years; average follow-up was five years. Initial treatment was nonsurgical for 25 aneurysms (35 percent) and surgical for 46 (65 percent). Of the 25 initially treated nonsurgically, 21 were without symptoms, and 12 of these developed complications (57 percent); two of the four symptomatic aneurysms lead to complications. There was a 74 percent probability of developing complications within five years. For those who received surgical treatment, 10-year follow-up revealed a 64 percent graft patency; amputation was avoided in 95 percent. Sixteen patients (32 percent) developed arteriosclerotic aneurysms at other locations. Ten years after surgery, the probability of developing a new aneurysm was 49 percent. Overall, the most significant risk factor was multiple, isolated aneurysms at the time of initial diagnosis; these patients had the highest mortality. These results confirm the potential of untreated popliteal aneurysm to result in loss of limb, as well as being associated with an increased risk for new aneurysm formation. Patients with popliteal artery aneurysm should undergo preventative surgery and be followed closely. (Consumer Summary produced by Reliance Medical Information, Inc.)

Premature infants may undergo developmental assessment so that those with developmental delays or impairments in vision, hearing, or other areas might be identified and treated early. These infants may benefit from stimulation programs. However, there is no generally accepted approach for assessing these infants to take into account their preterm status. Correction for the full extent, half, or none of the prematurity has been advocated for different purposes. Early identification might be aided by using chronological age without correction, while parental anxiety and over-referral of infants to stimulation programs may be avoided if full correction is used. Another consideration is that full compensation for prematurity sometimes leads to overcorrection. To better determine how correction for premature birth should be applied, the developmental milestones of 555 non-handicapped premature infants were compared with those of 550 non-handicapped full-term infants. When corrected age was used, 80 to 99 percent of premature children achieved appropriate milestones, while only 30 to 80 percent did so when chronologic age was used. However, over 90 percent scored appropriately, regardless of correction, when tested at two years of age. The distribution of children's performance was more varied in premature than in term children, which may reflect the effect of prematurity or of environmental stimulation. The results suggest that correction for prematurity during developmental assessment is appropriate during the first but not the second year of life. A longer-term study is needed to determine whether this conclusion can be applied to language problems that are detectable only at later ages. (Consumer Summary produced by Reliance Medical Information, Inc.)

Background: Compliance rates with patient-reported outcome measures (PROMs) collected alongside arthroplasty registries vary in the literature. We described the feasibility of a routinely collected set PROMs alongside the Dutch Arthroplasty Register.Methods: The longitudinal Leiden Orthopaedics Outcomes of OsteoArthritis Study is a multicenter (7 hospitals), observational study including patients undergoing total hip or total knee arthroplasty (THA or TKA). A set of PROMs: Short Form-12, EuroQol 5 Dimensions, Hip/Knee injury and Osteoarthritis Outcome Score, Oxford Hip/Knee Score was collected preoperatively and at 6, 12, 24 months, and every 2 years thereafter. Participation rates and response rates were recorded.Results: Between June 2012 and December 2014, 1796 THA and 1636 TKA patients were invited, of whom 1043 THA (58%; mean age 68 years [standard deviation, SD: 10]) and 970 TKA patients (59%; mean age 71 years [SD 9.5]) participated in the study. At 6 months, 35 THA/38 TKA patients were lost to follow-up. Response rates were 90% for THA (898/1000) and 89% for TKA (827/932) participants. At 1 and 2 years, 8 and 18 THA and 17 and 11 TKA patients were lost to follow-up, respectively. The response rates among those eligible were 87% (866/992) and 84% (812/972) for THA and 84% (771/917) and 83% (756/906) for TKA patients, respectively. The 2-year questionnaire was completed by 78.5% of the included THA patients and by 77.9% of the included TKA patients.Conclusions: About 60% of patients undergoing THA or TKA complete PROMs preoperatively, with more than 80% returning follow-up PROMs. To increase the participation rates, more efforts concerning the initial recruitment of patients are needed.

In many healthcare settings, benchmarking for complex procedures has become a mandatory requirement by competent authorities, regulators, payers and patients to assure clinical performance, cost-effectiveness and safe care of patients. In several countries inside and outside Europe, benchmarking systems have been established for haematopoietic stem cell transplantation (HSCT), but access is not universal. As benchmarking is now integrated into the FACT-JACIE standards, the EBMT and JACIE established a Clinical Outcomes Group (COG) to develop and introduce a universal system accessible across EBMT members. Established systems from seven European countries (United Kingdom, Italy, Belgium, France, Germany, Spain, Switzerland), USA and Australia were appraised, revealing similarities in process, but wide variations in selection criteria and statistical methods. In tandem, the COG developed the first phase of a bespoke risk-adapted international benchmarking model for one-year survival following allogeneic and autologous HSCT based on current capabilities within the EBMT registry core dataset. Data completeness, which has a critical impact on validity of centre comparisons, is also assessed. Ongoing development will include further scientific validation of the model, incorporation of further variables (when appropriate) alongside implementation of systems for clinically meaningful interpretation and governance aiming to maximise acceptance to centres, clinicians, payers and patients across EBMT.

In June, 2017, the Wuhan Intermediate People's Court became the first Chinese court to recognize a U.S. judgment in the case of Liu Li v. Tao Li & Tong Wu. The Liu case is a significant development in Chinese private international law, but represents more than a single decision in a single case. It is one piece of a developing puzzle in which the law on the recognition and enforcement of foreign judgments in China is a part of a larger set of developments. These developments are inextricably tied to the "One Belt and One Road," or "Belt and Road" Initiative first announced by Chinese President Xi Jinping on a visit to Kazakhstan in 2013. This article traces the development of the Liu case, from the first judgment in California to the decision to recognize and enforce that judgment in Wuhan, China. It then provides the context within which the decision on recognition and enforcement was made, and the way the decision fits within President Xi's "Belt and Road" Initiative and the pronouncements of the Chinese People's Supreme Court which have encouraged the recognition and enforcement of foreign judgments as part of that Initiative. [ABSTRACT FROM AUTHOR]

Background Percutaneous laser disc decompression (PLDD) for patients with lumbar disc herniation is believed to be cheaper than surgery. However, cost-effectiveness has never been studied.Materials and Methods A cost utility analysis was performed alongside a randomized controlled trial comparing PLDD and conventional surgery. Patients reported their quality of life using the EuroQol five dimensions questionnaire (EQ-5D), 36-item short form health survey (SF-36 and derived SF-6D) and a visual analogue scale (VAS). Using cost diaries patients reported health care use, non-health care use and hours of absenteeism from work. The 1-year societal costs were compared with 1-year quality adjusted life years (QALYs) based on the United States (US) EQ-5D. Sensitivity analyses were carried out on the use of different utility measures (Netherland (NL) EQ-5D, SF-6D, or VAS) and on the perspective (societal or healthcare).Results On the US EQ-5D, conventional surgery provided a non-significant gain in QALYs of 0.033 (95% confidence interval (CI) −0.026 to 0.093) in the first year. PLDD resulted in significantly lower healthcare costs (difference €1771, 95% CI €303 to €3238) and non-significantly lower societal costs (difference €2379, 95% CI −€2860 to €7618). For low values of the willingness to pay for a QALY, the probability of being cost-effective is in favor of PLDD. For higher values of the willingness to pay, between €30,000 and €70,000, conventional microdiscectomy becomes favorable.Conclusions From a healthcare perspective PLDD, followed by surgery when needed, results in significantly lower 1-year costs than conventional surgery. From a societal perspective PLDD appears to be an economically neutral innovation.

Background Percutaneous laser disc decompression is a minimally invasive treatment, for lumbar disc herniation and might serve as an alternative to surgical management of sciatica. In a randomised trial with two-year follow-up we assessed the clinical effectiveness of percutaneous laser disc decompression compared to conventional surgery.Materials and methods This multicentre randomised prospective trial with a non-inferiority design, was carried out according to an intent-to-treat protocol with full institutional review board approval. One hundred and fifteen eligible surgical candidates, with sciatica from a disc herniation smaller than one-third of the spinal canal, were randomly allocated to percutaneous laser disc decompression (n= 55) or conventional surgery (n= 57). The main outcome measures for this trial were the Roland-Morris Disability Questionnaire for sciatica, visual analogue scores for back and leg pain and the patient's report of perceived recovery.Results The primary outcome measures showed no significant difference or clinically relevant difference between the two groups at two-year follow-up. The re-operation rate was 21% in the surgery group, which is relatively high, and with an even higher 52% in the percutaneous laser disc decompression group.Conclusion At two-year follow-up, a strategy of percutaneous laser disc decompression, followed by surgery if needed, resulted in non-inferior outcomes compared to a strategy of microdiscectomy. Although the rate of reoperation in the percutaneous laser disc decompression group was higher than expected, surgery could be avoided in 48% of those patients that were originally candidates for surgery. Percutaneous laser disc decompression, as a non-surgical method, could have a place in the treatment arsenal of sciatica caused by contained herniated discs.

BackgroundThe reference surgical procedure for the treatment of lumbar disc herniation is open microdiscectomy. Minimal invasive discectomy with tubular retractors is hypothesised to cause less tissue damage and result in lower blood loss, less postoperative pain and faster recovery. We previously reported our 1 and 2-year results, and found no better outcomes of tubular discectomy compared with open microdiscectomy. Until now, no studies on tubular discectomy have reported results with more than 2 years of follow-up. Studies with long-term follow-up are required to determine if clinical outcomes are sustained and to assess specific long-term outcomes such as reoperation rate and iatrogenic low back pain due to impaired spinal integrity. The aim of this study is to evaluate the 5-year results of tubular discectomy compared with conventional microdiscectomy.MethodsThe study was designed as a double-blind randomised controlled trial. 325 patients with a symptomatic lumbar disc herniation were randomly allocated to tubular discectomy (166 patients) or conventional microdiscectomy (159 patients). Repeated standardised follow-up measurements were performed at 2, 4, 6, 8, 12, 26, 38, 52, 78, 104, 156, 208 and 260 weeks after randomisation. Main outcomes are the Roland-Morris Disability Questionnaire for Sciatica (RDQ), Visual Analogue Scale for leg pain and low back pain, self-perceived recovery and reoperation incidence.ResultsThere was no clinically significant difference between tubular discectomy and conventional microdiscectomy regarding the main clinical outcomes at any time point during the 5 years of follow-up. RDQ scores at 5 years were 4.3 (95% CI 3.3 to 5.2) in the tubular discectomy group and 3.4 (95% CI 2.4 to 4.5) in the conventional microdiscectomy group. The mean difference of 0.9 (95% CI −0.6 to 2.2) was not significant. Mean differences for leg pain and back pain were 0.2 (95% CI −5.5 to 6.0) and 0.4 (95% CI −5.9 to 6.7), respectively. 77% of patients allocated to conventional discectomy reported complete or near-complete recovery of symptoms compared with 74% of patients allocated to tubular discectomy (p=0.79). The reoperation rate was 18% in the tubular discectomy group and 13% in the conventional discectomy group (p=0.29).ConclusionsLong-term functional and clinical outcome did not differ between patients allocated to tubular discectomy and conventional microdiscectomy. Primary and secondary outcome measures did not support the hypothesised advantages of tubular discectomy over conventional microdiscectomy.Trial registration numberISRCTN51857546.

Limb length discrepancy (LLD) and other patient factors are thought to influence the complication rate in (paediatric) limb deformity correction. In the literature, information is conflicting. This study was performed to identify clinical factors that affect the complication rate in paediatric lower-limb lengthening. A consecutive group of 37 children was analysed. The median proportionate LLD was 15 (4–42). An analysis was carried out on several patient factors that may complicate the treatment or end result using logistic regression in a polytomous logistic regression model. The factors analysed were proportionate LLD, cause of deformity, location of corrected bone, and the classification of the deformity according to an overall classification that includes the LLD and all concomitant deformity factors. The median age at the start of the treatment was 11 (6–17) years. The median lengthening index was 1.5 (0.8–3.8) months per centimetre lengthening. The obstacle and complication rate was 69 per lengthened bone. Proportionate LLD was the only statistically significant predictor for the occurrence of complications. Concomitant deformities did not influence the complication rate. From these data we constructed a simple graph that shows the relationship between proportionate LLD and risk for complications. This study shows that only relative LLD is a predictor of the risk for complications. The additional value of this analysis is the production of a simple graph. Construction of this graph using data of a patient group (for example, your own) may allow a more realistic comparison with results in the literature than has been possible before.

We present results of a phase 3 randomized trial of autografting in chronic lymphocytic leukemia versus observation for responding patients after first- or second-line treatment. The primary objective was to demonstrate that autografting improves the 5-year event-free survival (EFS) from 30% to 50%. There were 223 enrolled patients, 72% men and 28% women, 83% after first and 17% after second-line treatment. Binet stages were progressive A 13%, B 67%, C 20%; at randomization, 59% were in complete remission, and 41% in less than complete remission. Patients were randomized between autografting (n = 112) and observation (n = 111). Median EFS was 24.4 months (range, 16.7-32 months) in the observation group and 51.2 months (39.8-62.5 months) in the autografting group; the 5-year EFS was 24% and 42%, respectively (P < .001). Accordingly, the 5-year relapse incidence was 76% versus 54% (P < .001). Median time to relapse requiring therapy or death was 40 months (25-56 months) in the observation arm and 65 months (59-71 months) after autografting (P = .002). Cox modeling confirmed that autografting significantly improved EFS (hazard ratio 0.44, 95% confidence interval 0.30-0.65; P < .001). At 5 years, the probability of OS was 85.5% and 84.3% for autografting and observation, respectively (P = .77). In chronic lymphocytic leukemia, consolidating autografting reduces the risk of progression by more than 50% but has no effect on overall survival.

The author discusses the lessons learned from the efforts of U.S. legal education in bringing change in transition countries. He looks to law schools around the globe, especially in transition countries, for examples of what should be considered before U.S. law schools engage in such change. He highlights the need to evaluate what are being done in U.S. law schools by the impact they have on the rest of the world and by the impact they have on their graduates who will practice law in the U.S. The standards to be achieved should be how far U.S. legal education takes the world.

From 2002 to 2007, 103 patients with primary myelofibrosis or postessential thrombocythemia and polycythemia vera myelofibrosis and a median age of 55 years (range, 32-68 years) were included in a prospective multicenter phase 2 trial to determine efficacy of a busulfan (10 mg/kg)/fludarabine (180 mg/m2)–based reduced-intensity conditioning regimen followed by allogeneic stem cell transplantation from related (n = 33) or unrelated donors (n = 70). All but 2 patients (2%) showed leukocyte and platelet engraftment after a median of 18 and 22 days, respectively. Acute graft-versus-host disease grade 2 to 4 occurred in 27% and chronic graft-versus-host disease in 43% of the patients. Cumulative incidence of nonrelapse mortality at 1 year was 16% (95% confidence interval, 9%-23%) and significantly lower for patients with a completely matched donor (12% vs 38%; P = .003). The cumulative incidence of relapse at 3 years was 22% (95% confidence interval, 13%-31%) and was influenced by Lille risk profile (low, 14%; intermediate, 22%; and high, 34%; P = .02). The estimated 5-year event-free and overall survival was 51% and 67%, respectively. In a multivariate analysis, age older than 55 years (hazard ratio = 2.70; P = .02) and human leukocyte antigen–mismatched donor (hazard ratio = 3.04; P = .006) remained significant factors for survival. The study was registered at www.clinicaltrials.gov as #NCT 00599547.

OBJECTIVE: To determine whether the faster recovery after early surgery for sciatica compared with prolonged conservative care is attained at reasonable costs. Design Cost utility analysis alongside a randomised controlled trial. Setting Nine Dutch hospitals. Participants 283 patients with sciatica for 6-12 weeks, caused by lumbar disc herniation. Interventions Six months of prolonged conservative care compared with early surgery. MAIN OUTCOME MEASURES: Quality adjusted life years (QALYs) at one year and societal costs, estimated from patient reported utilities (UK and US EuroQol, SF-6D, and visual analogue scale) and diaries on costs (healthcare, patient’s costs, and productivity). RESULTS: Compared with prolonged conservative care, early surgery provided faster recovery, with a gain in QALYs according to the UK EuroQol of 0.044 (95% confidence interval 0.005 to 0.083), the US EuroQol of 0.032 (0.005 to 0.059), the SF-6D of 0.024 (0.003 to 0.046), and the visual analogue scale of 0.032 (–0.003 to 0.066). From the healthcare perspective, early surgery resulted in higher costs (difference €1819 (£1449; $2832), 95% confidence interval €842 to €2790), with a cost utility ratio per QALY of €41 000 (€14 000 to €430 000). From the societal perspective, savings on productivity costs led to a negligible total difference in cost (€–12, €–4029 to €4006). CONCLUSIONS: Faster recovery from sciatica makes early surgery likely to be cost effective compared with prolonged conservative care. The estimated difference in healthcare costs was acceptable and was compensated for by the difference in absenteeism from work. For a willingness to pay of €40 000 or more per QALY, early surgery need not be withheld for economic reasons. Trial registration Current Controlled Trials ISRCTN 26872154.

OBJECTIVE:s To evaluate the effects of early lumbar disc surgery compared with prolonged conservative care for patients with sciatica over two years of follow-up. Design Randomised controlled trial. Setting Nine Dutch hospitals. Participants 283 patients with 6-12 weeks of sciatica. Interventions Early surgery or an intended six months of continued conservative treatment, with delayed surgery if needed. MAIN OUTCOME MEASURES: Scores from Roland disability questionnaire for sciatica, visual analogue scale for leg pain, and Likert self rating scale of global perceived recovery. RESULTS: Of the 141 patients assigned to undergo early surgery, 125 (89%) underwent microdiscectomy. Of the 142 patients assigned to conservative treatment, 62 (44%) eventually required surgery, seven doing so in the second year of follow-up. There was no significant overall difference between treatment arms in disability scores during the first two years (P=0.25). Improvement in leg pain was faster for patients randomised to early surgery, with a significant difference between "areas under the curves" over two years (P=0.05). This short term benefit of early surgery was no longer significant by six months and continued to narrow between six months and 24 months. Patient satisfaction decreased slightly between one and two years for both groups. At two years 20% of all patients reported an unsatisfactory outcome. CONCLUSIONS: Early surgery achieved more rapid relief of sciatica than conservative care, but outcomes were similar by one year and these did not change during the second year. Trial Registry ISRCT No 26872154.

Autologous stem cell transplantation (ASCT) has been intensively investigated for treatment of patients with chronic lymphocytic leukemia (CLL) during recent years. To assess the potential therapeutic value of ASCT for CLL, the present article aims at answering the following crucial questions: (1) Does ASCT have curative potential? (2) What is the therapeutic potential of ASCT in terms of disease control in relation to toxicity? (3) What is the role of ASCT in the current arsenal of CLL treatment modalities? Evidence from clinical and minimal residual disease (MRD) studies suggests that ASCT has curative potential in only a few patients, if any. Nevertheless, ASCT might be capable of prolonged disease control even in CLL with poor-risk features. Uncontrolled prospective studies have indicated the superiority of ASCT over alkylator and fludarabine monotherapy but not necessarily over purine analogue cyclophosphamide or antibody combinations. A significant risk of secondary neoplasms, in particular myelodysplasias, has to be taken into account. Therefore, ASCT cannot be considered as standard treatment for CLL and should be performed only in the context of clinical trials.

Allogeneic stem cell transplantation (SCT) is the treatment of choice for the majority of young patients with myelodysplasia (MDS) who have a histocompatible donor (sibling or unrelated donor). For some patients lacking a human leukocyte antigen (HLA)-compatible donor, chemotherapy followed by autologous SCT may be a reasonable alternative, especially for patients with therapy-related MDS/acute myeloid leukemia (AML). A substantial number of candidates may not be eligible for autologous SCT due to failure to induce remission or failure to collect sufficient numbers of stem cells. Careful clinical evaluation of the prognostic factors, such as age, cytogenetic characteristics, chances of achieving complete remission (CR), and availability of a matched unrelated donor, may guide the treating physician in advising the patient about the available treatment options. Mobilized peripheral blood stem cells are the preferred stem cell source for young patients, especially in view of the more rapid hematopoietic recovery after transplantation with mobilized stem cells, but bone marrow stem cells also may be considered for patients older than 50 years. Further development of precise prognostic classification systems, including an accurate evaluation of cytogenetic/molecular response to chemotherapy, is needed to develop a risk-adapted strategy for individual patients.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Randomized studies testing the clinical efficacy of platelet additive solutions (PASs) for storage of platelets are scarce and often biased by patient selection. We conducted a multicenter, randomized study to investigate clinical efficacy of platelets stored in PAS II versus plasma, also including patients with clinical complications associated with increased platelet consumption. A total of 168 evaluable patients received pooled buffy coat–derived platelet concentrates (PCs) suspended in either plasma (n = 354) or PAS II (n = 411) stored up to 5 days. Both univariate as well as multivariate analysis showed a significant effect of used storage medium in regard to 1- and 24-hour count increments and corrected count increments, in favor of plasma PCs. However, there were no significant differences between the groups regarding bleeding complications and transfusion interval. Adverse transfusion reactions occurred significantly less after transfusions with PAS II PCs (P= .04). Multivariate analysis showed no significant effect of the used storage medium on the incidence of 1- and 24-hour transfusion failure. We showed safety and efficacy of PAS II PCs in intensively treated patients; however, plasma PCs show superior increments.

In this multicenter retrospective study, the outcomes of 836 patients with myelodysplastic syndrome (MDS) who underwent transplantation with a human leukocyte antigen (HLA)–identical sibling donor were analyzed according to 2 types of conditioning: reduced-intensity conditioning (RIC) in 215 patients, and standard myeloablative (or high-dose) conditioning (SMC) in 621 patients. In multivariate analysis, the 3-year relapse rate was significantly increased after RIC (hazard ratio [HR], 1.64; 95% confidence interval [95% CI], 1.2-2.2; P= .001), but the 3-year nonrelapse mortality (NRM) rate was decreased in the RIC group (HR, 0.61; 95% CI, 0.41-0.91; P= .015). The 3-year probabilities of progression-free and overall survivals were similar in both groups (39% after SMC vs 33% in RIC; multivariate P= .9; and 45% vs 41%, respectively; P= .8). In conclusion, the lower 3-year NRM after RIC is encouraging, since these patients were older (age > 50 years in 73% RIC vs 28% in SMC, P< .001) and had more adverse pretransplantation variables. However, based on the higher risk of relapse, patients with no contraindications for SMC should not receive RIC outside of prospective randomized trials, which are needed to establish the position of RIC-based transplantation in the treatment of patients with MDS.

Abstract: In this article, we explore the effect of the occurrence of a target sound on the force that is applied by the ear when listening at a surface because differences in applied force induce variation in carprints of a single ear. Forty two subjects each listened four times at a surface. During two of these listening efforts there was silence. While the subjects were listening, we measured the amount of force that was applied to the surface. To explore the effect of the occurrence of a target sound upon applied force, we applied a mixed model analysis of variance. The force applied by the ear appeared to be uncorrelated to presence or absence of a target sound. This lack of association appeared not to be the result of potential confounders. Only repetition (i.e., the position of a listening effort in the series of four), appeared to significantly affect applied force; this force being generally lower during a first listening effort.

Cytomegalovirus (CMV) has been a major cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). The importance of the recipient's serologic status is paramount. However, the importance of the donor's serologic status in CMV-seropositive recipients is controversial. We analyzed the influence of the donor's CMV status in a large cohort of patients. A total of 7018 patients seropositive for CMV reported to the European Group for Blood and Marrow Transplantation (EBMT) were included; 5910 patients had undergone HLA-identical sibling SCT and 1108 patients had undergone unrelated donor SCT. Univariate and multivariate proportional hazards models were constructed for survival, event-free survival, transplant-related mortality, and relapse incidence. Patients receiving grafts from CMV-seropositive HLA-identical sibling donors had the same survival as patients grafted from seronegative donors (hazard ratio [HR], 1.04; P = .37; 95% confidence interval [CI], 0.95-1.14). However, unrelated donor stem cell (SC) transplant recipients receiving grafts from CMV-seropositive donors had an improved 5-year survival (35% versus 27%; HR = 0.8; P = .006), an improved event-free survival (30% versus 22%; HR = 0.8; P = .01), and a reduced transplant-related mortality (49% versus 62%; HR = 0.7; P < .001). There was no influence on the relapse incidence. The effects of donor CMV status remained in multivariate analyses. The effect of donor status was different among different disease categories. In patients with chronic myelogenous leukemia (CML), T-cell depletion abrogated the beneficial effect of donor status, suggesting that the effect is mediated through transfer of donor immunity. Our data suggest that donor CMV status influences outcome of unrelated SCT. For a CMV-seropositive patient, a seropositive donor might be preferable. (Blood. 2003;102:4255-4260)

Hematopoietic stem cell transplantation (SCT) is the only proven cure for chronic myeloid leukemia (CML), a rare disease in childhood. We report outcomes of 314 children with Philadelphia-chromosome–positive (Ph+) CML undergoing SCT from HLA-matched siblings (n = 182) or volunteer-unrelated donors (VUD; n = 132). Three-year overall survival (OS) and leukemia-free survival (LFS) rates were 66% and 55% (n = 314). For 156 children in first chronic phase (CP1) who underwent transplantation from HLA-identical siblings, OS and LFS rates were 75% and 63%. For 97 children who underwent SCT in CP1 from VUD, 3-year OS and LFS rates were 65% and 56%, reflecting higher transplantation-related mortality (TRM) after VUD SCT (35% vs 20%; multivariate hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.0-3.5; P = .05). In a multivariate model for OS and LFS, outcomes were superior in CP1 than in advanced phase (AP/CP1) (OS HR, 2.0; 95% CI, 1.3-3; P = .001; LFS HR, 1.8; 95% CI, 1.2-2.6; P = .003). For relapse, donor source (VUD/sibling) (HR, 0.38; 95% CI, 0.19-0.76; P = .006) and disease stage (AP/CP1) (HR, 2.4; 95% CI, 1.36-4.3; P = .003) were significant. This is the first large series to show that SCT confers long-term LFS in most children with CML and helps assess alternative therapy, including tyrosine kinase inhibitors.

Graft-versus-host disease in its acute (aGvHD) or chronic form (cGvHD) remains the most important posttransplantation factor influencing outcome after allogeneic hematopoietic stem cell transplantation (HSCT). It increases transplantation-related mortality (TRM) but reduces risk of relapse. The net effect of these 2 discordant effects determines survival. In view of current interests to exploit graft-versus-leukemia (GVL) effects, we analyzed 4174 HLA-identical sibling transplantations for chronic myeloid leukemia in first chronic phase, depending on the presence or absence and severity of GvHD with a landmark analysis. During the first 100 days, only aGvHD grades III and IV had an impact on TRM. During the time period day 100 to 3 years increasing severity of aGvHD is associated with increased TRM and decreased relapse incidence (RI) with hazard ratios (HRs) for TRM as follows: grade 0, HR = 1.0; grade I, HR = 1.52 (1.19-1.96); grade II, HR = 2.48 (1.95-3.14); grade III, HR = 5.76 (4.44-7.48); grade IV, HR = 14.7 (10.9-19.9) and likewise for RI: grade I versus 0, HR = 0.94 (0.76-1.16); grade II, HR = 0.60 (0.46-0.77); grade III, HR = 0.48 (0.29-0.81); grade IV, HR = 0.14 (0.02-0.99). Beyond 3 years, TRM and RI are determined by cGvHD. Limited cGvHD reduces RI to the same extent as extensive cGvHD but has no impact on TRM and, hence, results in best survival with an HR = 0.48 (0.32-0.71). aGvHD grade I has the highest likelihood of subsequent limited cGvHD, which results in cumulative incidence estimates of survival at 10 years being best for patients with initial aGvHD grade I: survival at 10 years grade 0 = 59%, I = 63%, II = 56%, III = 26%, IV = not applicable. These data clarify the role of GvHD in posttransplantation outcome. Considerations for long-term outcome are essential when short-term data of interventions on GvHD are analyzed.

Donor lymphocyte infusion (DLI) can produce durable remissions in patients with chronic myelogenous leukemia (CML) who have a relapse after an allogeneic stem cell transplantation. However, the best modality to administer DLI is still unclear. The effect of the initial cell dose (ICD; ie, mononuclear cells × 108/kg received in the first instance) on outcome was retrospectively analyzed in 298 of 344 patients treated with DLI at 51 centers. Patients were classified into 3 groups according to the ICD: 98 in group A (≤ 0.20), 107 in group B (0.21-2.0), and 93 in group C (> 2.0). Additional infusions were given to 62%, 20%, and 5% of patients in groups A, B, and C, respectively. A lower ICD was associated with less graft-versus-host disease (GVHD; A, 26%; B, 53%; C, 62%;P < .001), less myelosuppression (A, 10%; B, 23%; C, 24%; P = .01), and similar response rate (A, 78%; B, 73%; C, 70%; P = .48). Nonadjusted estimates of 3-year survival, failure-free survival, and DLI-related mortality were 84%, 66%, and 5% respectively, in group A; 63%, 57%, and 20% in group B; and 58%, 45%, and 22% in group C. Outcome analysis was adjusted for patient age, donor type, sex of donor, sex mismatch, disease phase at transplantation, T-cell depletion, interval from transplantation to DLI, GVHD prior to relapse, relapse type, and date of DLI. After adjustment, lower ICD was associated with less GVHD, less myelosuppression, same response rate, better survival, better failure-free survival, and less DLI-related mortality. Our results suggest that the first DLI dose should not exceed 0.2 × 108 mononuclear cells/kg.

In this multicenter retrospective study, the outcomes of 234 patients with myelodysplastic syndrome (MDS) who underwent transplantation between 1995 and 1999 from HLA-identical siblings were analyzed according to the hematopoietic stem cell source used, that is, bone marrow (BM, n = 132) or granulocyte colony-stimulating factor–mobilized peripheral blood progenitor cells (PBPCs, n = 102). There were 69 cases of refractory anemia (RA), 86 RA with excess blasts (RAEB), 75 RAEB in transformation (RAEB-t), and 4 unclassified MDS at diagnosis. The International Prognostic Scoring System was intermediate-2 or high in 104 of the 158 available scores. Multivariate analyses focused on transplantation-related mortality (TRM), 2-year treatment failure incidence, and survival. Use of PBPCs reduced the median duration of neutropenia and thrombocytopenia by 4 and 12 days, respectively. The incidence of acute GVHD was similar whatever the graft type used. Chronic GVHD was more likely to have occurred with PBPCs (odds ratio [OR], 1.62; 95% confidence interval [CI], 0.87-3.02). Two-year TRM was significantly reduced with PBPCs (relative risk [RR], 0.33; 95% CI, 0.15-0.73; P < .007), except for patients who had either RA or high-risk cytogenetics. The 2-year treatment failure incidence was significantly decreased with PBPCs, from 38% to 13% (RR, 0.22; 95% CI, 0.10-0.48;P < .001). Estimate of the 2-year event-free survival was 50% with PBPCs versus 39% with BM. In multivariate analysis, the outcome was significantly improved with PBPCs (RR, 0.27; 95% CI, 0.13-0.52; P < .001), except for patients with either RA or high-risk cytogenetics. In conclusion, PBPCs might be preferred for allogeneic transplantation in MDS patients at high risk for relapse on the basis of morphologic criteria because the use of this hematopoietic stem cell was associated with lower treatment failure incidence and improved survival.

Preterm neonates frequently develop nephrocalcinosis (NC). However, the cause has not yet been elucidated. This study focuses on the effects of urine from preterm neonates on crystallization kinetics. Urine samples were collected and renal ultrasound examinations of preterm neonates (gestational age < 32 weeks) were performed during the first weeks of life, at term, and ages 6, 12, and 24 months. The effect of urine on crystallization was determined using a seeded crystal growth system, which measures the square root of solubility product (√Lc), percentage of growth inhibition (GI), and agglomeration inhibition ([tm]) of calcium oxalate crystals. Data for preterm neonates in the first weeks of life (n = 19) were compared with those for full-term neonates (n = 17) and healthy adults. Moreover, the correlation between [tm] and urinary (U)citrate level was studied. Mean √Lc (0.27 ± 0.1 versus 0.36 ± 0.08 mmol/L) and mean [tm] (81 ± 32 versus 143 ± 97 minutes) were lower and mean Ucalcium-creatinine (2.20 ± 1.74 versus 0.46 ± 0.73 mol/mol) and Uoxalate-creatinine ratios (0.39 ± 0.21 versus 0.16 ± 0.09 mol/mol) were greater in preterm neonates in the first weeks of life compared with full-term neonates (p < 0.05). Furthermore, [tm] was less than the lower limit for healthy adults for all but one preterm neonate; [tm] increased and Ucalcium-creatinine and Uoxalate-creatinine ratios decreased with age (p < 0.005). There was a correlation between [tm] and citrate excretion (coefficient of 38; P< 0.001). Patients with and without NC at term did not differ statistically in mean √Lc, percentage of GI, or [tm]. In conclusion, urine from preterm neonates in the first weeks of life is highly supersaturated and has a defective ability to inhibit calcium oxalate crystal agglomeration. This ability improves with age and is citrate mediated. We suggest that both the high level of supersaturation and defective ability to inhibit calcium oxalate crystal agglomeration contribute to the high incidence of NC. © 2001 by the National Kidney Foundation, Inc.

Decreased life expectancy may occur after remote peptic ulcer surgery, but the cause of shortened survival is unclear. A 50-year follow-up study of an Amsterdam cohort of postgastrectomy patients who underwent ulcer surgery between 1931 and 1960 showed a statistically significant decrease in survival after a postoperative interval of 12 years or more compared with the general population. The shortened life expectancy mainly reflected decreased survival in men. In women, no significant difference in survival compared with the general population was observed. The excess mortality in men was predominantly due to a statistically significant increase in cancer-related deaths. Carcinoma of the lung accounted for the majority of excess mortality. No time relationship between lung cancer death and interval since surgery was observed. Thus, smoking, primarily in men who had undergone surgery for gastric ulcers, seems an important factor contributing to excess mortality and shortened life expectancy. Excess mortality due to tobacco use has also been observed in postmarketing surveillance of H2-receptor antagonists. Therefore, smoking cessation may provide the greatest improvement in the long-term prognosis of peptic ulcer patients, regardless of the treatment.