Novel agents including proteasome inhibitors and immunomodulatory drugs are now routinely utilized as part of the induction regimen before transplantation and this has resulted in substantial ...improvements in the depth of response achieved before transplant. Given that depth of response is prognostic for overall outcome, a number of studies have been conducted or are ongoing to investigate the use of novel agents as consolidation and maintenance therapy after transplant. Most clinical trials have reported after consolidation and maintenance therapy an increased PFS and even overall survival in some of them. The use of post-autologous stem cell transplant consolidation and maintenance is an increasingly attractive concept. However, some side effects could be observed with such long-term therapy and many open questions are still under debate. The decision to administer consolidation and/or maintenance therapy will likely need to be guided by the individual patient situation. This review aims to analyze the currently available research evidence in this field.
Objective: Does the use of bilateral internal thoracic artery (ITA) grafts provide incremental benefit relative to the use of a single ITA graft?
Methods: We conducted a retrospective, nonrandomized, ...long-term (mean follow-up interval of 10 postoperative years) study of patients undergoing elective primary isolated coronary bypass surgery who received either single (8123 patients) or bilateral ITA grafts (2001 patients), with or without additional vein grafts. Multiple statistical methods including propensity score matching, and multivariable parsimonious and nonparsimonious risk factor analyses were used to address the issues of patient selection and heterogeneity.
Results: In-hospital mortality was 0.7% for both the bilateral and single ITA groups. Survival for the bilateral ITA group was 94%, 84%, and 67%, and for the single ITA group 92%, 79%, and 64% at 5, 10, and 15 postoperative years, respectively (
P < .001). Death, reoperation, and percutaneous transluminal coronary angioplasty were more frequent for patients undergoing single rather than bilateral ITA grafting, and this observation remained true despite multiple adjustments for patient selection, sampling, and length of follow-up. The differences between the bilateral and single ITA groups were greatest in regard to reoperation. The extent of benefit of bilateral ITA grafting varied according to patient-related variables, but no patient subsets were identified for whom single ITA grafting could be predicted to provide an advantage.
Conclusions: Patients who received 2 ITA grafts had decreased risks of death, reoperation, and angioplasty. (J Thorac Cardiovasc Surg 1999;117:855-72)
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•X-ray scattering experiments were performed on DMPC with and without halothane.•Molecular dynamics simulations were performed on similar systems.•Halothane causes an increase in DMPC ...chain spacing.•Pressure causes a reduction in DMPC chain spacing.
Using a combination of high pressure wide angle X-ray scattering experiments and molecular dynamics simulations, we probe the effect of the archetypal general anaesthetic halothane on the lipid hydrocarbon chain packing and ordering in model bilayers and the variation in these parameters with pressure. Incorporation of halothane into the membrane causes an expansion of the lipid hydrocarbon chain packing at all pressures. The effect of halothane incorporation on the hydrocarbon chain order parameter is significantly reduced at elevated pressure.
•Pain catastrophizing is associated with the fear of overwhelming labor pain.•Its association with pain, analgesic use, and maternal recovery is unknown.•High catastrophizers reported greater pain ...when requesting labor analgesia.•They did not have higher labor and postpartum pain or analgesic use.•They did report feeling less comfort, ability to mobilize and control at discharge.
Pain catastrophizing is an exaggerated negative orientation to painful stimuli which in obstetric patients is associated with fear of overwhelming labor pain and negative pain-related outcomes. This study aimed to quantitatively examine the association of pain catastrophizing with maternal labor pain outcomes.
We conducted a prospective observational study of women admitted for a vaginal trial of labor. Subjects completed the 13-item Pain Catastrophizing scale (PCS) questionnaire (scored 0 to 52, higher scores representing greater catastrophizing). Pain was assessed at baseline and at request for neuraxial labor analgesia. Labor and postpartum pain intensity was assessed as the average area under the pain intensity by time curve. Pain at request for analgesia, labor pain, postpartum pain, analgesic consumption, and quality of recovery was compared between high (PCS ≥ 17) and low catastrophizing groups.
Data from 138/157 (88%) subjects were included in the analysis. Median (IQR) pain scores at request for analgesia were 9 (8,10) and 8 (6,9), a difference of 1 (95% CI 0 to 2.5, P = 0.008) in high-catastrophizing and in low-catastrophizing groups, respectively. Adjusted pain during labor, postpartum pain and opioid analgesic use were not significantly different. High-catastrophizers reported less comfort, ability to mobilize and less control during hospitalization. Post-discharge there were no differences in pain or analgesic use.
We did not observe greater labor or post-delivery pain or increased analgesic use in high-catastrophizing parturients. High catastrophizers reported greater pain when requesting analgesia, which is consistent with the role of catastrophizing in intensifying the experience of pain.
To study the molecular epidemiology of vancomycin-resistant Enterococcus (VRE) colonization and to identify modifiable risk factors among patients with hematologic malignancies.
A hematology-oncology ...unit with high prevalence of VRE colonization.
Patients with hematologic malignancies and hematopoietic stem cell transplantation recipients admitted to the hospital.
Patients underwent weekly surveillance by means of perianal swabs for VRE colonization and, if colonized, were placed in contact isolation. We studied the molecular epidemiology in fecal and blood isolates by pulsed-field gel electrophoresis over a 1-year period. We performed a retrospective case-control study over a 3-year period. Cases were defined as patients colonized by VRE, and controls were defined as patients negative for VRE colonization. Case patients and control patients were matched by admitting service and length of observation time.
Molecular genotyping demonstrated the primarily polyclonal nature of VRE isolates. Colonization occurred at a median of 14 days. Colonized patients were characterized by longer hospital admissions. Previous use of ceftazidime was associated with VRE colonization (P < .001), while use of intravenous vancomycin and antibiotics with anaerobic activity did not emerge as a risk factor. There was no association with neutropenia or presence of colonic mucosal disruption, and severity of illness was similar in both groups.
Molecular studies showed that in the majority of VRE-colonized patients the strains were unique, arguing that VRE acquisition was sporadic rather than resulting from a common source of transmission. Patient-specific factors, including prior antibiotic exposure, rather than breaches in infection control likely predict for risk of fecal VRE colonization.
MTX is a standard component of acute GVHD prophylaxis. However, its use can be limited by toxicity. On the basis of disease risk, we prospectively assigned 132 consecutive patients from January 2005 ...to February 2011 undergoing first allogeneic hematopoietic cell transplant after conditioning with fludarabine and melphalan to acute GVHD prophylaxis with tacrolimus/MTX (TAC/MTX, N=22), TAC/micro-dose MTX/mycophenolate mofetil (TAC/μMTX/MMF, N=78) or TAC/MMF (TAC/MMF, N=32), to optimize acute GVHD prevention and decrease mortality. The median (range) follow-up was 24 (0.8-60) months. The median patient ages (range) were 37 (23-63), 56 (20-68) and 54 (22-68) years (P<0.0001) for TAC/MTX, TAC/μMTX/MMF and TAC/MMF, respectively. The 100-day cumulative incidences of grade III-IV acute GVHD were 19, 23 and 49% (P=0.015), respectively. The cumulative incidences of severe chronic GVHD at 1 year were 38, 29 and 79% (P<0.001), respectively. Regimen-related toxicities were not significantly different among the three prophylaxis regimens. PFS and OS were equivalent between the TAC/MTX and TAC/μMTX/MMF arms despite significantly older patients in the latter arm, and both had superior PFS and OS than the TAC/MMF arm. Acute GVHD prophylaxis with TAC/μMTX/MMF is as effective as TAC/MTX and superior to TAC/MMF.
Although meal replacement can lead to weight reduction, there is uncertainty whether this dietary approach implemented into a lifestyle programme can improve long-term dietary intake. In this ...subanalysis of the
(ACOORH) study (
= 463), participants with metabolic risk factors were randomly assigned to either a meal replacement-based lifestyle intervention group (INT) or a lifestyle intervention control group (CON). This subanalysis relies only on data of participants (
= 119) who returned correctly completed dietary records at baseline, and after 12 and 52 weeks. Both groups were not matched for nutrient composition at baseline. These data were further stratified by sex and also associated with weight change. INT showed a higher increase in protein intake related to the daily energy intake after 12 weeks (+6.37% 4.69; 8.04 vs. +2.48% 0.73; 4.23,
< 0.001) of intervention compared to CON. Fat and carbohydrate intake related to the daily energy intake were more strongly reduced in the INT compared to CON (both
< 0.01). After sex stratification, particularly INT-women increased their total protein intake after 12 (INT: +12.7 g vs. CON: -5.1 g,
= 0.021) and 52 weeks (INT: +5.7 g vs. CON: -16.4 g,
= 0.002) compared to CON. Protein intake was negatively associated with weight change (r = -0.421;
< 0.001) after 12 weeks. The results indicate that a protein-rich dietary strategy with a meal replacement can improve long-term nutritional intake, and was associated with weight loss.
To assess the impact of spleen status on engraftment, and early morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT), we analyzed 9,683 myeloablative allograft recipients ...from 1990 to 2006; 472 had prior splenectomy (SP), 300 splenic irradiation (SI), 1,471 with splenomegaly (SM), and 7,440 with normal spleen (NS). Median times to neutrophil engraftment (NE) and platelet engraftment (PE) were 15 vs 18 days and 22 vs 24 days for the SP and NS groups, respectively (P<0.001). Hematopoietic recovery at day +100 was not different across all groups, however the odds ratio of days +14 and +21 NE and day +28 PE were 3.26, 2.25 and 1.28 for SP, and 0.56, 0.55, and 0.82 for SM groups compared to NS (P<0.001), respectively. Among patients with SM, use of peripheral blood grafts improved NE at day +21, and CD34+ cell dose >5.7 × 10(6)/kg improved PE at day+28. After adjusting variables by Cox regression, the incidence of GVHD and OS were not different among groups. SM is associated with delayed engraftment, whereas SP prior to HCT facilitates early engraftment without having an impact on survival.
The international staging system (ISS) for multiple myeloma (MM) is a validated alternative to the Durie-Salmon staging system (DSS) for predicting survival at diagnosis. We compared these staging ...systems for predicting outcomes after upfront autologous stem cell transplantation by analyzing the outcomes of 729 patients between 1995 and 2002. With a median follow-up of 56 months, the univariate probabilities (95% CI) of non-relapse mortality (NRM), relapse, progression-free survival (PFS) and overall survival (OS) at 5 years were 7, 68, 25 and 52%, respectively. The median OS for stages I, II, III by DSS and ISS were 82, 68, 50 and 64, 68, 45 months, respectively. The concordance between the two staging systems was only 36%. Staging systems were formally compared using Cox models fit with DSS and ISS stages. The relative risks of PFS and OS were significantly different for stages I vs II and II vs III for DSS, but only for stages II vs III for ISS. Although both systems were predictive of PFS and OS, the DSS was superior in formal statistical comparison using Brier score. However, neither system was strongly predictive of outcomes, indicating the need for newer schemes incorporating other prognostic markers.
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