Islet transplantation is a promising therapy used to achieve glycometabolic control in a select subgroup of individuals with type I diabetes. However, features that characterize human islet isolation ...success prior to transplantation are not standardized and lack validation. We conducted a retrospective analysis of 806 isolation records from 14 pancreas‐processing laboratories, considering variables from relevant studies in the last 15 years. The outcome was defined as postpurification islet equivalent count, dichotomized into yields ≥315 000 or ≤220 000. Univariate analysis showed that donor cause of death and use of hormonal medications negatively influenced outcome. Conversely, pancreata from heavier donors and those containing elevated levels of surface fat positively influence outcome, as did heavier pancreata and donors with normal amylase levels. Multivariable logistic regression analysis identified the positive impact on outcome of surgically intact pancreata and donors with normal liver function, and confirmed that younger donors, increased body mass index, shorter cold ischemia times, no administration of fluid/electrolyte medications, absence of organ edema, use of University of Wisconsin preservation solution and a fatty pancreas improves outcome. In conclusion, this multicenter analysis highlights the importance of carefully reviewing all donor, pancreas and processing parameters prior to isolation and transplantation.
Data analysis from 14 islet processing facilities revealed that surgically intact pancreata from hemodynamically stable young donors with elevated BMI, short cold‐ischemia time and preserved in UW solution strongly correlated with successful human islet isolation.
To evaluate the incidence and associated risk factors of solid cancers after bone marrow transplantation (BMT).
We analyzed 2,129 patients who had undergone BMT for hematologic malignancies at the ...City of Hope National Medical Center between 1976 and 1998. A retrospective cohort and nested case-control study design were used to evaluate the role of pretransplantation therapeutic exposures and transplant conditioning regimens.
Twenty-nine patients developed solid cancers after BMT, which represents a two-fold increase in risk compared with a comparable normal population. The estimated cumulative probability (+/- SE) for development of a solid cancer was 6.1% +/- 1.6% at 10 years. The risk was significantly elevated for liver cancer (standardized incidence ratio SIR, 27.7; 95% confidence interval CI, 1.9 to 57.3), cancer of the oral cavity (SIR, 17.4; 95% CI, 6.3 to 34.1), and cervical cancer (SIR, 13.3; 95% CI, 3.5 to 29.6). Each of the two patients with liver cancer had a history of chronic hepatitis C infection. All six patients with squamous cell carcinoma of the skin had chronic graft-versus-host disease. The risk was significantly higher for survivors who were younger than 34 years of age at time of BMT (SIR, 5.3; 95% CI, 2.7 to 8.6). Cancers of the thyroid gland, liver, and oral cavity occurred primarily among patients who received total-body irradiation.
The risk of radiation-associated solid tumor development after BMT is likely to increase with longer follow-up. This underscores the importance of close monitoring of patients who undergo BMT.
We analyzed data on 612 patients who had undergone high-dose chemoradiotherapy (HDT) with autologous stem cell rescue for Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) at the City of Hope ...National Medical Center, to evaluate the incidence of therapy-related myelodysplasia (t-MDS) or therapy-related acute myeloid leukemia (t-AML) and associated risk factors. A retrospective cohort and a nested case-control study design were used to evaluate the role of pretransplant therapeutic exposures and transplant conditioning regimens. Twenty-two patients developed morphologic evidence of t-MDS/t-AML. The estimated cumulative probability of developing morphologic t-MDS/t-AML was 8.6% ± 2.1% at 6 years. Multivariate analysis of the entire cohort revealed stem cell priming with VP-16 (RR = 7.7, P = 0.002) to be independently associated with an increased risk of t-MDS/t-AML. The influence of pretransplant therapy on subsequent t-MDS/t-AML risk was determined by a case-control study. Multivariate analysis revealed an association between pretransplant radiation and the risk of t-MDS/t-AML, but failed to reveal any association with pretransplant chemotherapy or conditioning regimens. However, patients who had been primed with VP-16 for stem cell mobilization were at a 12.3-fold increased risk of developing t-AML with 11q23/21q22 abnormalities (P = 0.006). Patients undergoing HDT with stem cell rescue are at an increased risk of t-MDS/t-AML, especially those receiving priming with VP-16 for peripheral stem cell collection.
Background: Ongoing clinical trials are addressing the accuracy and safety of sentinel node biopsy (SNB) in the treatment of breast cancer; however, SNB is already increasingly being used in clinical ...practice. This study examined the extent and time trends of the use of SNB in stage I and II breast cancer patients. Methods: Clinical data were collected from stage I and II (tumor size ⩽5.0 cm) breast cancer patients (n = 3003) who were treated at five comprehensive cancer centers between July 1, 1997, and December 31, 2000. Axillary surgery was classified as SNB alone, SNB + axillary node dissection (AND), AND alone, or none. Patterns of use of axillary surgery were summarized as the percentage of patients receiving each surgery type. The statistical significance of time trends for the use of SNB alone was analyzed by logistic regression models. All statistical tests were two-sided. Results: Overall, SNB alone was used in 13% of patients, SNB + AND in 22%, AND alone in 59%, and no axillary surgery in 6%. Use of SNB alone was statistically significantly associated with breast-conserving surgery of both smaller (⩽2 cm) and larger tumors (2–5 cm) (P<.001 for both associations). For stage I cancer patients treated with breast-conserving surgery (n = 1763), use of SNB increased statistically significantly over the study period, from 8% in 1997 to 9%, 14%, 15%, 22%, 42%, and 58% for the next six consecutive 6-month time intervals, respectively. After controlling for center, age, and comorbidity, the odds ratio for the use of SNB alone was 2.30 (95% confidence interval = 1.88 to 2.82) for each 6-month interval (P<.001). Conclusions: Widespread use of SNB outside the clinical trial setting suggests that oncologists at cancer centers in our study have accepted SNB as standard-of-care for the treatment of breast cancer. This acceptance, if it occurs in other cancer centers and community practice, may affect accrual and generalizability of ongoing clinical trials of SNB.
Benchmark data regarding quality measures of breast cancer management are needed. We investigated rates of radiation use after breast conservation therapy (BCT) for patients treated for ductal ...carcinoma-in-situ (DCIS) or invasive breast cancer at National Comprehensive Cancer Network (NCCN) centers.
We studied 3,333 consecutive patients treated between 1997 and 2002 with BCT for DCIS (n = 587) or for stage I or II breast cancer (n = 2,746) in eight NCCN centers.
The overall rate of radiation therapy use was 91%, with a lower frequency of radiation use in DCIS versus invasive breast cancers (82% v 94%; odds ratio OR = 0.31; P < .0001). In a multivariable analysis of the patients with DCIS, the only factor significantly associated with lower rates of radiation use was low/intermediate grade (OR = 0.19; P = .0003). For patients with invasive breast cancer, significant factors were presence of comorbidity (OR = 0.53; P = .0005), tubular histology (OR = 0.39; P = .02), type of health insurance (P = .0072), and the NCCN institution (P = .0005). The model also showed lower rates of radiation use in patients with stage II disease who did not receive systemic therapy (OR = 0.01; P = .0001), younger patients who did not receive systemic therapy (P = .003); and older patients with stage I disease (P < .0001).
Radiation use as a component of BCT was high for patients seen at NCCN centers; however, there was variability in practice patterns noted across institutions. Radiation was most commonly omitted in patients with favorable disease characteristics, patients with comorbidities, and patients who also did not receive guideline-recommended systemic treatment.
High impact forces during running have been associated with tibial stress injuries. Previous research has demonstrated increasing step rate will decrease impact forces during running. However, no ...research has determined the cognitive demand of gait retraining. The primary purpose was to determine the cognitive demand and effectiveness of field-based gait retraining. We hypothesized that in-field gait retraining would alter running mechanics without increasing cognitive workload as measured by EEG following learning. Runners with a history of tibial injury completed a gait retraining protocol which included a baseline run, retraining phase, practice phase, and re-assessment following retraining protocol. Results demonstrated an increase in the theta, beta, and gamma power within prefrontal cortex during new learning and corresponding return to baseline following skill acquisition and changes across alpha, beta, gamma, mu, and theta in the motor cortex (p < .05). In the midline superior parietal cortex, spectral power was greater for theta activity during new learning with a corresponding alpha suppression. Overall, the results demonstrated the use of EEG as an effective tool to measure cognitive demand for implicit motor learning and the effectiveness of in-field gait retraining.
We assayed IL-6 in 105 cerebrospinal fluid (CSF) samples from patients with ALS, MS, HTLV-1 associated myelopathy (HAM), and controls. There was considerable overlap in IL-6 levels in all patient ...groups. The mean IL-6 in 27 patients with ALS was significantly higher than in 21 patients in the other neurological disease (OND) group (
P=0.0075). There were no significant differences in MS or HAM and the OND control group. Overall, CSF IL-6 correlated with protein concentration but not with percentage IgG or IgG-albumin index. Patients with CSF oligoclonal bands were no more likely to have detectable IL-6 than patients without oligoclonal bands. Similarly, IL-6 did not correlate with clinical disease activity in MS when subgroups of patients were compared or when an individual patient was followed over time. The elevated IL-6 in ALS may reflect an ongoing humoral immune response, or IL-6 may be non-specifically expressed in these patients as a putative neurotrophic factor in response to nerve cell degeneration.
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