Family Mismatched Allogeneic Stem Cell Transplantation for Myelofibrosis: Report from the Chronic Malignancies Working Party of European Society for Blood and Marrow Transplantation

This analysis included 56 myelofibrosis (MF) patients transplanted from family mismatched donor between 2009 and 2015 enrolled in the European Society for Blood and Marrow Transplantation database. The median age was 57years (range, 38 to 72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34⁺ cell dose was 4.8?×?10⁶/kg (range, 1.7 to 22.9; n?=?43). Conditioning was predominantly myeloablative in 70% and reduced intensity in the remainder. Regimens were heterogeneous with thiotepa, busulfan, fludarabine, and post-transplant cyclophosphamide used in 59%. The incidence of neutrophil engraftment by 28days was 82% (range, 70% to 93%), at a median of 21days (range, 19 to 23). At 2years the cumulative incidence of primary graft failure was 9% (95% CI 1% to 16%) and secondary graft failure was 13% (95% CI 4% to 22%). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV was 28% (95% CI 16% to 40%) and 9% (95% CI 2% to 17%) at 100days. The cumulative incidence of chronic GVHD at 1 year was 45% (95% CI 32% to 58%), but the cumulative incidence of death without chronic GVHD by 1 year was 20% (95% CI 10% to 31%). With a median follow-up of 32 months, the 1- and 2-year overall survival was 61% (95% CI 48% to 74%) and 56% (95% CI 41% to 70%), respectively. The 1- and 2- year progression-free survival was 58% (95% CI 45% to 71%) and 43% (95% CI 28% to 58%), respectively, with a 2-year cumulative incidence of relapse of 19% (95% CI 7% to 31%). The 2-year nonrelapse mortality was 38% (95% CI 24% to 51%). This retrospective study of MF allo-SCT using family mismatched donors demonstrated feasibility of the approach, timely neutrophil engraftment in over 80% of cases, and acceptable overall and progression-free survival rates with relapse rates not dissimilar to the unrelated donor setting. However, strategies to minimize the risk of graft failure and the relatively high nonrelapse mortality need to be used, ideally in a multicenter prospective fashion.     

Palliative or curative treatment intent affects communication in radiation therapy consultations

OBJECTIVE: To assess whether communication in radiotherapy consultations is affected by palliative or curative treatment intent. SUBJECTS AND METHODS: The study involved 160 patients and 8 radiation oncologists. Eighty patients visited the radiation oncologist (RO) for palliative treatment and 80 for curative treatment. The consultation prior to radiation treatment was analyzed with the Roter Interaction Analysis System (RIAS). Within three days, patients completed a quality of life questionnaire (EORTC-QLQ-C30). RESULTS: In palliative radiotherapy (PRT) consultations, ROs asked more (closed-ended) biomedical and psychosocial questions and provided more information on prognosis than in consultations for curative radiotherapy (CRT). Patients in both groups provided a great deal of psychosocial information but asked few questions. The ROs expressed more concerns in the PRT consultations, while patients did not. PRT patients received fewer supportive remarks than CRT patients. In both groups, explicit decision-making received little attention. Proxies who accompanied the patients took a more active role in PRT than in CRT consultations. CONCLUSION: Communication in radiotherapy is affected by treatment intent with respect to the main contents of the consultation.     

Effects of a single‐dose methylphenidate challenge on resting‐state functional connectivity in stimulant‐treatment naive children and adults with ADHD

Prior studies suggest that methylphenidate, the primary pharmacological treatment for attention‐deficit/hyperactivity disorder (ADHD), alters functional brain connectivity. As the neurotransmitter systems targeted by methylphenidate undergo significant alterations throughout development, the effects of methylphenidate on functional connectivity may also be modulated by age. Therefore, we assessed the effects of a single methylphenidate challenge on brain network connectivity in stimulant‐treatment naïve children and adults with ADHD. We obtained resting‐state functional MRI from 50 boys (10–12 years of age) and 49 men (23–40 years of age) with ADHD (DSM IV, all subtypes), before and after an oral challenge with 0.5 mg/kg methylphenidate; and from 11 boys and 12 men as typically developing controls. Connectivity strength (CS), eigenvector centrality (EC), and betweenness centrality (BC) were calculated for the striatum, thalamus, dorsal anterior cingulate cortex (dACC), and prefrontal cortex (PFC). In line with our hypotheses, we found that methylphenidate decreased measures of connectivity and centrality in the striatum and thalamus in children with ADHD, but increased the same metrics in adults with ADHD. Surprisingly, we found no major effects of methylphenidate in the dACC and PFC in either children or adults. Interestingly, pre‐methylphenidate, participants with ADHD showed aberrant connectivity and centrality compared to controls predominantly in frontal regions. Our findings demonstrate that methylphenidate''s effects on connectivity of subcortical regions are age‐dependent in stimulant‐treatment naïve participants with ADHD, likely due to ongoing maturation of dopamine and noradrenaline systems. These findings highlight the importance for future studies to take a developmental perspective when studying the effects of methylphenidate treatment.     

A prospective study comparing the predictions of doctors versus models for treatment outcome of lung cancer patients: A step toward individualized care and shared decision making

Background

Decision Support Systems, based on statistical prediction models, have the potential to change the way medicine is being practiced, but their application is currently hampered by the astonishing lack of impact studies. Showing the theoretical benefit of using these models could stimulate conductance of such studies. In addition, it would pave the way for developing more advanced models, based on genomics, proteomics and imaging information, to further improve the performance of the models.

Purpose

In this prospective single-center study, previously developed and validated statistical models were used to predict the two-year survival (2yrS), dyspnea (DPN), and dysphagia (DPH) outcomes for lung cancer patients treated with chemo radiation. These predictions were compared to probabilities provided by doctors and guideline-based recommendations currently used. We hypothesized that model predictions would significantly outperform predictions from doctors.

Materials and methods

Experienced radiation oncologists (ROs) predicted all outcomes at two timepoints: (1) after the first consultation of the patient, and (2) after the radiation treatment plan was made. Differences in the performances of doctors and models were assessed using Area Under the Curve (AUC) analysis.

Results

A total number of 155 patients were included. At timepoint #1 the differences in AUCs between the ROs and the models were 0.15, 0.17, and 0.20 (for 2yrS, DPN, and DPH, respectively), with p-values of 0.02, 0.07, and 0.03. Comparable differences at timepoint #2 were not statistically significant due to the limited number of patients. Comparison to guideline-based recommendations also favored the models.

Conclusion

The models substantially outperformed ROs’ predictions and guideline-based recommendations currently used in clinical practice. Identification of risk groups on the basis of the models facilitates individualized treatment, and should be further investigated in clinical impact studies.     

Modeling severely discordant hematocrits and normal amniotic fluids after incomplete laser therapy in twin-to-twin transfusion syndrome

Our objective was to explain the clinical presentations of sustained arteriovenous anastomotic transfusion of blood after incomplete laser therapy in twin-to-twin transfusion syndrome (TTTS). We extended our mathematical model of TTTS by adding the dynamics of hematocrit, and simulated incomplete laser therapy, first, by leaving one patent opposite arteriovenous anastomosis from the recipient to the donor and, second, by leaving one patent arteriovenous anastomosis from the donor to the recipient. In both simulations we reproduced the clinical observation of severe hematocrit discordance preceding delayed amniotic fluid imbalance. In conclusion, incomplete laser therapy may cause a severe circulatory imbalance between the twins which presents predominantly as discordant hematocrits rather than discordant amniotic fluid volumes as in primary TTTS. These results imply that the anemia-polycythemia sequence is a sensitive mechanism to identify transfusion reversal after complicated laser therapy, confirming the suggested role of middle cerebral artery peak systolic velocity Doppler measurements as a useful method of follow-up.     

The impact of an additional ecotoxicity test on ecological quality standards

The present study aims to support decisions on whether or not to perform an extra toxicity test in order to improve environmental quality standards (EQSs). The impact of an additional ecotoxicity test was analyzed by predicting new ecotoxicity values with three different estimation methods and adding them to existing species sensitivity distributions (SSDs) on which the EQSs are based. The results show that EQSs are likely to increase due to increasing sample size, but the change also depends on the number of toxicity values available, the estimation method used and the representativeness of the species tested. The management consequences are illustrated in a case study on contaminated freshwater sediment in the Netherlands. It is shown that a slight increase of the EQS can result in a large reduction of sediment remediation costs without impairing regulatory protection levels. The paper identifies indicators that can be used to evaluate the potential impact of an extra ecotoxicity test.     

Traumatic Epidermal Inclusion Cyst After Minimally Invasive Surgery of a Displaced Intra-Articular Calcaneal Fracture: A Case Report

Epidermal inclusion cysts are common epithelial cysts of the skin. The latter classically originate from progressive cystic ectasia of the infundibular portion of hair follicle. Therefore, these cysts are usually found in hairy regions and rarely in glabrous skin such as the palms and soles. The etiology of glabrous epidermal inclusion cysts appear to be different from that of those located in hairy regions. It has been suggested that implantation of epithelial cells into subcutaneous tissue, such as during trauma, is most likely the pathophysiologic basis. Epidermal inclusion cysts on the palms and soles are often misdiagnosed, leading to improper treatment. Therefore, we report a rare case of an epidermal inclusion cyst of the heel after minimally invasive surgery of a displaced intra-articular calcaneal fracture.     

Changes in Circulating Levels of 25-hydroxyvitamin D3 in Breast Cancer Patients Receiving Chemotherapy

Cancer treatments, toxicities and their effects on lifestyle, may impact levels of vitamin D. The aim of this study was to determine serum 25-hydroxyvitamin D3 (25(OH)D₃) levels before, directly after and 6 months after chemotherapy in breast cancer patients (n?=?95), and a comparison group of women (n?=?52) not diagnosed with cancer. Changes in 25(OH)D₃ levels over time were compared using linear mixed models adjusted for age and season of blood sampling. Before start of chemotherapy, 25(OH)D₃ levels were lower in patients (estimated marginal mean 55.8?nmol/L, 95% confidence interval (95%CI) 51.2–60.4) compared to the comparison group (67.2?nmol/L, 95%CI 61.1–73.3, P?=?0.003). Directly after chemotherapy, 25(OH)D₃ levels were slightly decreased (–5.1?nmol/L, 95%CI –10.7–0.5, P?=?0.082), but ended up higher 6 months after chemotherapy (10.9?nmol/L, 95%CI 5.5–16.4, P?<?0.001) compared to pre-chemotherapy values. In women without cancer, 25(OH)D₃ levels remained stable throughout the study. Use of dietary supplements did not explain recovery of 25(OH)D₃ levels after chemotherapy. We reported lower 25(OH)D₃ levels in breast cancer patients, which decreased during chemotherapy, but recovered to levels observed in women without cancer within 6 months after chemotherapy. Suboptimal 25(OH)D₃ levels in the majority of the participants highlight the relevance of monitoring in this vulnerable population.