Central venous catheters (CVCs) have considerably improved the management of patients with hematological malignancies, by facilitating chemotherapy, supportive therapy and blood sampling. ...Complications of insertion of CVCs include mechanical (arterial puncture, pneumothorax), thrombotic and infectious complications. CVC-related thrombosis and infections are frequently occurring complications and may cause significant morbidity in patients with hematological malignancies. CVC-related thrombosis and infections are related and can therefore not be seen as separate entities. The incidence of symptomatic CVC-related thrombosis had been reported to vary between 1.2 and 13.0% of patients with hematological malignancy. The incidence of CVC-related bloodstream infections varies between 0.0 and 20.8%. There is need for a specific approach regarding diagnosis and treatment of CVC-related thrombosis and infection with specific attention to the preservation of the catheter. Since data on CVC-related infections and thrombosis in hematological patients have been obtained mainly from retrospective studies of small sample size, prospective, randomized studies of prophylactic measures concerning CVC-related thrombosis and infection are warranted.
Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus and all cause mortality. Long-term survivors of ...hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31-49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal of reviewing literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.
Summary
Background
An unmet need remains for improved management in perianal fistulising Crohn's disease (pCD). Recently, local administration of adipose‐derived cells has shown promising results.
...Aims
To assess the safety and feasibility of injection of stromal vascular fraction (SVF) with platelet‐rich plasma (PRP) in patients with pCD.
Methods
Patients ≥ 18 years with pCD were included and underwent fistula curettage, SVF with PRP injection, and closure of the internal opening. The primary endpoint was safety at 12 months. The secondary outcomes were complete radiological healing at 3 months (absence of fluid‐containing tracts on MRI) and partial and complete clinical response at 3 and 12 months (closure of ≥1, respectively, all treated external opening(s)).
Results
Twenty‐five patients were included (35 IQR 25–40 years; 14 56% female); median CD duration 4 IQR 2–8 years. Twenty‐four (95%) patients had previously undergone fistula surgery. No adverse events were encountered at lipoharvesting sites. Two (8%) patients were readmitted to hospital and six (24%) underwent unplanned re‐interventions. Post‐operative MRI (n = 24) showed complete radiological healing in nine (37.5%) patients. Partial clinical response was present in 48% (12/25) at 3 months and in 68% (17/25) at 12 months, and complete clinical closure in five (20%) patients at 3 months and in 10 (40%) patients at 12 months.
Conclusion
Injection with autologous SVF with PRP is feasible and safe in patients with treatment‐refractory pCD. Early complete radiological healing was observed in more than one‐third of patients, and clinical response in two‐thirds of patients at 12 months.
Stromal vascular fraction with platelet‐rich plasma injection during surgery is feasible and safe in treatment‐refractory perianal fistulising Crohn's disease.
Background: The purpose of this study was to determine the prevalence of fatigue and the course of fatigue as a function of chemotherapy in breast cancer patients undergoing adjuvant chemotherapy. ...Patients and methods: In a prospective cohort study, a sample of 157 patients with breast cancer were interviewed, using the Rotterdam Symptom Checklist and the Multidimensional Fatigue Inventory, at the first, third and fifth cycle of adjuvant chemotherapy, as well as 4 and 12 weeks after the last cycle of adjuvant chemotherapy. Patients were treated with either a doxorubicin-containing schedule, or cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Results: The courses of general and physical fatigue are to a large extent similar. After the last cycle of chemotherapy, the CMF group reported a significant increase in fatigue, which was followed by a significant reduction. In the doxorubicin group a significant increase in fatigue was only seen during the first cycles of chemotherapy. The fatigue experienced at the first and the last measurements do not differ significantly. Conclusions: The prevalence of fatigue increased significantly after the start of chemotherapy. After chemotherapy treatment the prevalence rate seemed to decline. A different impact of chemotherapy on the course of fatigue was found. In the doxorubicin group a direct increase in fatigue was found. In the CMF group a moderate direct increase occurred, followed by a delayed strong increase. An increase in fatigue was associated with a decrease in daily functioning. At all measurement occasions fatigue was affected by type of operation, such that women with a mastectomy were more fatigued than women that underwent a lumpectomy. Receiving radiotherapy also led to an increase in fatigue. With this knowledge breast cancer patients can be better informed about what they can expect. Further research should include interventions addressing how to reduce or cope with fatigue during as well as after receiving adjuvant chemotherapy.
Purpose
The aims were to evaluate the construct validity and reliability of the Dutch version of the pediatric-modified Total Neuropathy Score (ped-mTNS) for assessing vincristine-induced peripheral ...neuropathy (VIPN) in Dutch pediatric oncology patients aged 5–18 years.
Methods
Construct validity (primary aim) of the ped-mTNS was determined by testing hypotheses about expected correlation between scores of the ped-mTNS (range: 0–32) and the Common Terminology Criteria for Adverse Events (CTCAE) (range: 0–18) for patients and healthy controls and by comparing patients and controls regarding their total ped-mTNS scores and the proportion of children identified with VIPN. Inter-rater and intra-rater reliability and measurement error (secondary aims) were assessed in a subgroup of study participants.
Results
Among the 112 children (56 patients and 56 age- and gender-matched healthy controls) evaluated, correlation between CTCAE and ped-mTNS scores was as expected (moderate (
r
= 0.60)). Moreover, as expected, patients had significantly higher ped-mTNS scores and more frequent symptoms of VIPN compared with controls (both
p
< .001). Reliability as measured within the intra-rater group (
n
= 10) (intra-class correlation coefficient (ICC
agreement
) = 0.64, standard error of measurement (SEM
agreement
) = 2.92, and smallest detectable change (SDC
agreement
) = 8.1) and within the inter-rater subgroup (
n
= 10) (ICC
agreement
= 0.63, SEM
agreement
= 3.7, and SDC
agreement
= 10.26) indicates insufficient reliability.
Conclusion
The Dutch version of the ped-mTNS appears to have good construct validity for assessing VIPN in a Dutch pediatric oncology population, whereas reliability appears to be insufficient and measurement error high. To improve standardization of VIPN assessment in children, future research aimed at evaluating and further optimizing the psychometric characteristics of the ped-mTNS is needed.
Apple (Malus×domesticaBorkh) is among the main sources of phenolic compounds in the human diet. The genetic basis of the quantitative variations of these potentially beneficial phenolic compounds was ...investigated. A segregating F₁ population was used to map metabolite quantitative trait loci (mQTLs). Untargeted metabolic profiling of peel and flesh tissues of ripe fruits was performed using liquid chromatography–mass spectrometry (LC-MS), resulting in the detection of 418 metabolites in peel and 254 in flesh. In mQTL mapping using MetaNetwork, 669 significant mQTLs were detected: 488 in the peel and 181 in the flesh. Four linkage groups (LGs), LG1, LG8, LG13, and LG16, were found to contain mQTL hotspots, mainly regulating metabolites that belong to the phenylpropanoid pathway. The genetics of annotated metabolites was studied in more detail using MapQTL®. A number of quercetin conjugates had mQTLs on LG1 or LG13. The most important mQTL hotspot with the largest number of metabolites was detected on LG16: mQTLs for 33 peel-related and 17 flesh-related phenolic compounds. Structural genes involved in the phenylpropanoid biosynthetic pathway were located, using the apple genome sequence. The structural geneleucoanthocyanidin reductase(LAR1) was in the mQTL hotspot on LG16, as were seven transcription factor genes. The authors believe that this is the first time that a QTL analysis was performed on such a high number of metabolites in an outbreeding plant species.
•Early-onset cataract is underrecognized as first manifestation of DM1.•Diagnostic delay is common and may have severe medical and emotional consequences.•Patients ask for more attention for the ...psychosocial consequences of a diagnostic delay.•Ophthalmologists can play a crucial role in the early diagnosis of DM1.
Myotonic dystrophy type 1 is a neuromuscular disorder affecting multiple organ systems and is characterized by a variety of clinical presentations. Anticipation leads to an earlier and more severe phenotype in subsequent generations. Early-onset cataract is a common initial manifestation of the late or adult-onset type of myotonic dystrophy 1. Due to its multicausal nature, early-onset cataract is often not recognized as a feature of this disease, leading to diagnostic delay resulting in consequences for successive generations, treatment and counseling. A qualitative study with semi-structured interviews was performed with purposive sampling of eight participants with myotonic dystrophy type 1 and early-onset cataract to investigate the physical and psychosocial consequences experienced due to diagnostic delay. Prior to the early-onset cataract, all participants experienced other multisystem symptoms that could have been explained by myotonic dystrophy. The diagnostic delay had severe hereditary consequences: a subsequent generation with more severely affected (grand)children was born resulting in large emotional burden for the patients. To conclude, early-onset cataract is a warning sign and ophthalmologists play a crucial role in the early detection of myotonic dystrophy type 1 by recognizing this symptom and preventing the birth of severely affected children leading to emotional and psychosocial consequences.
OBJECTIVES:A growing body of evidence suggests that age affects the main pathophysiologic mechanisms of the acute respiratory distress syndrome. This may imply the need for developing age-tailored ...therapies for acute respiratory distress syndrome. However, underlying molecular mechanisms governing age-related susceptibility first need to be unraveled. In a rat model of acute lung injury, we investigated whether age affects the balance between the two key enzymes of the pulmonary renin-angiotensin system, angiotensin-converting enzyme, and angiotensin-converting enzyme 2. We hypothesized that aging shifts the balance toward the lung injury–promoting angiotensin-converting enzyme, which may form an explanation for the differences in severity of lung injury between different age groups.
DESIGN:Prospective, randomized controlled animal study.
SETTING:University medical research laboratory.
SUBJECTS:Infant (15 ± 2 d), juvenile (37 ± 2 d), adult (4 ± 0.2 mo), and elderly (19.5 ± 0.5 mo) male RCCHan Wistar rats.
INTERVENTIONS:Lung injury was induced by intratracheal administration of lipopolysaccharide (5 mg/kg) and 4 hours of mechanical ventilation (15 mL/kg).
MEASUREMENTS AND MAIN RESULTS:In lipopolysaccharide-exposed and mechanical ventilated rats, angiotensin-converting enzyme activity in bronchoalveolar lavage fluid increased 3.2-fold in elderly when compared with infants. No changes in bronchoalveolar lavage fluid angiotensin-converting enzyme 2 activity were found. In addition, membrane-bound angiotensin-converting enzyme activity decreased. Together with the presence of angiotensin-converting enzyme-sheddase ADAM9 (a disintegrin and metalloproteinase domain–containing protein 9) and an age-dependent increase in tumor necrosis factor-α, an activator of ADAM9, these results indicate increased shedding of angiotensin-converting enzyme in the alveolar compartment, thereby shifting the balance toward the injurious pathway. This imbalance was associated with an increased inflammatory mediator response and more lung injury (wet-to-dry ratio and histology) in elderly rats.
CONCLUSIONS:Increasing age is associated with an imbalance of the pulmonary renin-angiotensin system, which correlates with aggravated inflammation and more lung injury. These changes might form the ground for new therapeutic strategies in terms of dosing and effectiveness of renin-angiotensin system–modulating agents for treatment of acute respiratory distress syndrome.
Grade 3 follicular lymphoma (FL) has aggressive clinical behavior. To evaluate the optimal first transplantation approach in relapsed/refractory grade 3 FL patients, we compared the long-term ...outcomes after allogeneic (allo-) vs autologous hematopoietic cell transplantation (auto-HCT) in the rituximab era. A total of 197 patients undergoing first reduced-intensity conditioning (RIC) allo-HCT or first auto-HCT during 2000-2012 were included. Rituximab-naive patients were excluded. Allo-HCT recipients were younger, more heavily pretreated and had a longer interval between diagnosis and HCT. The 5-year probabilities of non-relapse mortality (NRM), relapse/progression, PFS and overall survival (OS) for auto-HCT vs allo-HCT groups were 4% vs 27% (P<0.001), 61% vs 20% (P<0.001), 36% vs 51% (P=0.07) and 59% vs 54% (P=0.7), respectively. On multivariate analysis, auto-HCT was associated with reduced risk of NRM (relative risk (RR)=0.20; P=0.001). Within the first 11 months post HCT, auto- and allo-HCT had similar risks of relapse/progression and PFS. Beyond 11 months, auto-HCT was associated with higher risk of relapse/progression (RR=21.3; P=0.003) and inferior PFS (RR=3.2; P=0.005). In the first 24 months post HCT, auto-HCT was associated with improved OS (RR=0.42; P=0.005), but in long-time survivors (beyond 24 months) it was associated with inferior OS (RR=3.6; P=0.04). RIC allo-HCT as the first transplant approach can provide improved PFS and OS, in long-term survivors.
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