Deferring diagnostic evaluation of suspected deep vein thrombosis using direct oral anticoagulant or low-molecular-weight heparin as a single dose anticoagulant: A prospective real-world study in a regionwide care pathway.

BACKGROUND: Patients with suspected deep vein thrombosis (DVT) are typically referred to the emergency department for immediate evaluation. To enhance efficiency, our hospital implemented a regional, general practitioner (GP)-driven DVT care pathway, deferring diagnostic evaluation to a scheduled outpatient DVT clinic appointment the following day. Patients receive a single dose anticoagulant from their GP to prevent thrombosis progression while awaiting diagnostic workup. This prospective study aimed to evaluate the safety and patient preferences regarding the DVT care pathway and the type of single dose anticoagulant (low-molecular-weight heparin (LMWH) vs. direct oral anticoagulant (DOAC)). METHODS: Patients enrolled in the DVT care pathway between June 2021 and July 2023 were eligible. Until July 2022, LMWH was administered, and thereafter, the protocol recommended DOAC as the single dose anticoagulant. Patients completed questionnaires, incorporating patient-reported outcome and experience measures (PROMs/PREMs), during their DVT clinic visit and after five days. The primary endpoint was bleeding events within 72 h of receiving the single dose anticoagulant. RESULTS: Of 460 included patients, 229 received LMWH and 231 received DOAC as the single dose anticoagulant. DVT was confirmed in 24.8 % of patients. No major or clinically relevant non-major bleeding were reported. LMWH was associated with more minor bleedings (22.3 % vs. DOAC 13.4 %), primarily attributed to injection site hematomas. Patients reported high satisfaction with the DVT care pathway (96.5 %) and generally preferred DOAC over LMWH. CONCLUSION: Deferring diagnostic evaluation for DVT using a single dose of either LMWH or DOAC in a real-world population is deemed safe. Considering practical advantages, patient preferences, and fewer skin hematomas, we favor DOACs as the single dose anticoagulant in this care pathway.

Deferring diagnostic evaluation for suspected deep venous thrombosis using a single dose of anticoagulant: Real-world data from a regionwide care pathway.

BACKGROUND: Patients with suspected deep venous thrombosis (DVT) are typically referred to the emergency department (ED) for immediate evaluation. However, this often contributes to ED overcrowding and necessitates round-the-clock sonographic examinations. Therefore, we implemented a regionwide care pathway for deferring diagnostic workup of suspected DVT until the following day. Patients receive a single anticoagulant dose from their general practitioner (GP) to prevent progression of DVT in the interval between referral and diagnostic evaluation. The next day, patients undergo comprehensive evaluation at our outpatient DVT clinic, including venous ultrasound. This retrospective study aims to provide real-world data on the safety of this care pathway regarding the occurrence of bleeding complications and pulmonary embolism (PE). METHODS: We included all GP-referred patients with suspected DVT in 2018 and 2019. Patients with absolute contraindications to deferred evaluation or anticoagulation were excluded. The primary endpoint was the occurrence of bleeding complications. Secondary endpoints included PE events and all-cause mortality within seven days following DVT evaluation. RESULTS: Among 1,024 included patients, DVT was confirmed in 238 patients (23.2%) and superficial thrombophlebitis in 98 patients (9.6%). No bleeding events were recorded in patients in whom DVT was ruled out. PE was confirmed in eight patients on the same day as DVT evaluation (0.8%, 95%CI 0.4-1.6) and in six patients within seven days following DVT evaluation (0.6%, 0.2-1.3%). No deaths occurred during this timeframe. CONCLUSION: This real-world study observed a very low incidence of bleeding complications and PE events, indicating that this care pathway of deferred DVT workup is safe and may offer a more streamlined diagnostic approach for patients with suspected DVT.

Survey of Challenges, Goals, and Interventions for Patients With Lymphoma During Aftercare Consultation: An Exploratory Cross-Sectional Study.

This study described the challenges, personal goals, and interventions of patients with lymphoma in various domains of life that emerged from an aftercare consultation based on shared decision-making principles with a nurse practitioner. A cross-sectional exploratory design was used with a sample of 49 patients. Challenges, goals, and interventions were measured based on 4 domains of life: "my health," "my activities," "my environment" and "my own way." Most challenges were experienced in the domain of "my health," which included a loss of physical condition, reduced muscle strength, and fatigue. Patients set personal goals related to the experienced challenges, such as restoring physical condition to prediagnosis levels. Accordingly, 45 patients (84%) chose an intervention to improve physical condition and muscle strength and 33 patients (67%) chose to be referred to specialized care.

Clinical impact of assessing thrombus age using magnetic resonance venography prior to catheter-directed thrombolysis.

OBJECTIVES: Magnetic resonance venography (MRV) is underutilized in the evaluation of thrombus properties prior to endovascular treatment but may improve procedural outcomes. We therefore investigated the clinical impact of using a dedicated MRV scoring system to assess thrombus characteristics prior to endovascular intervention for iliofemoral deep vein thrombosis (DVT). METHODS: This is a post hoc analysis of data from the CAVA trial ( Clinicaltrials.gov :NCT00970619). MRV studies of patients receiving ultrasound-accelerated catheter-directed thrombolysis (CDT) for iliofemoral DVT were reviewed. Thrombus age-related imaging characteristics were scored and translated into an overall score (acute, subacute, or old). MRV scores were compared to patient-reported complaints. MRV-scored groups were compared for CDT duration and success rate. RESULTS: Fifty-six patients (29 men; age 50.8 ± 16.4 years) were included. Using MRV, 27 thrombi were classified acute, 17 subacute, and 12 old. Based on patient-reported complaints, 11 (91.7%) of these old thrombi would have been categorized acute or subacute, and one (3.7%) of the acute thrombi as old. Average duration of CDT to > 90% restored patency differed significantly between groups (p < 0.0001): average duration was 23 h for acute thromboses (range: 19-25), 43 h for subacute (range: 41-62), and 85 h for old thromboses (range: 74-96). CDT was almost eleven times more successful in thromboses characterized as acute and subacute compared to old thromboses (OR: 10.7; 95% CI 2.1-55.5). CONCLUSION: A dedicated MRV scoring system can safely discriminate between acute, subacute, and old thromboses. MRV-based selection is predictive of procedural duration and success rate and can help avoid unnecessary complications. KEY POINTS: • Thrombus age, characterized by MRV as acute, subacute, and old, can predict CDT duration and probability of success. • Accurate pre-interventional MRV-based thrombus aging has the potential to facilitate identification of eligible patients and may thus prevent CDT-related complications.

CAVA (Ultrasound-Accelerated Catheter-Directed Thrombolysis on Preventing Post-Thrombotic Syndrome) Trial: Long-Term Follow-Up Results.

Background The CAVA (Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome) trial did not show a reduction of post-thrombotic syndrome (PTS) after additional ultrasound-accelerated catheter-directed thrombolysis in patients with acute iliofemoral deep vein thrombosis at 1-year follow-up. This prespecified analysis of the CAVA trial aimed to determine the impact of additional thrombolysis on outcomes of PTS at long-term follow-up. Methods and Results Patients aged 18 to 85 years with a first-time acute iliofemoral deep vein thrombosis were included and randomly assigned (1:1) to either standard treatment plus ultrasound-accelerated catheter-directed thrombolysis or standard treatment alone. The primary outcome was the proportion of PTS (Villalta score ≥5 on 2 occasions ≥3 months apart or venous ulceration) at the final follow-up visit. Additionally, PTS according to the International Society on Thrombosis and Haemostasis (ISTH) consensus definition was assessed to allow external comparability. Major bleedings were the main safety outcome. At a median follow-up of 39.0 months (interquartile range, 23.3-63.8), 120 patients (79.8%) participated in the final follow-up visit: 62 from the intervention group and 58 from the standard treatment group. PTS developed in 19 (30.6%) versus 26 (44.8%) patients, respectively (odds ratio [OR], 0.54; 95% CI, 0.26 to 1.15 [P=0.11]), with an absolute difference between groups of -14.2% (95% CI, -32.0% to 4.8%). Using the ISTH consensus definition, a significant reduction in PTS was observed (29 [46.8%] versus 40 [69.0%]) (OR, 0.40; 95% CI, 0.19-0.84 [P=0.01]) with an absolute difference between groups of -22.2% (95% CI, -39.8% to -2.8%). No new major bleedings occurred following the 12-month follow-up. Conclusions The impact of additional ultrasound-accelerated catheter-directed thrombolysis on the prevention of PTS was found to increase with time. Although this study was limited by its sample size, the overall findings indicate a reduction of mild PTS without impact on quality of life. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00970619.

Stories of Lymphoma Survivors in Early Aftercare: A Narrative Inquiry.

BACKGROUND: Survivors of lymphoma experience multiple challenges after treatment. However, a lack of knowledge of in-depth experiences of lymphoma survivors in early aftercare persists. OBJECTIVE: To gain an in-depth understanding of the experiences of lymphoma survivors in early aftercare who have received an aftercare consultation based on evidence-based guideline recommendations, with an advanced practice nurse. METHODS: This study used a narrative design. We recruited lymphoma survivors after a best-practice aftercare consultation with an advanced practice nurse. A total of 22 lymphoma survivors and 9 partners participated. Data were collected through narrative interviews and analyzed according to thematic narrative analysis. RESULTS: Six themes emerged: living and dealing with health consequences, coping with work and financial challenges, having a positive outlook and dealing with uncertainty, deriving strength from and experiencing tensions in relationships, getting through tough times in life, and receiving support from healthcare professionals. CONCLUSIONS: The stories of lymphoma survivors in early aftercare revealed their experiences of how they coped with a range of challenges in their personal lives. Choosing an aftercare trajectory based on an aftercare consultation that encourages patients to think about their issues, goals, and possible aftercare options may be useful for their transition from treatment to survivorship. IMPLICATIONS FOR PRACTICE: Survivors' social support and self-management capabilities are important aspects to be addressed in cancer care. An aftercare consultation involving shared goal setting and care planning may help nurses provide personalized aftercare.

Rituximab-CHOP With Early Rituximab Intensification for Diffuse Large B-Cell Lymphoma: A Randomized Phase III Trial of the HOVON and the Nordic Lymphoma Group (HOVON-84).

PURPOSE: Immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become standard of care for patients with diffuse large B-cell lymphoma (DLBCL). This randomized trial assessed whether rituximab intensification during the first 4 cycles of R-CHOP could improve the outcome of these patients compared with standard R-CHOP. PATIENTS AND METHODS: A total of 574 patients with DLBCL age 18 to 80 years were randomly assigned to induction therapy with 6 or 8 cycles of R-CHOP-14 with (RR-CHOP-14) or without (R-CHOP-14) intensification of rituximab in the first 4 cycles. The primary end point was complete remission (CR) on induction. Analyses were performed by intention to treat. RESULTS: CR was achieved in 254 (89%) of 286 patients in the R-CHOP-14 arm and 249 (86%) of 288 patients in the RR-CHOP-14 arm (hazard ratio [HR], 0.82; 95% CI, 0.50 to 1.36; P = .44). After a median follow-up of 92 months (range, 1-131 months), 3-year failure-free survival was 74% (95% CI, 68% to 78%) in the R-CHOP-14 arm versus 69% (95% CI, 63% to 74%) in the RR-CHOP-14 arm (HR, 1.26; 95% CI, 0.98 to 1.61; P = .07). Progression-free survival at 3 years was 74% (95% CI, 69% to 79%) in the R-CHOP-14 arm versus 71% (95% CI, 66% to 76%) in the RR-CHOP-14 arm (HR, 1.20; 95% CI, 0.94 to 1.55; P = .15). Overall survival at 3 years was 81% (95% CI, 76% to 85%) in the R-CHOP-14 arm versus 76% (95% CI, 70% to 80%) in the RR-CHOP-14 arm (HR, 1.27; 95% CI, 0.97 to 1.67; P = .09). Patients between ages 66 and 80 years experienced significantly more toxicity during the first 4 cycles in the RR-CHOP-14 arm, especially neutropenia and infections. CONCLUSION: Early rituximab intensification during R-CHOP-14 does not improve outcome in patients with untreated DLBCL.

Association of Successful Ultrasound-Accelerated Catheter-Directed Thrombolysis with Postthrombotic Syndrome: A Post Hoc Analysis of the CAVA Trial.

BACKGROUND: The CAVA trial did not show the anticipated risk reduction for postthrombotic syndrome (PTS) after thrombus removal via additional ultrasound-accelerated catheter-directed thrombolysis (UACDT) in patients with acute iliofemoral deep vein thrombosis (IFDVT). Difficulties in achieving an effective degree of recanalization through thrombolysis may have influenced outcomes. We therefore assessed whether successful UACDT (restored patency ≥ 90%) did reduce the development of PTS. METHODS: This CAVA trial post hoc analysis compared the proportion of PTS at 1-year follow-up between patients with successful UACDT and patients that received standard treatment only. In addition, clinical impact as well as determinants of successful thrombolysis were explored. RESULTS: UACDT was initiated in 77 (50.7%) patients and considered successful in 41 (53.2%, interrater agreement κ = 0.7, 95% confidence interval 0.47-0.83). PTS developed in 15/41 (36.6%) patients in the successful UACDT group versus 33/75 (44.0%) controls (p = 0.44). In this comparison, successful UACDT was associated with lower Venous Clinical Severity Score (3.50 ± 2.57 vs. 4.82 ± 2.74, p = 0.02) and higher EuroQOL-5D (EQ-5D) scores (40.2 ± 36.4 vs. 23.4 ± 34.4, p = 0.01). Compared with unsuccessful UACDT, successful UACDT was associated with a shorter symptom duration at inclusion (p = 0.05), and higher rates of performed adjunctive procedures (p < 0.001) and stent placement (p < 0.001). CONCLUSION: Successful UACDT was not associated with a reduced proportion of PTS 1 year after acute IFDVT compared with patients receiving standard treatment alone. There was, however, a significant reduction in symptom severity and improvement of generic quality of life according to the EQ-5D. Better patient selection and optimization of treatment protocols are needed to assess the full potential of UACDT for the prevention of PTS. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT00970619.

Ultrasound-accelerated catheter-directed thrombolysis versus anticoagulation for the prevention of post-thrombotic syndrome (CAVA): a single-blind, multicentre, randomised trial.

BACKGROUND: Early thrombus removal might prevent post-thrombotic syndrome by preserving venous function and restoring flow. Previous trials comparing additional catheter-directed thrombolysis to standard treatment showed conflicting outcomes. We aimed to assess the benefit of additional ultrasound-accelerated catheter-directed thrombolysis for the prevention of post-thrombotic syndrome compared with standard therapy in patients with iliofemoral deep-vein thrombosis. METHODS: We did a multicentre, randomised, single-blind, allocation-concealed, parallel group, superiority trial in 15 hospitals in the Netherlands. Patients aged 18-85 years with a first-time acute iliofemoral deep-vein thrombosis and symptoms for no more than 14 days were randomly assigned (1:1) to either standard treatment with additional ultrasound-accelerated catheter-directed thrombolysis or standard treatment alone. Randomisation was done with a web-based automatic programme and a random varying block size (2-12), stratified by age and centre. Standard treatment included anticoagulant therapy, compression therapy (knee-high elastic compression stockings; 30-40 mmHg), and early ambulation. Additional ultrasound-accelerated catheter-directed thrombolysis was done with urokinase with a starting bolus of 250 000 international units (IU) in 10 mL NaCl followed by a continuous dose of 100 000 IU/h for a maximum of 96 h through the Ekos Endowave-system. Adjunctive percutaneous transluminal angioplasty, thrombosuction, or stenting was performed at the discretion of the physician who performed the intervention. The primary outcome was the proportion of patients with post-thrombotic syndrome at 12 months diagnosed according to the original Villalta criteria-a Villalta-score of at least 5 on two consecutive occasions at least 3 months apart or the occurrence of venous ulceration-and was assessed in a modified intention-to-treat population of all randomly assigned patients who passed screening and started treatment. The safety analysis was assessed in the same modified intention-to-treat population. This study is complete and is registered at ClinicalTrials.gov, NCT00970619. FINDINGS: Between May 28, 2010, and Sept 18, 2017, 184 patients were randomly assigned to either additional ultrasound-accelerated catheter-directed thrombolysis (n=91) or standard treatment alone (n=93). Exclusion because of screening failure or early withdrawal of informed consent resulted in 77 patients in the intervention group and 75 in the standard treatment group starting allocated treatment. Median follow-up was 12·0 months (IQR 6·0-12·0). 12-month post-thrombotic syndrome occurred in 22 (29%) patients allocated to additional treatment versus 26 (35%) patients receiving standard treatment alone (odds ratio 0·75 [95% CI 0·38 to 1·50]; p=0·42). Major bleeding occurred in four (5%) patients in the intervention group, with associated neuropraxia or the peroneal nerve in one patient, and no events in the standard treatment group. No serious adverse events occurred. None of the four deaths (one [1%] in the intervention group vs three [4%] in the standard treatment group) were treatment related. INTERPRETATION: This study showed that additional ultrasound-accelerated catheter-directed thrombolysis does not change the risk of post-thrombotic syndrome 1 year after acute iliofemoral deep-vein thrombosis compared with standard therapy alone. Although this trial is inconclusive, the outcome suggests the possibility of a moderate beneficial effect with additional ultrasound-accelerated catheter-directed thrombolysis. Further research is therefore warranted to better understand this outcome in the context of previous trials, preferably by combining the available evidence in an individual patient data meta-analysis. FUNDING: The Netherlands Organisation for Health Research and Development (ZonMw), Maastricht University Medical Centre, BTG-Interventional Medicine.

Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial.

BACKGROUND: In patients with recently diagnosed multiple myeloma, the HOVON-50 phase 3 trial showed improved event-free survival for thalidomide-containing induction and maintenance regimens (in conjunction with high-dose melphalan and autologous stem cell transplantation [auto-SCT]) after a median of 52 months of follow-up, by comparison with regimens containing classical cytotoxic drugs. In this follow-up analysis, we aimed to determine the long-term effects of thalidomide in induction and maintenance therapy in multiple myeloma. METHODS: In this open-label, phase 3 randomised controlled trial, patients with recently diagnosed multiple myeloma were recruited from 44 Dutch and Belgian hospitals. Participants had been diagnosed with multiple myeloma of Durie-Salmon stage II or III and were aged 18-65 years. Patients were randomly assigned (1:1) either to receive three 28-day cycles of vincristine (0·4 mg, intravenous rapid infusion on days 1-4), doxorubicin (9 mg/m2, intravenous rapid infusion on days 1-4) and dexamethasone (40 mg, orally on days 1-4, 9-12, and 17-20; control group); or to receive the same regimen, but with thalidomide (200-400 mg, orally on days 1-28) instead of vincristine (thalidomide group). No masking after assignment to intervention was used. Patients were randomly assigned to groups, stratified by centre and treatment policy (one vs two courses of high-dose melphalan and auto-SCT). After stem cell harvest, patients received one or two courses of 200 mg/m2 melphalan intravenously with auto-SCT. Patients with at least a partial response to high-dose melphalan and auto-SCT were eligible for maintenance therapy, starting 2-3 months after high-dose melphalan. Patients in the control group received maintenance therapy with interferon alfa (3 ×  106 international units, subcutaneously, three times weekly). Patients in the thalidomide group received thalidomide as maintenance therapy (50 mg, orally, daily). Maintenance therapy was given until relapse, progression, or the occurrence of adverse events. The primary endpoint of the study was event-free survival (EFSc; censored at allogeneic stem cell transplantation), analysed by intention to treat. The study is closed for enrolment and this Article represents the final analysis. This trial was registered with the Netherlands Trial Register, number NTR238. FINDINGS: Between Nov 27, 2001 and May 31, 2005, 556 patients were enrolled in the study, of whom 536 (96%) were eligible for evaluation and were randomly allocated (268 [50%] to the control group and 268 [50%] to the thalidomide group). These 536 patients were assessed for the primary endpoint of EFSc. At an extended median follow-up of 129 months (IQR 123-136), EFSc was significantly longer in the thalidomide group compared with the control group (multivariate analysis hazard ratio [HR] 0·62, 95% CI 0·50-0·77; p<0·0001). Thalidomide maintenance was stopped because of toxicity in 65 (42%) of 155 patients in the thalidomide group (neuropathy in 49 [75%] patients, skin reactions in four [6%] patients, fatigue in two [3%] patients, and as other symptoms [such as abdominal pain, pancreatitis, and dyspnoea] in ten [15%] patients). 24 (27%) of 90 patients in the control group discontinued protocol treatment during maintenance therapy with interferon alfa because of toxicity (five [21%] patients with psychiatric side-effects, five [21%] patients with flu-like symptoms, four [17%] patients with haematological toxicity [thrombocytopenia and leucocytopenia], three [13%] patients with skin reactions, and seven [29%] patients with other symptoms [such as infections, cardiomyopathy, and headache]). The frequency of second primary malignancies was similar in both groups. There were 23 second primary malignancies in 17 patients in the control group and 29 second primary malignancies in 24 patients in the thalidomide group. There were 19 treatment-related deaths in the control group, and 16 treatment-related deaths in the thalidomide group. INTERPRETATION: Our data indicate that thalidomide-based treatment could be a treatment option for patients with multiple myeloma who are eligible for auto-SCT who live in countries without access to proteasome inhibitors or lenalidomide. However, careful follow-up and timely dose adjustments are important to prevent the development of thalidomide-induced neurotoxicity. FUNDING: The Dutch Cancer Foundation.

A conversation approach based on shared goal-setting and shared decision-making for nurses in cancer aftercare: A developmental study.

PURPOSE: This study aimed to develop and pretest a systematic conversation approach for nurses to tailor aftercare to oncology patient's goals, unmet needs and wishes. METHODS: We used an iterative developmental process for complex interventions: 1. Identifying problems 2. Identifying overall objectives 3. Designing the intervention 4. Pretesting and adapting the intervention. RESULTS: The main results of the problem identification were: non-systematic and incomplete screening of potential issues, caveats in providing information, and shared decision-making. The overall objective formulated was: To develop a model for aftercare conversations based on shared goal-setting and decision-making. The conversation approach consists of four phases: 1. Preparation of the consultation including a questionnaire, 2. Shared goal-setting by means of a tool visualizing domains of life, and 3. Shared care planning by means of an overview of possible choices in aftercare, a database with health care professionals and a cancer survivorship care plan. 4. EVALUATION: The results of the pretest revealed that the conversation approach needs to be flexible and tailored to the patient and practice setting, and embedded in the care processes. The conversation approach was perceived as enhancing patient-centeredness and leading to more in-depth consultations. CONCLUSION: The conversation approach was developed in co-creation with stakeholders. The results of the pretest revealed important implications and suggestions for implementation in routine care. The aftercare conversation approach can be used by nurses to provide tailored patient-centered evidence-based aftercare. Tailored aftercare should support oncology patient's goals, unmet needs and wishes. Further tailoring is needed.

Intermediate and nonclassical monocytes show heterogeneity in patients with different types of acute coronary syndrome.

This study was performed to gain further insight in the heterogeneity of monocytes in the different categories of acute coronary syndrome (ACS), especially between patients with unstable angina pectoris, ST-elevation myocardial infarction (STEMI), and non-ST-elevation myocardial infarction (NSTEMI). For this purpose, blood samples were collected in the acute phase from patients presenting with an ACS. These samples were examined with multiparameter flow cytometry to identify the different monocyte subsets and to analyze the expression of monocyte-associated molecules. Leukocytes, as well as an absolute number of monocytes, showed a clear and significant increase in patients with STEMI. This increase was seen in all subtypes of monocytes. The classical monocytes (CD14++CD16-) of patients with an NSTEMI had a significantly increased CD11b expression when compared to the control group, while these cells showed a decreased expression pattern in STEMI patients. This increased CD11b-expression was also seen in the intermediate monocytes of NSTEMI, while it was almost completely downregulated on the intermediate monocytes of STEMI. Finally, CX3CR1, which is almost exclusively expressed on intermediate and nonclassical monocytes, showed a significant decrease in expression in patients with STEMI. In conclusion, intermediate and nonclassical monocytes have a different immunophenotypic pattern in patients with STEMI versus NSTEMI. These differences reflect the pro-inflammatory state of the monocytes in NSTEMI and can be used as target molecules for novel therapeutic strategies to diminish the migration of proinflammatory monocytes into the myocardial tissue. © 2017 International Society for Advancement of Cytometry.

The pro- and anticoagulant role of blood-borne phagocytes in patients with acute coronary syndrome.

This study was performed to gain further insight in pro- and anticoagulant characteristics of leukocytes in acute coronary syndrome (ACS). For this purpose, patients presenting on the emergency department (ED) with anginal chest pain were included in this study. In peripheral blood, procoagulant tissue factor (TF) expression was measured in the different blood-borne phagocytes, i.e. neutrophilic granulocytes and the three different monocyte subsets based on expression of CD14 and CD16. Simultaneously, intracellular presence of platelet-(CD41) and/or endothelial cell-remnants (CD62e) was analysed in these different leukocyte subsets. Neutrophils showed a weak intracellular staining of CD62e and CD41 that increased with severity of ACS. Monocytes, and especially the classical (CD14++CD16-) and intermediate monocytes (CD14++CD16+) showed a clear and significant increase in intracellular CD41-staining after coronary damage. The different monocyte subsets showed an increase in expression of TF in severe ACS. Finally, it appeared that also neutrophils showed a significant increase in expression of TF on their membrane. In conclusion, this study showed an increased intracellular staining in blood-borne phagocytes for CD62e and CD41 in patients with ACS compared to non-cardiac related control patients. This indicates that at least in the acute phase of ACS phagocytosis of platelet and endothelial cell-remnants is increased. These data support the recent hypothesis that neutrophils protect against further thrombotic processes by clearing platelet and endothelial cell-remnants. In addition, this study shows that the different monocyte subsets are also involved in this process. Furthermore, both monocytes and neutrophils show increased TF expression in ACS.

Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme.

The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors for response, we analysed a cohort of 90 MDS, CMML and AML patients who have been treated in a Dutch compassionate named patient programme. Patients received azacitidine for a median of five cycles (range 1-19). The overall response rate (complete/partial/haematological improvement) was 57% in low risk MDS, 53% in high risk MDS, 50% in CMML, and 39% in AML patients. Median overall survival (OS) was 13·0 (9·8-16·2) months. Multivariate analysis confirmed circulating blasts [Hazard Ratio (HR) 0·48, 95% confidence interval (CI) 0·24-0·99; P = 0·05] and poor risk cytogenetics (HR 0·45, 95% CI 0·22-0·91; P = 0·03) as independent predictors for OS. Interestingly, this analysis also identified platelet doubling after the first cycle of azacitidine as a simple and independent positive predictor for OS (HR 5·4, 95% CI 0·73-39·9; P = 0·10). In conclusion, routine administration of azacitidine to patients with variable risk groups of MDS, CMML and AML is feasible, and subgroups with distinct efficacy of azacitidine treatment can be identified.

A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma.

The phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and dexamethasone, or to arm B: thalidomide 200 mg orally, days 1 to 28 plus adriamycin and dexamethasone. After induction therapy and stem cell mobilization, patients were to receive high-dose melphalan, 200 mg/m(2), followed by maintenance with alpha-interferon (arm A) or thalidomide 50 mg daily (arm B). Thalidomide significantly improved overall response rate as well as quality of the response before and after high dose melphalan. Best overall response rate on protocol was 88% and 79% (P = .005), at least very good partial remission 66% and 54% (P = .005), and complete remission 31% and 23% (P = .04), respectively, in favor of the thalidomide arm. Thalidomide also significantly improved event-free survival from median 22 months to 34 months (P < .001), and prolonged progression free from median 25 months to 34 months (P < .001). Median survival was longer in the thalidomide arm, 73 versus 60 months; however, this difference was not significant (P = .77). Patients randomized to thalidomide had strongly reduced survival after relapse. This trial was registered on www.controlled-trials.com as ISRCTN06413384.

[Interstitial pneumonitis as an adverse effect of thalidomide]. / Interstitiële pneumonitis als bijwerking van thalidomide.

A 67-year-old man was admitted to the hospital with symptoms of progressive dyspnoea. For 2 months he had received second-line treatment with dexamethasone and thalidomide for a multiple myeloma. Physical examination revealed a tachypnoeic patient and arterial blood gas analysis revealed a respiratory alkalosis and severe hypoxaemia. A high-resolution CT scan showed diffuse ground glass opacities in both lungs. Pulmonary function testing indicated severe diffusion capacity impairment. Bronchoalveolar lavage and cultures excluded the possibility of an infectious agent. The thalidomide treatment was discontinued whereupon the hypoxaemia and the ground glass opacities resolved and the diffusion capacity impairment improved. When a patient treated with thalidomide presents with dyspnoea and hypoxaemia with ground glass opacities, thalidomide-induced pneumonitis should be considered. Withdrawing thalidomide is the only treatment.

Risks and benefits of transcatheter thrombolytic therapy in patients with splanchnic venous thrombosis.

Transcatheter local thrombolytic therapy in patients with acute, extended splanchnic venous thrombosis is controversial. Here we present our single-center experience with transcatheter thrombolytic therapy in these patients. All consecutive patients (n = 12) with acute, extended splanchnic venous thrombosis who underwent transcatheter thrombolytic therapy in our hospital, were included in this study. Thrombolytic therapy was successful for three thrombotic events and partially successful for four thrombotic events. Two patients developed minor procedure-related bleeding (17%). Six patients (50%) developed major procedure-related bleeding, with a fatal outcome in two. Transcatheter thrombolytic therapy in patients with acute, extended splanchnic vein thrombosis is found to be associated with a high rate of procedure-related bleeding. Therefore, thrombolysis should be reserved for patients in whom the venous flow cannot be restored by using conventional anticoagulant therapy or stent placement across the thrombosed vessel segment.