[Palliative care in practice]. / Palliatieve zorg in de praktijk.

In palliative care patient problems often are complex and have elements that relate to more than one dimension and therefore require a multidisciplinary approach.In this article the methodical approach of "palliative reasoning" is described, which helps to analyse, treat and follow up complex patient problems in the palliative phase. Furthermore, tips, general recommendations and treatment options are described based on existing Dutch clinical practice palliative care guidelines, literature and expert opinion.

Muscle mass and strength gains following 6 months of resistance type exercise training are only partly preserved within one year with autonomous exercise continuation in older adults.

INTRODUCTION: Although resistance type exercise training (RT) effectively increases muscle mass and strength in older individuals, it remains unclear whether gains in muscle mass and strength are maintained without continued supervised training. We assessed the capacity of older individuals to maintain muscle mass and strength gains one year after partaking in a successful RT program. METHODS: Fifty-three healthy older adults performed a 24-wk supervised RT program. Upon the cessation of the training program, participants were not provided with any advice or incentives to continue exercise training. One year after completion of the training program, all participants were contacted and invited back to the laboratory to assess anthropometrics, body composition (DXA), quadriceps muscle cross-sectional area (CSA) (CT-scan), muscle strength (1RM knee extension/leg press), and muscle fiber characteristics (muscle biopsy). Following primary analyses on all participants that responded to the invitation (n = 35), participants were divided into two groups: individuals who had continued to perform exercise training on an individual basis (EXER group; n = 16) and individuals who had not continued to perform any regular exercise (STOP group; n = 19) after completing the RT program. RESULTS: The initial increases in quadriceps CSA (+506 ±â€¯209 and +584 ±â€¯287 mm2) and knee extension strength (+32 ±â€¯12 vs +34 ±â€¯10 kg) after the 24-wk RT program did not differ between the STOP and EXER group (all P > 0.05). One year after discontinuation of the RT program, participants had lost muscle mass (P < 0.01), with a greater decline in quadriceps CSA in the STOP vs EXER group (-579 ±â€¯268 vs -309 ±â€¯253 mm2, respectively; P < 0.05). Muscle strength had decreased significantly compared to values after completing the RT program (P < 0.01), with no differences observed between the STOP vs EXER group (knee extension: -21 ±â€¯8 vs -18 ±â€¯8 kg, respectively; P > 0.05), yet remained higher compared with values before the RT program (P < 0.05). CONCLUSION: Though prolonged RT can effectively increase muscle mass and strength in the older population, muscle mass gains are lost and muscle strength gains are only partly preserved within one year if the supervised exercise program is not continued.

Rapid on-site evaluation during endoscopic ultrasound-guided fine-needle aspiration of lymph nodes does not increase diagnostic yield: A randomized, multicenter trial.

OBJECTIVES: Studies on the impact of rapid on-site evaluation (ROSE) during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of lymph nodes are retrospective and have shown conflicting results. We aimed to compare the diagnostic yield of EUS-FNA of lymph nodes with ROSE (ROSE+) and without ROSE (ROSE-). METHODS: This was a multicenter, randomized controlled trial. Consecutive patients who were scheduled to undergo EUS-FNA of mediastinal or abdominal lymph nodes were randomized to ROSE+ or ROSE-. In the ROSE+ group, the number of passes was dictated by the on-site cytotechnician. In the ROSE- group, five passes were performed without interference from the cytotechnician. All samples were reviewed by a single-expert cytopathologist, blinded to group allocation. Primary endpoint was diagnostic yield with and without ROSE. RESULTS: After inclusion of 90 patients, interim analysis showed futility of study continuation since diagnostic yield of ROSE+ and ROSE- were comparable. A total of 91 patients were randomized to ROSE+ (N = 45) or ROSE- (N = 46). Diagnostic yield of ROSE+ and ROSE- and diagnostic accuracy were comparable: 93.3% vs. 95.7% (P = 0.68) and 97.6% vs. 93.2% (P = 0.62), respectively. Two major complications (one per group) occurred (p = 0.99). ROSE- patients more often reported self-limiting post-procedural pain (p < 0.001). Median procedure time for ROSE+ (20 min) and ROSE- (23 min) was comparable (P = 0.06). Median time to review slides in the ROSE- group (12:47 min) was longer than with ROSE+ (7:52 min) (P < 0.001). Mean costs of ROSE- and ROSE+ were comparable: €938.29 (±172.70) vs. €945.98 (±223.38) (P = 0.91), respectively. CONCLUSIONS: Diagnostic yield and accuracy of EUS-FNA of mediastinal and abdominal lymph nodes with and without ROSE are comparable. Time needed to review slides was shorter and post-procedural pain was less often reported in the ROSE+ group. Based on the primary outcome, the implementation of ROSE during EUS-FNA of mediastinal and abdominal lymph nodes cannot be advised. (Dutch Trial Register: NTR4876).

Is ultrasound-guided fine-needle aspiration cytology of adequate value in detecting breast cancer patients with three or more positive axillary lymph nodes?

This study evaluated the accuracy of ultrasound-guided fine-needle aspiration cytology of the sonographically most suspicious axillary lymph node (US/FNAC) to select early breast cancer patients with three or more tumour-positive axillary lymph nodes. Between 2004 and 2014, a total of 2130 patients with histologically proven early breast cancer were evaluated and treated in the Noordwest Clinics Alkmaar. US/FNAC was performed preoperatively in all these patients. We analysed the results of US/FNAC retrospectively. Pathological axillary node status (sentinel node biopsy and/or axillary lymph node dissection) was used as reference standard. A total of 634 (29.8 %) of 2130 patients had axillary lymph node metastases on final histology. 248 node positive patients (11.6 %) had three or more positive lymph nodes. The accuracy of US/FNAC to detect three or more positive lymph nodes was 89.8 %, sensitivity was 44.8 %, specificity was 95.7 %, PPV was 58.1 %, and NPV was 92.9 %. This study shows a more than adequate accuracy of preoperative US/FNAC to detect three or more positive lymph nodes (89.8 %). However, when US/FNAC was chosen as the only axillary staging method, 6.4 % of all patients (false negative group) would have been undertreated and 3.8 % of all patients (false positive group) would have been overtreated according to the ACOSOG Z0011 criteria.

Smoking is Associated With Extra-intestinal Manifestations in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Smoking affects the course of disease in patients with ulcerative colitis (UC) and Crohn's disease (CD). We aimed to study the association between smoking and extra-intestinal manifestations (EIMs) in inflammatory bowel disease (IBD). METHODS: We cross-sectionally explored the association between smoking and EIMs in IBD in three cohort studies: (1) the COIN study, designed to estimate healthcare expenditures in IBD; (2) the Groningen study, focused on cigarette smoke exposure and disease behaviour in IBD; and (3) the JOINT study, evaluating joint and back manifestations in IBD. RESULTS: In the COIN, Groningen and JOINT cohorts, 3030, 797 and 225 patients were enrolled, of whom 16, 24 and 23.5% were current smokers, respectively. Chronic skin disorders and joint manifestations were more prevalent in smoking IBD patients than in non-smokers (COIN, 39.1 vs 29.8%, p <0.01; Groningen, 41.7 vs 30.0%, p <0.01) in both CD and UC. In the JOINT cohort, smoking was more prevalent in IBD patients with joint manifestations than in those without (30.3 vs 13.0%, p <0.01). EIMs appeared to be more prevalent in high- than in low-exposure smokers (56.0 vs 37.1%, p = 0.10). After smoking cessation, the prevalence of EIMs in IBD patients rapidly decreased towards levels found in never smokers (lag time: COIN cohort, 1-2 years; Groningen cohort, within 1 year). CONCLUSIONS: There is a robust dose-dependent association between active smoking and EIMs in both CD and UC patients. Smoking cessation was found to result in a rapid reduction of EIM prevalence to levels encountered in never smokers.

Defining consensus leukemia-associated immunophenotypes for detection of minimal residual disease in acute myeloid leukemia in a multicenter setting.

Flow-cytometric detection of minimal residual disease (MRD) has proven in several single-institute studies to have an independent prognostic impact. We studied whether this relatively complex approach could be performed in a multicenter clinical setting. Five centers developed common protocols to accurately define leukemia-associated (immuno)phenotypes (LAPs) at diagnosis required to establish MRD during/after treatment. List mode data files were exchanged, and LAPs were designed by each center. One center, with extensive MRD experience, served as the reference center and coordinator. In quarterly meetings, consensus LAPs were defined, with the performance of centers compared with these. In a learning (29 patients) and a test phase (35 patients), a mean of 2.2 aberrancies/patient was detected, and only 1/63 patients (1.6%) had no consensus LAP(s). For the four centers without (extensive) MRD experience, clear improvement could be shown: in the learning phase, 39-63% of all consensus LAPs were missed, resulting in a median 30% of patients (range 21-33%) for whom no consensus LAP was reported; in the test phase, 27-40% missed consensus LAPs, resulting in a median 16% (range 7-18%) of 'missed' patients. The quality of LAPs was extensively described. Immunophenotypic MRD assessment in its current setting needs extensive experience and should be limited to experienced centers.

Contralateral axillary lymph node metastases at the time of primary breast cancer diagnosis: curative or palliative intent?

Contralateral axillary lymph node metastases (CAMs) in breast cancer patients are uncommon. CAM can be found at the time of primary breast cancer diagnosis or following prior treatment of breast cancer as a recurrence. This distinction may have important implications for disease staging and treatment selection. We report the case of a premenopausal woman with synchronous CAM. Despite extensive multimodality treatment, a recurrence was found 27 months after primary surgery. We reviewed the literature on histopathological tumor characteristics associated with CAM, lymphatic drainage of the breast to other sites than the ipsilateral axilla, and outcome of cases with CAM. This case contradicts current conceptions that CAM only develops from tumors with poor histopathological features. Emerging evidence shows that altered lymphatics play a central role in development of synchronous CAM. It is precisely this etiology that supports the concept that synchronous CAM occurs by lymphatic spread and not by hematogenous spread. Although controversial, treatment of synchronous CAM (without evidence of distant metastases) should therefore be of curative intent.

[Practical guidelines for the treatment of cases of adder envenomation in dogs]. / Praktische richtlijnen voor de behandeling van adderbeten bij de hond.

Every year, dogs are presented to veterinary clinics in the Netherlands after having been bitten by a viper. The viper is the only venomous snake native to the Netherlands. Clinical signs after an acquired viper bite can range from none (after a 'dry' bite) to very mild up to life threatening following a 'wet' bite. To prevent mortality it is important to monitor the animals for a period of time and provide adequate treatment. Clotting disorders and multiple organ failure can occur several days to a week after the viper bite, appropriate follow up is therefore important. In the Netherlands, a specific antiserum is available for veterinarians. The use of this antiserum is strongly recommended in severe cases of viper envenomation.

Ultrasound and fine needle aspiration cytology of axillary lymph nodes in breast cancer. To do or not to do?

AIM: The purpose of our study was to evaluate the accuracy of axillary ultrasound and ultrasound-guided fine needle aspiration cytology (FNAC) in the preoperative diagnosis of axillary metastases. METHODS: Between 2004 and 2009, 1132 female patients were evaluated and treated in our clinic for histologically proven breast carcinoma. Preoperative axillary ultrasound with subsequent FNAC in case of suspicious lymph nodes was performed in 1150 axillae (18 bilateral breast carcinomas). We analyzed the results of axillary ultrasound and FNAC retrospectively. Pathological node status was used as the reference standard (based on axillary dissection or sentinel node biopsy). RESULTS: Axillary ultrasound showed suspicious lymph nodes in 327 axillae (28.4%). FNAC showed axillary metastases in 107 of these 327 axillae. Final histological analysis confirmed 106 metastases (one false positive). Histological analysis showed metastatic disease in 429 of 1150 axillae (37.3%). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of axillary ultrasound alone were 43.8% (188/429), 80.7% (582/721), 57.5% (188/327) and 70.7% (582/823), respectively. When combining axillary ultrasound with FNAC of suspicious lymph nodes, sensitivity was 24.7% (106/429), specificity was 99.9% (720/721), PPV was 99.1% (106/107) and NPV was 69.0% (720/1043). CONCLUSIONS: 106/429 (24.7%) Node-positive axillae were identified by ultrasound-guided FNAC and spared unnecessary sentinel node biopsy. Unfortunately, the percentage of false negative results of ultrasound-guided FNAC (28.1%, 323/1150) was very high.

Oculomotor behavior of hemianopic chronic stroke patients in a driving simulator is modulated by vision training.

BACKGROUND: Visual Restorative function training aims to decrease visual field defect size after acquired brain damage. Some chronic stroke patients regain permission to drive a car after training. This points to a concomitant change in oculomotor behavior, because visual field enlargement is hardly ever large enough for legal driving. This study investigated vRFT-induced changes in oculomotor behavior, using a driving simulator. METHODS: Driving performance and oculomotor behavior were measured before and after training in 6 hemianopia patients who had trained 65 hours with vRFT on a PC at home. RESULTS: Two patients showed negligible visual field enlargement (VFE) and four showed moderate to substantial VFE. Because less visual cortex is devoted to the processing of peripheral than central visual field the same VFE corresponds to less functional restoration of cortex when the defect is at high eccentricity. When this is taken into account, then precisely the two patients that showed the largest cortical gains made significantly more eye movements in the direction of their visual field defect after training. CONCLUSIONS: vRFT with mandatory eye fixation can result in increased eye movement behavior towards the defect. Our study suggests that a threshold amount of cortical functional restoration is required for this effect.

[Burnout, work characteristics and retirement intentions]. / Burnout en pensioenplannen bij oudere werknemers.

We investigated whether there is a relationship between burnout and work characteristics and retirement intentions from older workers. Data were taken from a survey held among Dutch older workers (50+) and their spouses (N=2,892). The results show that high workload, heavy physical work, and lack of challenge are related to burnout. No effect, however, was found for competence. Besides the effect of burnout, retirement intentions are related to the level of marital quality. Older workers who report a higher level of marital quality report a stronger intention to retire. Burnout and retirement intentions are related, but appear to be two different processes. While burnout can generally be explained by the work environment, nonwork related factors enhance our understanding of retirement intentions. This study shows that actual retirement is often preceded by feelings of burnout, in particular a mental detachment from work and feelings of exhaustion.

Three-color flowcytometric analysis of mature and immature hematological malignancies. A guideline of the Dutch Foundation for Immunophenotyping of Hematological Malignancies (SIHON).

Multiparameter flowcytometry offers an insight into differentiation pathways, maturation stages and abnormal features of cell (sub)populations thus helping to establish and classify hematological malignancies. The Dutch Foundation for Immunophenotyping of Hematological Malignancies (SIHON) has formulated a guideline for a rapid screening followed by confirmation and classification in a standardized way. For this aim seven carefully composed monoclonal antibody combinations are elucidated for screening the test sample in a first phase. In this phase a relative frequency distribution of the cells will be established and a decision will be made about abnormal cells present, as well as their mature or immature state and the cell lineage they belong to. In a second phase, panels with cell lineage dependent monoclonal antibody combinations may be used to confirm and classify the abnormal cell population indicated in phase 1, as well as to establish the presence or absence of an abberant immunophenotype.

Increased production of interleukin 4 by CD4+ and CD8+ T cells from patients with tuberculosis is related to the presence of pulmonary cavities.

In tuberculosis, cellular immunity is considered to be responsible for the eradication of infection but also for damage of host tissues. In animal models, the balance between Th1-type cytokines, especially interferon (IFN)-gamma, and Th2-type cytokines, primarily interleukin (IL)-4, seems crucial for these effects. Reports on Th1-type and Th2-type cytokines in human tuberculosis are conflicting, and little is known about their role in tissue damage. Flow-cytometric assessment of cytokine responses was performed in human immunodeficiency virus (HIV)-seronegative patients with active tuberculosis and in healthy controls. Patients and controls showed no significant difference in expression of IFN-gamma. However, patients showed a striking increase in production of IL-4 in CD4+ as well as CD8+ T cells. Most remarkably, the expression of IL-4 was especially elevated in patients with cavitary tuberculosis. The Th2-type response with increased production of IL-4 in patients with tuberculosis may antagonize host defense and lead to tissue necrosis.

Bacterial filters in anesthesia: results of 9 years of surveillance.

In 9 years of surveillance of postoperative lower respiratory infections, the infection rate in patients following regional anesthesia was 0.2% and 0.1% in patients following general anesthesia. No bacterial filters in the breathing circuit were used. Infected patients had risk factors such as type of surgery, American Society of Anesthesiologists class > or =2, old age, chronic obstructive pulmonary disease, or smoking habits. Infections were not clustered. This suggests that, in our setting, patient factors are most important in the development of postoperative lower respiratory infections and that the role of bacterial filters as a preventive measure is negligible.