Insights into the concept of vitality: associations with participation and societal costs.

BACKGROUND: In healthcare, the focus is currently shifting from someone's disabilities to someone's abilities, which is also evident from the increasing focus on vitality. Vitality (here defined as energy, motivation and resilience) is an often used concept, which also aims at someone's capabilities. However, little is known about vitality yet; in particular about its association with participation and societal costs. METHODS: Within a cross-sectional design, information regarding vitality, participation and societal costs was collected among 8015 Dutch adults aged 20 years and over. Vitality was measured using the validated Dutch Vitality Questionnaire (Vita-16). Information on economic (i.e. want/able to work, work absenteeism, work performance), societal (i.e. voluntary work, informal care giving) and social participation (i.e. quantity and quality of social contacts) and societal costs (i.e. healthcare and work-related costs) was collected using an internet survey. RESULTS: Significant associations were found between vitality and various economic (i.e.sustainable employability:want to work: ß = 1.21, 95% CI: 0.99-1.43,able to work:ß = 2.09, 95% CI: 1.79-2.38;work absenteeism: OR = 0.75, 95% CI: 0.71-0.79;work performance:ß = 0.49, 95% CI: 0.46-0.52), societal (i.e.voluntary work, informal care) and social (i.e.quantity and quality of social contacts) participation measures, as well as between vitality and societal costs (i.e.healthcare costs:ß = -213.73, 95% CI: €-311.13 to €-107.08),absenteeism costs: ß = -338.57, 95% CI: €-465.36 to €-214.14 and presenteeism costs:ß = -1293.31, 95% CI: €-1492.69 to €-1088.95). CONCLUSION: This study showed significant positive associations between vitality and economic, societal and social participation and negative associations between vitality and societal costs. This may stimulate research on interventions enhancing and maintaining vitality and thereby contributing to improved participation and reduced costs.

Rituximab as induction therapy after renal transplantation: a randomized, double-blind, placebo-controlled study of efficacy and safety.

We evaluated the efficacy and safety of rituximab as induction therapy in renal transplant patients. In a double-blind, placebo-controlled study, 280 adult renal transplant patients were randomized between a single dose of rituximab (375 mg/m(2)) or placebo during transplant surgery. Patients were stratified according to panel-reactive antibody (PRA) value and rank number of transplantation. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil and steroids. The primary endpoint was the incidence of biopsy proven acute rejection (BPAR) within 6 months after transplantation. The incidence of BPAR was comparable between rituximab-treated (23/138, 16.7%) and placebo-treated patients (30/142, 21.2%, p = 0.25). Immunologically high-risk patients (PRA >6% or re-transplant) not receiving rituximab had a significantly higher incidence of rejection (13/34, 38.2%) compared to other treatment groups (rituximab-treated immunologically high-risk patients, and rituximab- or placebo-treated immunologically low-risk (PRA ≤ 6% or first transplant) patients (17.9%, 16.4% and 15.7%, p = 0.004). Neutropenia (<1.5 × 10(9) /L) occurred more frequently in rituximab-treated patients (24.3% vs. 2.2%, p < 0.001). After 24 months, the cumulative incidence of infections and malignancies was comparable. A single dose of rituximab as induction therapy did not reduce the overall incidence of BPAR, but might be beneficial in immunologically high-risk patients. Treatment with rituximab was safe.

Membranous nephropathy with predominance of C1q: another variant of C1q nephropathy?

Originally described as a proliferative glomerulonephritis, C1q nephropathy is nowadays mostly recognized as a variant of focal segmental glomerulosclerosis or minimal change disease. We describe a 30-year-old male patient with nephrotic range proteinuria. Kidney biopsy demonstrated a membranous nephropathy with predominant staining for C1q. Under conservative therapy the outcome was favorable. We suggest that this case represents another variant of C1q nephropathy, thus broadening the spectrum of the disease.

Progressive renal disease despite immunosuppressive therapy in a patient with Wegener s granulomatosis.

We present a patient with Morbus Wegener and crescentic glomerulonephritis. Treatment with cyclophosphamide and prednisolone resulted in the disappearance of signs and symptoms of systemic inflammation. However, renal function deteriorated. Renal biopsy showed evidence of continuing capillary necrosis. Renal function improved with added plasmapheresis treatment. This case report illustrates that in patients with vasculitis necrotizing glomerulonephritis may remain active despite immunosuppressive therapy, even in the absence of extrarenal disease activity.

Review on diagnosis and treatment of focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is one the most important causes of the nephrotic syndrome in adult patients. FSGS is not a disease entity. The identification of underlying causes of FSGS (secondary FSGS) has increased our insight into the pathogenesis of FSGS. Moreover, differentiating between primary (idiopathic) and secondary forms of FSGS is important to allow appropriate treatment. Recently a new pathological classification of FSGS was proposed, expanding FSGS to include nonsclerotic lesions. In this review we discuss the current diagnostic and therapeutic options in patients with FSGS.

Progressive kidney failure in chronic myelomonocytic leukaemia: don't forget lysozyme damage.

Kidney failure is common in haematologic malignancies. However, the nephrotoxic effect of lysozyme is seldom recognized. We present a 78-year-old male with chronic myelomonocytic leukaemia who developed progressive kidney failure due to increased production of lysozyme.

Fibrillary glomerulonephritis in a patient with type 2 diabetes mellitus.

We report a 62-year-old man with documented type 2 diabetes mellitus and hypertension, who presented with a rapid deterioration in renal function. The sudden decrease in renal function in this well-controlled diabetic patient prompted us to consider a nondiabetic and nonhypertensive cause. The urinary sediment showed a glomerular haematuria suggestive of glomerulonephritis. A diagnosis of fibrillary glomerulonephritis was made on renal biopsy. Fibrillary glomerulonephritis is a rarely diagnosed disease with clinical manifestations such as proteinuria, microscopic haematuria, nephrotic syndrome and impairment of renal function. A diagnosis of fibrillary glomerulonephritis can only be made by electronmicroscopy of the renal tissue. In this case report the spectrum of this disease is reviewed.

Familial focal segmental glomerulosclerosis: mutation in inverted formin 2 mimicking Alport syndrome.

Focal segmental glomerulosclerosis (FSGS) is one of the most common patterns of glomerular injury. FSGS can be caused by mutations in genes encoding proteins that play key roles in the function of the podocyte and glomerular basement membrane. In this case report we present a family with FSGS initially suspected to be Alport syndrome. Genetic analysis according to the Dutch guidelines of FSGS revealed a mutation in INF2.

IgH/TCR delta PCR oligonucleotide liquid hybridization, a fast and sensitive assay for monitoring minimal residual disease in childhood B-precursor ALL.

The detection of minimal residual disease (MRD) in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR) may turn out to be a powerful tool in the evaluation and guidance of therapy. Most previously described techniques are highly sensitive but also too laborious for application in a routine setting. Here we describe a technique based on the determination of IgH VHDJH and TCR V delta 2D delta 3 junctional regions by PCR/cycle sequencing analysis and hybridization of junctional region oligonucleotide probes in a standard liquid hybridization (LH) assay. We systematically analyzed the applicability of this simplified approach for the monitoring of MRD in a large patient group. IgH VHDJH and TCR V delta 2D delta 3 junctional regions were amplified from presentation bone marrow samples obtained from 53 childhood B-precursor ALL patients. The combined approach allowed the identification of at least one tumor marker for 49/53 (92.5%) of patients. A total of 75 oligonucleotide probes (54 DJH, 21 V delta 2D delta 3) was tested in the LH assay. Sensitivity range was 10(-2)-10(-5) and 10(-4)-10(-5) for DJH and V delta 2D delta 3 junctional region probes, respectively. A sensitivity of at least one malignant cell in 10(4) normal cells was obtained for 84.8% of evaluable patients, applying on average 1.1 IgH and 0.47 TCR delta probes per patient. Comparison to a method based on the use of initial PCR product as clone-specific probe showed that oligonucleotide LH was one log more sensitive in six of nine patients tested. The presented technique allows the monitoring of MRD with acceptable sensitivities in over 90% of childhood B-precursor ALL patients. Moreover, the technique is suitable for prospective patient studies in a routine setting as it is fast, reproducible and makes use of a standard hybridization protocol for different oligonucleotide probes.

Prolonged persistence of PCR-detectable minimal residual disease after diagnosis or first relapse predicts poor outcome in childhood B-precursor acute lymphoblastic leukemia.

The follow up of minimal residual disease (MRD) in childhood B-precursor ALL by polymerase chain reaction (PCR) may be of help for further stratification of treatment protocols, to improve outcome. However, the clinical relevance of this approach has yet to be defined. We report the retrospective follow-up of MRD in bone marrow (BM) samples from 50 childhood B-precursor ALL patients by IgH/TCR delta PCR. Twenty-two patients remained in continuous complete remission (median follow-up 61 months), and 28 experienced relapse (median follow-up 75 months). Initial regression of MRD on therapy correlated with outcome. At the end of induction therapy 2/18 (11.1%) patients from the CCR group were PCR positive vs 10/16 (62.5%) from the 'relapse' group (P = 0.005). The presence of PCR detectable MRD predicted event-free survival independent of standard clinical and cytogenetical parameters. Also subsequent to first BM relapse, a correlation between MRD regression and outcome was observed. Six of eight patients who became PCR negative in the time period between relapse and bone marrow transplantation are in CCR, whereas 7/7 patients who remained PCR positive in this time period died (P = 0.006). In approximately 70% of evaluable patients, clinical relapse was preceded by recurrence of detectable MRD at time intervals of 3-18 months earlier and the recurrence of PCR positivity after a period of negativity was always followed by overt relapse. At relapse, the combined use of IgH and TCR delta probes reduced false negativity caused by clonal evolution to approximately 10%. This study shows that the evolution of PCR detectable MRD is an independent predictor of outcome.

Rearrangement status of the malignant cell determines type of secondary IgH rearrangement (V-replacement or V to DJ joining) in childhood B precursor acute lymphoblastic leukemia.

Immunoglobulin heavy chain (IgH) oligoclonality in childhood B precursor acute lymphoblastic leukemia (ALL) as determined by Southern analysis is found in 30-50% of patients and has been shown to be the result of ongoing IgH rearrangement (mostly V(H)-replacement and V(H) to D-J(H) joining) after malignant transformation. It is unknown however, what determines the type of secondary rearrangement. Also the biological basis of the variable degree of oligoclonality observed in childhood ALL is poorly understood. We analyzed in detail the IgH rearrangement status of the leukemic cells for a random panel of 18 childhood B precursor ALL patients by polymerase chain reaction (PCR)/sequencing analysis and by Southern analysis. By Southern analysis 10/18 (55.6%) patients were considered oligoclonal and 8/18 (44.4%) monoclonal. In contrast, by PCR minor clonal rearrangements were detected in 14/18 (77.8%) patients. V(H)-replacement was found in 7/14 patients, V(H) to D-J(H) joining in 6/14 patients and an unusual type of secondary rearrangement, V(H)-D to J(H) joining, in one patient. Only a single type of secondary rearrangement was detected in each patient. The type of secondary rearrangement (V(H)-replacement or V(H) to D-J(H) joining) depended on the rearrangement status (VDJ/VDJ or VDJ/DJ, respectively) of the dominant leukemic clone as determined by Southern analysis. We found that in addition to a more 'advanced' IgH rearrangement status patients with V(H)-replacements also have a more 'advanced' TCRdelta rearrangement status, which possibly reflects exposure of both the IgH locus and the TCRdelta locus to recombinase activity in a preleukemic clone. Finally, we investigated a putative relationship between oligoclonality by Southern analysis and S-phase fraction of the leukemic cell population. We found a significantly lower percentage cells in S-phase for oligoclonal patients as compared to monoclonal patients. Our data add to the understanding of ongoing rearrangement of antigen receptor loci in childhood ALL and have implications for the monitoring of minimal residual disease by PCR.

Clonal evolution of immunoglobulin heavy chain rearrangements in childhood B-precursor acute lymphoblastic leukemia after engraftment in SCID mice.

We grafted childhood B-precursor acute lymphoblastic leukemia (ALL) bone marrow (BM) cells into mice with severe combined immunodeficiency (SCID), in order to study the clonal evolution of immunoglobulin heavy chain (IgH) rearrangements in the absence of selective pressure by chemotherapy. BM cells from nine patients (six diagnosis samples and three relapse samples) were intravenously injected into SCID mice (three mice for each patient). All mice injected with cells from four patients developed a leukemia-like illness 12-40 weeks after injection. By PCR, new subclones that were the result of ongoing IgH rearrangement according to the mechanism operative in the injected cell populations (VH-replacement or VH to D-JH joining) were detected in the engrafted cell populations for all four patients. Subclones were mouse-specific, suggesting that subclone formation is a continuous process. Southern analysis after engraftment was unaltered as compared to the injected cells for one patient and revealed changes indicative of altered clonal composition for three patients. For two patients the observed changes possibly reflect the initial engraftment of a limited number of cells and occurred without changes in other parameters of the engrafted cell population, such as time needed for the development of leukemia, macroscopic organ involvement, immunophenotype and S-phase fraction. In one patient, we demonstrated the selective outgrowth of only a single cell type present at diagnosis, as characterized by IgH rearrangements. Our data show that evolution of clonal IgH rearrangements in B-precursor ALL may occur without the selective pressure of chemotherapy. Additionally, in some patients subclones present at diagnosis, as defined by IgH rearrangements, also possess different biological properties.

Idiopathic focal segmental glomerulosclerosis: a favourable prognosis in untreated patients?

BACKGROUND: Patients with focal segmental glomerulosclerosis (FSGS) are considered to have a poor prognosis and spontaneous remissions are seldom reported. However, FSGS is not a single disease entity. Our aim was to describe the clinical course in initially untreated patients with recently diagnosed idiopathic FSGS. METHODS: This was a retrospective study of patients with a diagnosis of FSGS by histology, who fulfilled the following criteria: proteinuria >3.5 g/day, normal renal function, duration of proteinuria or hypertension of less than one year, normal-sized kidneys, no underlying renal disease, and a negative family history. Renal biopsies were reviewed without knowledge of the clinical course. RESULTS: Twenty patients (13 male, 7 female) fulfilled the study criteria. Median age was 49.3 (range 21.8 to 73.0) years, serum creatinine 90 +/- 20 micromol/l, proteinuria 10.0 +/- 5.5 g/day and serum albumin 24 +/- 6 g/l. After a median follow-up of 9.4 (2.1-18.6) years, 13 patients (65%) were in remission of proteinuria. Renal function deterioration occurred in seven patients, and prompted treatment in four of them. The ten-year death-censored renal survival was 89%. Renal function deterioration and remission rate could be predicted by selectivity index, serum albumin at three months after renal biopsy and the percentage of glomeruli with segmental sclerosis. CONCLUSION: Focal glomerulosclerosis is not a single disease. Case definition using strict clinical criteria identifies a subgroup of patients with idiopathic FSGS who have a good prognosis. In the majority of these patients immunosuppressive therapy is not warranted.

The influence of force magnitude on intrusion of the maxillary segment.

The purpose of this study was to determine whether the magnitude of intrusive force to the maxillary incisors influences the rate of incisor intrusion or the axial inclination, extrusion, and narrowing of the buccal segments. Twenty patients between the ages of nine and 14 years who needed at least two mm of maxillary incisor intrusion were assigned to one of two equal groups. In group 1 patients, the teeth in the maxillary anterior segment were intruded using 40 g, whereas in group 2 patients, 80 g was used. Records were taken from each patient at the beginning and end of intrusion. There was no statistically significant difference between the 40- and 80-g groups in the rate of incisor intrusion, or the amount of axial inclination change, extrusion, and narrowing of the buccal segments.

The relation between the point of force application and flaring of the anterior segment.

The purpose of this study was to determine whether application of an intrusive force by an intrusion arch at the distal wings of the lateral incisor brackets causes a change in the axial inclination of the anterior segment. Maxillary incisor intrusion was performed, and records were taken from 40 adolescent patients at the beginning and end of intrusion. Intrusion of the maxillary anterior segment caused a statistically significant mean increase in axial inclination of the central incisor of 8.74 degrees. The following correlations were investigated and found not statistically significant. The correlation between the (1) distance from the point of force application to the center of resistance at the start of intrusion and the change in axial inclination of the incisor, (2) distance from the point of force application to the center of resistance at the start of intrusion and the change in distance from the incisal edge to the distal side of the first molar, (3) distance from the point of intrusive force application to the center of resistance at the start of intrusion and at the end of intrusion, (4) distance from the point of intrusive force application to the center of resistance at the start of intrusion and the change in this distance between start and end of intrusion, and (5) amount of intrusion and the change in axial inclination.

The role of a high pull headgear in counteracting side effects from intrusion of the maxillary anterior segment.

Intrusion of incisors is often the preferred treatment of a deep overbite. This study focuses on deep overbite correction by intrusion of maxillary incisors. The purpose of this study is to determine whether high-pull headgear wear can prevent steepening of the buccal segment, extrusion of the buccal segment, maintain arch width, and increase the rate of incisor intrusion. The number of patients needed for this study was calculated to be 20. Patients were between nine and 14 years of age and assigned to one of two groups. In each group, intrusion of maxillary incisors was performed. Patients in one group wore a high-pull headgear at night, and patients in the other group did not. For each patient, a lateral head film, impressions with a wax bite in centric occlusion, and intraoral photographs were taken at the beginning and end of intrusion. This study demonstrated that high-pull headgear had no effect on steepening and extrusion of the buccal segments or on the rate of intrusion but did have an effect on narrowing of the buccal segments. By performing intrusion as described in this study, no statistically significant side effects were observed in the buccal segments, whereas a statistically significant amount of incisor intrusion of 2.24 mm in the no-headgear group and 2.37 mm in the headgear group was observed.

[Children with acute lymphoblastic leukemia: prognostic significance of polymerase-chain-reaction analysis of minimal residual disease]. / Kinderen met acute lymfoblastenleukemie: de prognostische betekenis van analyse door middel van de polymerase-kettingreactie van minimale residuale ziekte.

OBJECTIVE: Determination of the usefulness of polymerase chain reaction (PCR) for the detection of minimal residual disease (MRD) in bone marrow in children suffering from progenitor-B cell acute lymphoblastic leukaemia during and after treatment. DESIGN: Descriptive. SETTING: Emma's Children's Hospital, Academic Medical Centre, University of Amsterdam and Central Laboratory of the Dutch Red Cross, Amsterdam. METHOD: Of 50 children suffering from progenitor-B cell ALL, stored bone marrow samples and bone marrow slides were investigated: 328 bone marrow samples were analysed by PCR for IgH/TCR delta; 34 patients were analysed at the end of induction therapy. Follow-up period was 20 to 133 months. RESULTS: Twenty-two patients stayed in continuous complete remission (CCR), 28 patients experienced a recurrence (REC). Reduction of tumour mass was higher in the CCR group. At the end of induction therapy 2/18 CCR patients and 10/16 REC patients were PCR positive (p = 0.005). PCR positivity was not related with known prognostic factors. After recurrence 6/8 patients, who became PCR negative, stayed in remission. All patients who stayed positive after treatment for their recurrence died from leukaemia (p = 0.006). All children who were only temporary PCR negative suffered a recurrence. CONCLUSION: Analysis of MRD by means of PCR on bone marrow samples during and after treatment for progenitor-B cell ALL is of prognostic importance.

Kidney injury during VEGF inhibitor therapy.

Antiangiogenic therapy targeting vascular endothelial growth factor (VEGF) or its receptor (VEGFR) has proven its effect in the treatment of several types of cancer, including renal cell carcinoma (RCC). However, treatment can be accompanied by notable adverse effects. Mild proteinuria and hypertension are often seen, but sometimes nephrotic range proteinuria and÷or renal insufficiency develop. In recent years insight into the toxic effects of anti-VEGF therapy in the kidney has increased. A few biopsies have been done and thrombotic microangiopathy is reported in the majority of cases. However, other patterns of kidney injury have been described as illustrated by the case of a 62-year-old patient who presented two years after initiation of the VEGFR inhibitor cediranib with a nephrotic syndrome and acute renal failure. Kidney biopsy disclosed focal segmental glomerulosclerosis (FS GS) and interstitial nephritis. Partial remission was achieved after stopping the cediranib and a short course of prednisone. We review the different forms of kidney injury that could be caused by anti-VEGF therapy.