Histopathology of leukaemic non-Hodgkin's lymphoma in bone marrow

Staging biopsies of the bone marrow in lymphoma patients are among the most important indications and therefore of substantial practical importance. Occasionally it is the only organ infiltrated, and therefore a bone marrow biopsy is the prime diagnostic choice in cases of leukemic lymphomas. A synoptical diagnostic approach relying on immunophenotypic as well as on molecular biological criteria aside from histomorphology (cytomorphology), is of utmost importance for the subtyping of malignant lymphomas. This too can be done reliably on bone marrow biopsies, as comparative studies have yielded a concordance rate of more than 90% with lymphoma typing on corresponding lymph nodes. Cytology and the pattern of infiltrates, (i.e. diffuse, interstitial, nodular peritrabecular and intrasinusoidal), in combination with immunological phenotyping are the mainstays for subtyping, giving clear-cut decisions in most cases of small B-cell lymphoma, mantle zone as well as marginal cell and follicular lymphomas and hairy cell leukemia. Among the blastic variants the most important are the lymphoblastic lymphomas of either B- or T-cell type which have to be discerned from AML and the so-called blastoid mantle cell lymphomas. T-cell lymphomas are rare compared to B-cell lymphomas. Among the rarely seen T-cell neoplasias the lymphoma of large granular lymphocytes is the dominating lymphoma, which in most cases can only be diagnosed reliably by molecular biological means, followed by T-CLL, Sezary's syndrome and hepatosplenic chi delta lymphoma.     

Effect of depressive symptoms on survival after heart transplantation

OBJECTIVE: This study explored the value of preoperative self-reported assessment for depression and anxiety in patients who had undergone heart transplantation (HTx). The initial sample was divided into subgroups of patients with ischemic (ICMP) and dilated cardiomyopathy (DCMP). Patient depression and anxiety scores were measured in both subgroups and their impact on pre- and postoperative mortality investigated. METHOD: An initial sample of 152 patients with either ICMP (N = 57) or DCMP (N = 95) and end-stage heart disease awaiting heart transplantation were assessed in a multidimensional longitudinal study, including psychological and somatic variables. One hundred and three patients received a HTx and were followed up for a mean of 4.4 years. Proportional hazard models were computed to test for the influence of psychosocial and somatic factors on outcome. RESULTS: Preoperative depression and state anxiety scores were significantly higher in the ICMP group. In addition to donor and recipient age, ICMP patients in the preoperative high depression group also showed a significantly higher mortality after HTx. This result remained significant even after controlling for sociodemographic and somatic variables. CONCLUSIONS: Patient self-reported depression, but not anxiety, can contribute to the identification of subgroups of patients with an unfavorable outcome after HTx. It therefore may be helpful to screen for depression, particularly in patients with an ischemic cause of their end-stage heart disease. Specific intervention programs should be further developed and evaluated.     

Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals,improved with anti-human herpes virus treatment

Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immunodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lymphocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diagnosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings'' health.     

Self-assembled composite matrix in a hierarchical 3-D scaffold for bone tissue engineering

It is of high clinical relevance in bone tissue engineering that scaffolds promote a high seeding efficiency of cells capable of osteogenic differentiation, such as human bone marrow-derived mesenchymal stem cells (hMSCs). We evaluated the effects of a novel polycaprolactone (PCL) scaffold on hMSC seeding efficiency, proliferation, distribution and differentiation. Porous PCL meshes prepared by fused deposition modeling (FDM) were embedded in matrix of hyaluronic acid, methylated collagen and terpolymer via polyelectrolyte complex coacervation. Scaffolds were cultured statically and dynamically in osteogenic stimulation medium for up to 28 days. Compared to naked PCL scaffolds, embedded scaffolds provided a higher cell seeding efficiency (t-test, P<0.05), a more homogeneous cell distribution and more osteogenically differentiated cells, verified by a more pronounced gene expression of the bone markers alkaline phosphatase, osteocalcin, bone sialoprotein I and bone sialoprotein II. Dynamic culture resulted in higher amounts of DNA (day 14 and day 21) and calcium (day 21 and day 28), compared to static culture. Dynamic culture and the embedding synergistically enhanced the calcium deposition of hMSC on day 21 and day 28. This in vitro study provides evidence that hybrid scaffolds made from natural and synthetic polymers improve cellular seeding efficiency, proliferation, distribution and osteogenic differentiation.     

Analyses of muscle spindles in the soleus of six inbred mouse strains

Adult muscle size and fibre‐type composition are heritable traits that vary substantially between individuals. We used inbred mouse strains in which soleus muscle mass varied by an order of magnitude to explore whether properties of muscle spindles can also be influenced by genetic factors. Skip‐serial cross‐sections of soleus muscles dissected from 15 male mice of BEH, BEL, C57BL/6J, DUH, LG/J and SM/J strains were analysed for number of muscle spindles and characteristics of intrafusal and extrafusal fibres following ATPase staining. The BEL and DUH strains determined the range of: soleus mean size, a 10‐fold difference from 2.1 to 22.3 mg, respectively; the mean number of extrafusal fibres, a 2.5‐fold difference from 497 to 1249; and mean fibre‐cross‐sectional area, three‐fold difference, e.g. for type 1 fibres, from 678 to 1948 μm². The range of mean proportion of type 1 fibres was determined by C57BL/6J (31%) and DUH (64%) strains. The mean number of spindles per muscle ranged between nine (LG/J) and 13 (BEL) (strain effect P < 0.02). Genetic correlations between spindle count and muscle weight or properties of extrafusal fibres were weak and not statistically significant. However, there was a strong correlation between the proportion of spindles with more than one bag₂ fibre and the proportion of extrafusal fibres that were of type 1, and strain‐dependent variation in the numbers of such spindles was statistically significant. The numbers of intrafusal fibres per spindle ranged from 2 to 8, with the most common complement of four found in 75.6% of spindles. There were no significant differences between the strains in the mean numbers of intrafusal fibres; however, the variance of the number was significantly less for the C57BL/6J strain than for any of the others. We conclude that abundance of muscle spindles and their intrafusal‐fibre composition are substantially determined by genetic factors, which are different from those affecting muscle size and properties of the extrafusal fibres.     

Effectiveness and handling characteristics of a three-layer polymer dura substitute: a prospective multicenter clinical study

OBJECT: The goal of this study was to assess the effectiveness and handling characteristics of a dura substitute composed of two outer layers of expanded polytetrafluoroethylene (PTFE) and a middle layer consisting of an elastomeric fluoropolymer. METHODS: In a prospective multicenter study, the dura substitute was implanted using a standard technique in 119 patients undergoing cranial or spinal surgery requiring duraplasty. Intraoperative assessments of the dura patch consisted of testing for cerebrospinal fluid (CSF) leakage employing the Valsalva maneuver and a surgeon's standard evaluation of the handling characteristics of the device. Postoperative assessments conducted during a mean follow-up time of 15.7 months (range 0.3-45.6 months) consisted of physical examinations, routine computed tomography (CT) or magnetic resonance (MR) imaging studies, and histological studies of any removed dura patches. The mean age of the 119 patients was 40 years (range < 1-81 years). The dura substitute was implanted cranially in 102 patients and spinally in 17. Intraoperative assessment including the Valsalva maneuver led to application of additional sutures in 17 patients. Handling features were rated very good to excellent. Postoperative clinical evaluation resulted in 79 excellent and 18 good results. Imaging studies (MR imaging studies in 69 patients and CT studies in 34 patients) showed no adhesions in 87 patients and minimal adhesions in seven patients (the dura was not visualized in nine patients). Postoperative complications occurred in 12 patients. There were six cases of CSF leakage, three cases of extradural hematoma, one case of arachnoid fibrosis after decompression of a Chiari malformation Type I, and two cases of infection. Eight (7%) of these complications were potentially related to the dura patch. CONCLUSIONS: In a large, multicenter clinical study of the use of an expanded-PTFE-containing dura substitute, the device was found to be easy to handle and implant. No serious dura patch-related intraoperative adverse events were observed. Postoperatively, there were no major sealing problems or long-term complications. In two cases the patch had to be removed due to fibrosis and infection. The three-layer polymer dura substitute appears to be safe and effective in minimizing CSF leakage and adhesion formation, and its use avoids any risk of prion disease transmission.     

Prevalence of complications in neuromuscular scoliosis surgery: a literature meta-analysis from the past 15 years

Purpose

Our objectives were primarily to review the published literature on complications in neuromuscular scoliosis (NMS) surgery and secondarily, by means of a meta-analysis, to determine the overall pooled rates (PR) of various complications associated with NMS surgery.

Methods

PubMed and Embase databases were searched for studies reporting the outcomes and complications of NMS surgery, published from 1997 to May 2011. We focused on NMS as defined by the Scoliosis Research Society’s classification. We measured the pooled estimate of the overall complication rates (PR) using a random effects meta-analytic model. This model considers both intra- and inter-study variation in calculating PR.

Results

Systematic review and meta-analysis were performed for 68 cohort and case–control studies with a total of 15,218 NMS patients. Pulmonary complications were the most reported (PR = 22.71 %) followed by implant complications (PR = 12.51 %), infections (PR = 10.91 %), neurological complications (PR = 3.01 %) and pseudoarthrosis (PR = 1.88 %). Revision, removal and extension of implant had highest PR (7.87 %) followed by malplacement of the pedicle screws (4.81 %). Rates of individual studies have moderate to high variability. The studies were heterogeneous in methodology and outcome types, which are plausible explanations for the variability; sensitivity analysis with respect to age at surgery, sample size, publication year and diagnosis could also partly explain this variability. In regard to surgical complications affiliated with various surgical techniques in NMS, the level of evidence of published literature ranges between 2+ to 2−; the subsequent recommendations are level C.

Conclusion

NMS patients have diverse and high complication rates after scoliosis surgery. High PRs of complications warrant more attention from the surgical community. Although the PR of all complications are affected by heterogeneity, they nevertheless provide valuable insights into the impact of methodological settings (sample size), patient characteristics (age at surgery), and continual advances in patient care on complication rates.

Electronic supplementary material

The online version of this article (doi:10.1007/s00586-012-2542-2) contains supplementary material, which is available to authorized users.     

The predictive value of pain drawings in lumbar spinal fusion surgery

Background contextPain drawings have been used extensively in spine surgery. It has been associated with inferior outcome after disc and stenosis surgery. Results regarding the predictive value in fusion surgery have been conflicting.PurposeTo evaluate the predictive value of pain drawings in relation to outcome after lumbar spinal fusion. To investigate if there are differences between spondylolisthesis patients and patients with degenerative disease as well as between patients with or without radicular pain.Study designProspective clinical cohort with a minimum of 1-year follow-up.Patient sampleOne hundred thirty-five patients undergoing lumbar spinal fusion. Fifty-seven men and 78 women, mean age 44 years (range 21–59 years).Outcome measuresDallas Pain Questionnaire (DPQ), Low Back Pain Rating Scale (LBPRS) pain index and patient satisfaction. Minimal clinical important difference was defined for the LBPRS score.MethodsPain drawings were classified, using the visual inspection method, as organic or nonorganic and correlated to outcomes. Multivariate adjustment for several possible confounding variables was done using logistic regression analysis.ResultsThirty-three percent of the drawings were classified as nonorganic. Nonorganic drawings were associated with significantly higher DPQ and LBPRS scores preoperatively and at follow-up. Differences between organic and nonorganic drawings were larger in spondylolisthesis patients than in patients with degenerative disorders. Nonorganic pain drawings were associated with poorer outcome in patients with low back pain and radicular symptoms, however, not in patients without radicular symptoms. A nonorganic pain drawing predicted negative patient satisfaction with odds ratio (OR) 3.01 (95% confidence interval (CI): 1.14–8.55, p=.027) but had no significant predictive value with respect to improvement in the LBPRS pain index OR 1.92 (95% CI: 0.82–4.47, p=.132).ConclusionsA nonorganic pain drawing was a significant risk factor for inferior outcome after spinal fusion surgery. The predictive value did not allow for patient selection.     

Can autologous bone culture predict spinal fusion capacity?

The capacity of the individual patient to initiate osteoblast proliferation as a predictor for successful lumbar spinal fusion has not yet been reported. The objectives of this study were, first, to analyze the relationship between in vitro osteoblast proliferation and clinical bony fusion in the individual patient in order to predict the fusion outcome and, second, to measure the effect of preoperative tobacco smoking on osteoblast proliferation. Sixty-one patients (mean age 46 years) underwent posterolateral lumbar fusion in the period 1994–1995. Thirty-eight patients received CD pedicle screw implants and 23 received posterolateral fusions alone. During surgery, autogenous iliac bone was harvested and 1 g of trabecular bone without blood or bone marrow was then isolated for cell culturing. The cultures were classified as excellent (confluence within 4 weeks), good (confluence between 4 and 6 weeks) and poor (no or poor growth). Spine fusion was evaluated by two independent observers from plain anterior-posterior, lateral, and flexion/extension radiographs taken 1 year postoperatively, and the functional outcome was measured by the Dallas Pain Questionnaire (DPQ). Twenty-three patients had excellent, 19 good, and 19 poor in vitro osteoblast proliferation. Bony fusion was obtained in 77% of patients: 83% in the CD instrumentation group and 70% in the non-instrumentation group (NS). There was no significant correlation between osteoblast proliferation and spinal fusion or functional outcomes when analyzing the CD instrumentation and non-instrumentation groups together or separately. Elderly patients had a significantly poorer osteoblast proliferation than younger patients (P < 0.008). Preoperative tobacco consumption had no discernible effect on osteoblast proliferation, and no correlation between smoking and fusion was found. Further refinement of autologous osteoblast culturing may provide a biological tool for selection of patients who require biological enhancement of their bone fusion capacity. The poorer osteoblast proliferation related to advanced age supports the important negative biological influence of age on bony fusion. However, with more sensitive testing and better discrimination, other results are possible – or can in any event not be excluded. Received: 17 April 1998 Revised: 10 September 1998 Accepted: 12 October 1998