[Treatment recommendations in cardio-oncology: where are we?] / Therapieempfehlungen in der Kardioonkologie ­ wo stehen wir?

This article provides an overview of current prevention and treatment options for typical cardiovascular side effects of oncological therapies as well as cardiovascular complications of malignant disease. Focus is put on the prevention and treatment of heart failure under potentially cardiotoxic cancer therapies. In addition, current options for the treatment of common venous thromboembolism in cancer patients will be discussed.

Factor analysis of the SRS-22 outcome assessment instrument in patients with adult spinal deformity.

PURPOSE: Designed for patients with adolescent idiopathic scoliosis, the SRS-22 is now widely used as an outcome instrument in patients with adult spinal deformity (ASD). No studies have confirmed the four-factor structure (pain, function, self-image, mental health) of the SRS-22 in ASD and under different contexts. Factorial invariance of an instrument over time and in different languages is essential to allow for precise interpretations of treatment success and comparisons across studies. This study sought to evaluate the invariance of the SRS-22 structure across different languages and sub-groups of ASD patients. METHODS: Confirmatory factor analysis was performed on the 20 non-management items of the SRS-22 with data from 245 American English-, 428 Spanish-, 229 Turkish-, 95 French-, and 195 German-speaking patients. Item loading invariance was compared across languages, age groups, etiologies, treatment groups, and assessment times. A separate sample of SRS-22 data from 772 American surgical patients with ASD was used for cross-validation. RESULTS: The factor structure fitted significantly better to the proposed four-factor solution than to a unifactorial solution. However, items 14 (personal relationships), 15 (financial difficulties), and 17 (days off work) consistently showed weak item loading within their factors across all language versions and in both baseline and follow-up datasets. A trimmed SRS (16 non-management items) that used the four least problematic items in each of the four domains yielded better-fitting models across all languages, but equivalence was still not reached. With this shorter version there was equivalence of item loading with respect to treatment (surgery vs conservative), time of assessment (baseline vs 12 months follow-up), and etiology (degenerative vs idiopathic), but not age (< vs ≥50 years). All findings were confirmed in the cross-validation sample. CONCLUSION: We recommend removal of the worst-fitting items from each of the four domains of the SRS-instrument (items 3, 14, 15, 17), together with adaptation and standardization of other items across language versions, to provide an improved version of the instrument with just 16 non-management items.

Allogeneic hematopoietic cell transplantation in intermediate risk acute myeloid leukemia negative for FLT3-ITD, NPM1- or biallelic CEBPA mutations.

BACKGROUND: The value of allogeneic hematopoietic cell transplantation (alloHCT) as postremission treatment is not well defined for patients with intermediate-risk acute myeloid leukemia (AML) without FLT3-ITD, biallelic CEBPA-, or NPM1 mutations (here referred to as NPM1mut-neg/CEBPAdm-neg/FLT3-ITDneg AML) in first complete remission (CR1). PATIENTS AND METHODS: We addressed this question using data from two prospective randomized controlled trials on intensive induction- and risk-stratified postremission therapy. The NPM1mut-neg/CEBPAdm-neg/FLT3-ITDneg AML subgroup comprised 497 patients, aged 18-60 years. RESULTS: In donor versus no-donor analyses, patients with a matched related donor had a longer relapse-free survival (HR 0.5; 95% CI 0.3-0.9, P = 0.02) and a trend toward better overall survival (HR 0.6, 95% CI 0.3-1.1, P = 0.08) compared with patients who received postremission chemotherapy. Notably, only 58% of patients in the donor group were transplanted in CR1. We therefore complemented the donor versus no-donor analysis with multivariable Cox regression analyses, where alloHCT was tested as a time-dependent covariate: overall survival (HR 0.58, 95% CI 0.37-0.9, P = 0.02) and relapse-free survival (HR 0.51, 95% CI 0.34-0.76; P = 0.001) for patients who received alloHCT compared with chemotherapy in CR1 were significantly longer. CONCLUSION: Outside clinical trials, alloHCT should be the preferred postremission treatment of patients with intermediate risk NPM1mut-neg/CEBPAdm-neg/FLT3-ITDneg AML in CR1. CINICALTRIALS.GOV IDENTIFIER: NCT00180115, NCT00180102.

Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification-an approach to classification of patients with t-MDS.

In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p < 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.

Evidence for a role of RUNX1 as recombinase cofactor for TCRß rearrangements and pathological deletions in ETV6-RUNX1 ALL.

T-cell receptor gene beta (TCRß) gene rearrangement represents a complex, tightly regulated molecular mechanism involving excision, deletion and recombination of DNA during T-cell development. RUNX1, a well-known transcription factor for T-cell differentiation, has recently been described to act in addition as a recombinase cofactor for TCRδ gene rearrangements. In this work we employed a RUNX1 knock-out mouse model and demonstrate by deep TCRß sequencing, immunostaining and chromatin immunoprecipitation that RUNX1 binds to the initiation site of TCRß rearrangement and its homozygous inactivation induces severe structural changes of the rearranged TCRß gene, whereas heterozygous inactivation has almost no impact. To compare the mouse model results to the situation in Acute Lymphoblastic Leukemia (ALL) we analyzed TCRß gene rearrangements in T-ALL samples harboring heterozygous Runx1 mutations. Comparable to the Runx1+/- mouse model, heterozygous Runx1 mutations in T-ALL patients displayed no detectable impact on TCRß rearrangements. Furthermore, we reanalyzed published sequence data from recurrent deletion borders of ALL patients carrying an ETV6-RUNX1 translocation. RUNX1 motifs were significantly overrepresented at the deletion ends arguing for a role of RUNX1 in the deletion mechanism. Collectively, our data imply a role of RUNX1 as recombinase cofactor for both physiological and aberrant deletions.

Adolescent's stress responses and psychological functioning when a parent has early breast cancer.

OBJECTIVE: To identify factors associated with psychological functioning in adolescent children of early-stage breast cancer patients. METHOD: Adolescents' self-reported psychological functioning using the Child Behaviour Checklist (YSR), Mental Health subscale of the Child Health Questionnaire (CHQ-MH) and Child Impact of Events (C-IES) scale. The Family Assessment Device (FAD) and the Family Environment Scale (FES cohesion subscale) assessed family functioning. Maternal depression was assessed on the Beck Depression Inventory (BDI) and quality of life using the SF8. Using a cross-sectional within-groups design, assessments were obtained for 56 adolescents of 11-17 years . RESULTS: High rates of stress were found (C-IES) in 33% males and 45% females. Thirty percent of adolescents reported psychological problems (YSR) (28% males and 32% females) when compared with published norms. Poor family functioning was linked with YSR internalising and externalising problems; poor family cohesion with higher externalising and total YSR psychological problems. Maternal depression was linked with adolescent-reported internalising problems. CONCLUSIONS: When mothers have breast cancer, a substantial minority of their adolescent children have psychological and stress response-related problems linked with poor family functioning. These results argue in favour of a family-oriented approach to psychological support of breast cancer patients.

Molecular alterations in bone marrow mesenchymal stromal cells derived from acute myeloid leukemia patients.

The contribution of molecular alterations in bone marrow mesenchymal stromal cells (BM-MSC) to the pathogenesis of acute myeloid leukemia (AML) is poorly understood. Thus we assessed genome-wide genetic, transcriptional and epigenetic alterations in BM-MSC derived from AML patients (AML BM-MSC). Whole-exome sequencing (WES) of AML BM-MSC samples from 21 patients revealed a non-specific pattern of genetic alterations in the stromal compartment. The only mutation present in AML BM-MSC at serial time points of diagnosis, complete remission and relapse was a mutation in the PLEC gene encoding for cytoskeleton key player Plectin in one AML patient. Healthy donor controls did not carry genetic alterations as determined by WES. Transcriptional profiling using RNA sequencing revealed deregulation of proteoglycans and adhesion molecules as well as cytokines in AML BM-MSC. Moreover, KEGG pathway enrichment analysis unravelled deregulated metabolic pathways and endocytosis in both transcriptional and DNA methylation signatures in AML BM-MSC. Taken together, we report molecular alterations in AML BM-MSC suggesting global changes in the AML BM microenvironment. Extended investigations of these altered niche components may contribute to the design of niche-directed therapies in AML.

Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study.

The FLT3 gene is mutated by an internal tandem duplication (ITD) in 20-25% of adults with acute myeloid leukemia (AML). We studied 82 adults <60 years of age with primary AML and normal cytogenetics, who received uniform high-dose therapy and found FLT3 ITD in 23 (28%) patients. When the 23 FLT3 ITD+ cases were compared with the 59 cases with wild-type (WT) FLT3, disease-free survival (DFS) was inferior (P = 0.03), yet overall survival (OS) was not different (P = 0.14). However, 8 (35%) of 23 FLT3 ITD/+ cases also lacked a FLT3 WT allele (FLT3(ITD-R)) as determined by PCR and loss of heterozygosity. Thus, three genotypic groups were identified: normal FLT3(WT/WT), heterozygous FLT3(ITD/WT), and hemizygous FLT3(ITD/-). DFS and OS were significantly inferior for patients with FLT3(ITD/-) (P = 0.0017 and P = 0.0014, respectively). Although DFS and OS for FLT3(WT/WT) and FLT3(ITD/WT) groups did not differ (P = 0.32 and P = 0.98, respectively), OS of the FLT3(ITD/-) group was worse than the FLT3(WT/WT) (P = 0.0005) and FLT3(ITD/WT) (P = 0.008) groups. We propose a model in which FLT3(ITD/-) represents a dominant positive, gain-of-function mutation providing AML cells with a greater growth advantage compared with cells having the FLT3(WT/WT) or FLT3(ITD/WT) genotypes. In conclusion, we have identified the FLT3(ITD/-) genotype as an adverse prognostic factor in de novo AML with normal cytogenetics. A poor prognosis of the relatively young FLT3(ITD/-) adults (median age, 37 years), despite treatment with current dose-intensive regimens, suggests that new treatment modalities, such as therapy with a FLT3 tyrosine kinase inhibitor, are clearly needed for this group of patients.

Silencing of GATA3 defines a novel stem cell-like subgroup of ETP-ALL.

BACKGROUND: GATA3 is pivotal for the development of T lymphocytes. While its effects in later stages of T cell differentiation are well recognized, the role of GATA3 in the generation of early T cell precursors (ETP) has only recently been explored. As aberrant GATA3 mRNA expression has been linked to cancerogenesis, we investigated the role of GATA3 in early T cell precursor acute lymphoblastic leukemia (ETP-ALL). METHODS: We analyzed GATA3 mRNA expression by RT-PCR (n = 182) in adult patients with T-ALL. Of these, we identified 70 of 182 patients with ETP-ALL by immunophenotyping. DNA methylation was assessed genome wide (Illumina Infinium® HumanMethylation450 BeadChip platform) in 12 patients and GATA3-specifically by pyrosequencing in 70 patients with ETP-ALL. The mutational landscape of ETP-ALL with respect to GATA3 expression was investigated in 18 patients and validated by Sanger sequencing in 65 patients with ETP-ALL. Gene expression profiles (Affymetrix Human genome U133 Plus 2.0) of an independent cohort of adult T-ALL (n = 83) were used to identify ETP-ALL and investigate GATA3low and GATA3high expressing T-ALL patients. In addition, the ETP-ALL cell line PER-117 was investigated for cytotoxicity, apoptosis, GATA3 mRNA expression, DNA methylation, and global gene expression before and after treatment with decitabine. RESULTS: In our cohort of 70 ETP-ALL patients, 33 % (23/70) lacked GATA3 expression and were thus defined as GATA3low. DNA methylation analysis revealed a high degree of GATA3 CpG island methylation in GATA3low compared with GATA3high ETP-ALL patients (mean 46 vs. 21 %, p < 0.0001). Genome-wide expression profiling of GATA3low ETP-ALL exhibited enrichment of myeloid/lymphoid progenitor (MLP) and granulocyte/monocyte progenitor (GMP) genes, while T cell-specific signatures were downregulated compared to GATA3high ETP-ALL. Among others, FLT3 expression was upregulated and mutational analyses demonstrated a high rate (79 %) of FLT3 mutations. Hypomethylating agents induced reversal of GATA3 silencing, and gene expression profiling revealed downregulation of hematopoietic stem cell genes and upregulation of T cell differentiation. CONCLUSIONS: We propose GATA3low ETP-ALL as a novel stem cell-like leukemia with implications for the use of myeloid-derived therapies.

Karyotype complexity and prognosis in acute myeloid leukemia.

A complex aberrant karyotype consisting of multiple unrelated cytogenetic abnormalities is associated with poor prognosis in patients with acute myeloid leukemia (AML). The European Leukemia Net classification and the UK Medical Research Council recommendation provide prognostic categories that differ in the definition of unbalanced aberrations as well as the number of single aberrations. The aim of this study on 3526 AML patients was to redefine and validate a cutoff for karyotype complexity in AML with regard to adverse prognosis. Our study demonstrated that (1) patients with a pure hyperdiploid karyotype have an adverse risk irrespective of the number of chromosomal gains, (2) patients with translocation t(9;11)(p21∼22;q23) have an intermediate risk independent of the number of additional aberrations, (3) patients with ⩾4 abnormalities have an adverse risk per se and (4) patients with three aberrations in the absence of abnormalities of strong influence (hyperdiploid karyotype, t(9;11)(p21∼22;q23), CBF-AML, unique adverse-risk aberrations) have borderline intermediate/adverse risk with a reduced overall survival compared with patients with a normal karyotype.

Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia.

DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.

Hematopoietic cell transplantation in patients with intermediate and high-risk AML: results from the randomized Study Alliance Leukemia (SAL) AML 2003 trial.

The optimal timing of allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) is controversial. We report on 1179 patients with a median age of 48 years who were randomized upfront. In the control arm, sibling HCT was scheduled in the first complete remission for intermediate-risk or high-risk AML and matched unrelated HCT in complex karyotype AML. In the experimental arm, matched unrelated HCT in first remission was offered also to patients with an FLT3-ITD (FMS-like tyrosine kinase 3-internal tandem duplication) allelic ratio >0.8, poor day +15 marrow blast clearance and adverse karyotypes. Further, allogeneic HCT was recommended in high-risk AML to be performed in aplasia after induction chemotherapy. In the intent-to-treat (ITT) analysis, superiority of the experimental transplant strategy could not be shown with respect to overall survival (OS) or event-free survival. As-treated analyses suggest a profound effect of allogeneic HCT on OS (HR 0.73; P=0.002) and event-free survival (HR 0.67; P<0.001). In high-risk patients, OS was significantly improved after allogeneic HCT in aplasia (HR 0.64; P=0.046) and after HCT in remission (HR 0.74; P=0.03). Although superiority of one study arm could not be demonstrated in the ITT analysis, secondary analyses suggest that early allogeneic HCT is a promising strategy for patients with high-risk AML.

MDR-1 expression and deletions of chromosomes 7 and 5(Q) separately indicate adverse prognosis in AML.

In order to assess any correlation between MDR-1 expression and chromosomal aberrations, and to define their impact on clinical outcome in newly diagnosed AML pts, we investigated bone marrow and peripheral blood samples of 49 consecutive pts admitted to our hospital. Monosomy 7, trisomy 8 and 5q- were evaluated by means of interphase fluorescence in situ hybridization (FISH). Monosomy 7 was present in 6 pts, trisomy 8 in 5 pts, and 5q- in 6 pts. More than one aberration was seen in 7 pts. Chromosomal aberrations were mostly found in older pts (12/14 >60 years; p=0.03) and in pts with CD34 positive leukemic blasts (13/14 coexpressed CD34, p=0.0004). In 25 pts also standard G-banding analysis was performed leading to concordant results regarding chromosomes 7, 8 and 5. Flow cytometry identifyed MDR-1 positivity (MDR+) in 16 pts. MDR-1 expression appeared to be a characteristic feature in CD34+ AML (12/16 were CD34+ and MDR+ pts; p=0.013). No correlation, however, was found between chromosomal aberrations and MDR-1 expression. Pts with aberrations of either chromosomes 7, 8 or 5 detected by FISH (FISH+) were predominantly resistant to induction therapy (6/8 pts, p=0.004). A lower rate of complete remission (CR) was also seen in pts with MDR-1 expression (p=0.006). MDR+/FISH+ pts (n=3) were all refractory to remission induction, while all MDR-/FISH- pts (n=19) achieved CR (p=0.0006). MDR-1+ as well as pts with aberrations of chromosomes 7, and 5(q) showed a significantly decreased probability of overall survival. In conclusion, MDR-1 expression as well as abnormalities of chromosomes 7, and 5(q) predict poor clinical outcome in AML. The identification of these prognostic factors provides useful information for risk adapted treatment strategies.

Cotrel-Dubousset instrumentation for adolescent idiopathic scoliosis.

We evaluated the results of segmental fixation of the spine with Cotrel-Dubousset instrumentation in ninety-five patients who had adolescent idiopathic scoliosis. The instrumentation was used in an attempt to achieve three-dimensional correction of the scoliosis, maintain lumbar lordosis, create thoracic kyphosis, and avoid the need for a postoperative cast or brace. The patients were followed for twenty-four to sixty-four months (average, thirty-five months). Cotrel-Dubousset instrumentation provided an average correction of the coronal curve of 48 per cent at the time of the most recent follow-up. The normal sagittal curves at the thoracolumbar junction and in the lumbar spine were maintained, and the thoracic kyphosis was increased slightly (average, +7 degrees). Apical translation improved an average of 60 per cent, and apical rotation improved an average of 11 per cent. Forced vital capacity improved an average of 21 per cent, and the one-second forced expiratory volume improved an average of 18 per cent. There were no major neurological deficits. A symptomatic pseudarthrosis developed in one patient. Postoperatively, decompensation of the spine developed in five of the first twenty-six patients who had a Type-II or Type-III curve. This complication was avoided in the last twenty-four patients who had a Type-II or Type-III curve by means of a stricter adherence to the definition of a Type-II curve, and reversal of the bend of the rod and the hooks between the caudal neutral and stable vertebrae. The major advantages of Cotrel-Dubousset instrumentation are the stable fixation that is achieved and the preservation of segmental lumbar lordosis.

Radiographic results of arthrodesis with Cotrel-Dubousset instrumentation for the treatment of adolescent idiopathic scoliosis. A five to ten-year follow-up study.

We evaluated the radiographic results of posterior spinal arthrodesis with use of Cotrel-Dubousset instrumentation in seventy-six patients who had adolescent idiopathic scoliosis. At an average of six years (range, five to ten years) postoperatively, the fusion appeared to be solid in all patients. Comparison of radiographs that had been made immediately postoperatively with those that had been made at the time of the latest follow-up showed that no patient had lost any correction in the coronal plane at the levels with instrumentation and seventy-five had had no change in the thoracic or lumbar sagittal alignment at the levels with or without instrumentation. In the remaining patient, a kyphosis had developed at the junction of the segments with instrumentation and those without instrumentation, necessitating additional operative treatment. Sixty-three patients completed a questionnaire for assessment of the clinical status. Their responses were favorable with regard to function, cosmetic appearance, and general satisfaction with the operative result. Twenty-four (38 per cent) of the sixty-three patients reported occasional pain in the spine that did not interfere with work or school activities. Sixty-two patients stated that, given the hypothetical situation of reverting to the preoperative status, they would have the operation again.

Preventing decompensation in King type II curves treated with Cotrel-Dubousset instrumentation. Strict guidelines for selective thoracic fusion.

Between 1985 and 1988, 50 adolescent idiopathic scoliosis patients with either King Type II (n = 19) or III (n = 31) curves were treated with Cotrel-Dubousset instrumentation and had a minimum of 2-year follow-up. Five of these patients had early postoperative decompensation, and have provided important lessons for the future prevention and treatment of these imbalances. Most problematic was distinguishing between King Type II and double major curve patterns. Proper identification of King Type II curves, which may be successfully treated with selective thoracic fusion, requires careful analysis of the standing preoperative coronal radiograph as well as the side benders. Thus, we now define Type II curves based on the differential between the thoracic and lumbar curve magnitude, apical vertebral deviation from the midline, and apical vertebral rotation on the standing coronal radiograph in addition to a positive flexibility index.

Analysis of pulmonary function and chest cage dimension changes after thoracoplasty in idiopathic scoliosis.

STUDY DESIGN: A prospective study of 19 adolescents and seven adults with idiopathic scoliosis undergoing posterior spinal fusion with segmental spinal instrumentation and a concomitant thoracoplasty had pulmonary function evaluation before surgery and at selected time points up to a minimum 2 years after surgery. OBJECTIVES: The objectives were to determine the effects thoracoplasty had on pulmonary function and chest cage dimension changes at a minimum 2-year follow-up in idiopathic scoliosis patients. SUMMARY OF BACKGROUND DATA: The cosmetic benefits of thoracoplasty on the rib hump deformity are well accepted. The rib resection procedure allowed for procurement of autogenous bone used for the arthrodesis. Short- and long-term pulmonary function evaluation was necessary to determine proper patient selection and any potential sequelae from the rib resection procedure. METHODS: All patients had pulmonary function tests consisting of forced vital capacity, forced expiratory volume in 1 second, and total lung capacity performed before surgery and 3 months, 1 year, and 2 years after surgery. Ten adolescents also had computed tomographic scans before and after surgery to evaluate chest cage dimension changes after the procedure. RESULTS: The 3-month postoperative pulmonary function test values of the 19 adolescents experienced a statistically significant decline, averaging 16% (P < 0.05), however, the mean values for each parameter returned to just slightly below the preoperative value at 2-years follow-up. The pulmonary function test values of the seven adults experienced a 27% initial decline 3 months after surgery and a residual 23% decline 2 years after surgery; both values were statistically significant (P < 0.05). CONCLUSIONS: We reserve the thoracoplasty procedure for adolescents and adults with preoperative pulmonary function values that will tolerate the morbidity associated with the rib resection. Adolescent patients appear to normalize their pulmonary function tests by 2 years follow-up, whereas long-term pulmonary function in the adult patient remains a concern.

Prospective analysis of nutritional status normalization after spinal reconstructive surgery.

STUDY DESIGN: A prospective analysis of nutritional status after surgery in 57 spinal reconstructive surgery patients. OBJECTIVES: To determine the length of time required for patients to return to their preoperative nutritional baseline and to investigate risk factors for patients with prolonged normalization. SUMMARY OF BACKGROUND DATA: The preoperative nutritional status of spinal reconstructive surgery patients appears to be an important parameter of surgical morbidity, complication rates (especially wound healing), patient acceptance, and overall surgical success. METHODS: The nutritional parameters of albumin, pre-albumin, total protein, transferrin, and the absolute lymphocyte count were investigated before surgery and at various time points after surgery. RESULTS: Forty-four patients (Group A) with an average 6.4 fusion levels returned to their preoperative baseline nutritional values by 6 weeks after surgery, whereas 13 patients (Group B) with a statistically increased number of fusion levels of 13.8 (P = 0.0009) took 12 weeks or longer to return to their preoperative baseline. Risk factors for prolonged normalization (Group B) included increased total number of fusion levels, especially 10 or more (P < 0.05); patients undergoing circumferential fusions (P < 0.05); and, to a lesser extent, older patients undergoing multiple fusion levels (P = 0.055). CONCLUSIONS: These data are important when counseling spinal reconstructive surgery patients before surgery and provides information to those patients who may benefit from perioperative nutritional supplementation.

Major intraoperative neurologic deficits in pediatric and adult spinal deformity patients. Incidence and etiology at one institution.

STUDY DESIGN: A retrospective study of 1,090 patients undergoing corrective spinal deformity surgery for scoliosis (n = 920), kyphosis (n = 77), or a combination of the two (n = 93) at one institution. OBJECTIVES: To ascertain the etiologies and incidence of neurologic deficits occurring at the time of surgery. SUMMARY OF BACKGROUND DATA: Potential etiologies of intraoperative neurologic deficits include cord compression, overdistraction, purely vascular, or a combination. METHODS: The study group included only patients with useful function of their lower extremities and normal bowel and bladder control, and patients whose surgeries were in spinal cord territory as opposed to purely cauda equina territory. RESULTS: There were four major neurologic deficits that occurred during surgery. Three of the four deficits were purely vascular in etiology. The fourth may have had a vascular and mechanical etiology. All four patients had anterior and posterior surgery with harvesting of the unilateral convex segmental vessels, and each had a component of hyperkyphosis, as well as intraoperative controlled hypotension. All four patients showed marked improvement of motor weakness with time. CONCLUSIONS: Significant risk factors were combined anterior and posterior surgery (P = 0.009) and hyperkyphosis (P = 0.0006).

Minimum 5-year follow-up of anterior column structural allografts in the thoracic and lumbar spine.

STUDY DESIGN: An analysis of consecutive adult patients treated surgically with anterior column structural allografts for sagittal plane abnormalities. OBJECTIVES: To evaluate the effectiveness of anterior structural allografts in maintaining long-term sagittal plane correction when combined with posterior spinal fusion and posterior segmental spinal instrumentation and to assess anterior allograft incorporation into adjacent vertebral bodies a minimum of 5 years after implantation. SUMMARY OF BACKGROUND DATA: There is no study in the literature in which incorporation and remodeling of anterior column structural allografts with minimum 5-year follow-up are assessed. Do they collapse or resorb or sustain stress fractures between a 2-year and 5-year follow-up? METHODS: Twenty-three consecutive adult patients (mean age, 45 years; range, 25-63 years) had a combination of anterior structural fresh-frozen allograft plus posterior autogenous grafting and posterior segmental spinal instrumentation performed from June 1988 through August 1992. All patients had sagittal plane abnormalities, and all surgeries were performed by the same surgeon. Twenty of the 23 patients returned for follow-up examinations for at least 5 years (average, 7 +/- 3 years; range, 5 +/- 4-10 +/- 3 years). Diagnoses included kyphoscoliosis (n = 8), spondylolisthesis (n = 3), degenerative disc disease (n = 3), and acute or chronic fracture (n = 6). The allografts spanned only disc spaces in 16 patients, and vertebral bodies and disc spaces in 4 patients. Forty disc spaces and four vertebral bodies were grafted, and 67 structural allografts were placed. Upright radiographs were analyzed before surgery, immediately after surgery, and at final follow-up examination to assess the degree of anterior allograft incorporation and maintenance of sagittal correction. A strict 4-point grading system was used. Two independent observers, not involved with surgical procedures, analyzed the radiographic results. RESULTS: Of the 67 structural allografts, 66 (98.5%) showed incorporation. Both observers concluded that none of the 67 structural allografts showed evidence of collapse. In all grafted levels and in any patient, there was no difference in sagittal plane measurements obtained immediately after surgery and those obtained at follow-up examinations 2 years and 5 or more years after surgery. CONCLUSIONS: Anterior fresh-frozen structural allograft works effectively in the long term to maintain correction of sagittal plane abnormalities if combined with posterior fusion and instrumentation. A minimum of 5 years after surgery, there is a high rate of structural allograft incorporation into the adjacent vertebral bodies.