Analysis of complications and revisions after spine surgery in 270 multiple myeloma patients with spinal involvement.

BACKGROUND CONTEXT: Patients with multiple myeloma (MM) are at increased risk of infections and suffer from poor bone quality due to their disseminated malignant bone disease. Therefore, postoperative complications may occur following surgical treatment of MM lesions. PURPOSE: In this study, we aimed to determine the incidence of postoperative complications and retreatments after spinal surgery in MM patients. Additionally, we sought to identify risk factors associated with complications and retreatments. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: In total, 270 patients with MM who received surgical treatment for spinal involvement between 2008 and 2021 were included. OUTCOME MEASURES: The incidence of perioperative complications within 6 weeks and reoperations within 2.5 years and individual odds ratios for factors associated with these complications and reoperations. METHODS: Data were collected through manual chart review. Hosmer and Lemeshow's purposeful regression method was used to identify risk factors for complications and reoperations. RESULTS: The median age of our cohort was 65 years (SD = 10.8), and 58% were male (n = 57). Intraoperative complications were present in 24 patients (8.9%). The overall 6-week complication rate after surgery was 35% (n = 95). The following variables were independently associated with 6-week complications: higher Genant grading of a present vertebral fracture (OR 1.41; 95% CI 1.04-1.95; p = .031), receiving intramuscular or intravenous steroids within a week prior to surgery (OR 3.97; 95% CI 1.79-9.06; p = .001), decompression surgery without fusion (OR 6.53; 95% CI 1.30-36.86; p = .026), higher creatinine levels (OR 2.18; 95% CI 1.19-5.60; p = .014), and lower calcium levels (OR 0.58; 95% CI 0.37-0.88; p = .013). A secondary surgery was indicated for 53 patients (20%), of which 13 (4.8%) took place within two weeks after the initial surgery. We additionally discovered factors associated with retreatments, which are elucidated within the manuscript. CONCLUSION: The goal of surgical treatment for MM bone disease is to enhance patient quality of life and reduce symptom burden. However, postoperative complication rates remain relatively high after spine surgery in patients with MM, likely attributable to both inherent characteristics of the disease and patient comorbidities. The risk for complications and secondary surgeries should be explored and a multidisciplinary approach is crucial.

Neurologic Outcomes After Radiation Therapy for Severe Spinal Cord Compression in Multiple Myeloma: A Study of 162 Patients.

BACKGROUND: Bone destruction is the most frequent disease-defining clinical feature of multiple myeloma (MM), resulting in skeletal-related events such as back pain, pathological fractures, or neurologic compromise including epidural spinal cord compression (ESCC). Up to 24% of patients with MM will be affected by ESCC. Radiation therapy has been proven to be highly effective in pain relief in patients with MM. However, a critical knowledge gap remains with regard to neurologic outcomes in patients with high-grade ESCC treated with radiation. METHODS: We retrospectively included 162 patients with MM and high-grade ESCC (grade 2 or 3) who underwent radiation therapy of the spine between January 2010 and July 2021. The primary outcome was the American Spinal Injury Association (ASIA) score after 12 to 24 months, or the last known ASIA score if the patient had had a repeat treatment or died. Multivariable logistic regression was used to assess factors associated with poor neurologic outcomes after radiation, defined as neurologic deterioration or lack of improvement. RESULTS: After radiation therapy, 34 patients (21%) had no improvement in their impaired neurologic function and 27 (17%) deteriorated neurologically. Thirty-six patients (22%) underwent either surgery or repeat irradiation after the initial radiation therapy. There were 100 patients who were neurologically intact at baseline (ASIA score of E), of whom 16 (16%) had neurologic deterioration. Four variables were independently associated with poor neurologic outcomes: baseline ASIA (odds ratio [OR] = 6.50; 95% confidence interval [CI] = 2.70 to 17.38; p < 0.001), Eastern Cooperative Oncology Group (ECOG) performance status (OR = 6.19; 95% CI = 1.49 to 29.49; p = 0.015), number of levels affected by ESCC (OR = 4.02; 95% CI = 1.19 to 14.18; p = 0.026), and receiving steroids prior to radiation (OR = 4.42; 95% CI = 1.41 to 16.10; p = 0.015). CONCLUSIONS: Our study showed that 38% of patients deteriorated or did not improve neurologically after radiation therapy for high-grade ESCC. The results highlight the need for multidisciplinary input and efforts in the treatment of high-grade ESCC in patients with MM. Future studies will help to improve patient selection for specific and standardized treatments and to clearly delineate which patients are likely to benefit from radiation therapy. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

The effects of homelessness on Veterans' health care service use: an evaluation of independence from comorbidities.

OBJECTIVES: This study evaluates the prevalence of Multiple Comorbid Chronic Disease (MCCD) within homeless and non-homeless Veterans and the association between MCCD and inpatient medical care. METHODS: All individuals seen in the VA North Texas Health Care System between October 1, 2009 and September 30, 2010 (n = 102,034) were evaluated. Homelessness during the year and the number of common chronic diseases were evaluated for an association with likelihood of medical and psychiatric hospitalizations, bed days of care, inpatient substance treatment, rehabilitation admissions, and emergency department visits. RESULTS: Homeless Veterans had higher all-cause mortality rates and rates of use of almost all resources after controlling for chronic disease burden using the Charlson Comorbidity Index, psychiatric illnesses, substance use disorders, and demographic variables. CONCLUSIONS: Homelessness Veterans are vulnerable to a high use of resources and mortality, independent of medical and psychiatric conditions. This finding should focus additional attention on reducing homelessness.

Quantitative trait loci for live animal and carcass composition traits in Jersey and Limousin back-cross cattle finished on pasture or feedlot.

A quantitative trait locus (QTL) study was carried out in two countries, recording live animal and carcass composition traits. Back-cross calves (385 heifers and 398 steers) were generated, with Jersey and Limousin breed backgrounds. The New Zealand cattle were reared on pasture to carcass weights averaging 229 kg, whilst the Australian cattle were reared on grass and finished on grain (for at least 180 days) to carcass weights averaging 335 kg. From 11 live animal traits and 31 carcass composition traits respectively, 5 and 22 QTL were detected in combined-sire analyses, which were significant (P < 0.05) on a genome-wise basis. Fourteen significant traits for carcass composition QTL were on chromosome 2 and these were traits associated with muscling and fatness. This chromosome carried a variant myostatin allele (F94L), segregating from the Limousin ancestry. Despite very different cattle management systems between the two countries, the two populations had a large number of QTL in common. Of the 18 traits which were common to both countries, and which had significant QTL at the genome-wise level, eight were significant in both countries.

A genome-screen experiment to detect quantitative trait loci affecting resistance to facial eczema disease in sheep.

Facial eczema (FE) is a secondary photosensitization disease arising from liver cirrhosis caused by the mycotoxin sporidesmin. The disease affects sheep, cattle, deer and goats, and costs the New Zealand sheep industry alone an estimated NZ$63M annually. A long-term sustainable solution to this century-old FE problem is to breed for disease-resistant animals by marker-assisted selection. As a step towards finding a diagnostic DNA test for FE sensitivity, we have conducted a genome-scan experiment to screen for quantitative trait loci (QTL) affecting this trait in Romney sheep. Four F(1) sires, obtained from reciprocal matings of FE resistant and susceptible selection-line animals, were used to generate four outcross families. The resulting half-sib progeny were artificially challenged with sporidesmin to phenotype their FE traits measured in terms of their serum levels of liver-specific enzymes, namely gamma-glutamyl transferase and glutamate dehydrogenase. In a primary screen using selective genotyping on extreme progeny of each family, a total of 244 DNA markers uniformly distributed over all 26 ovine autosomes (with an autosomal genome coverage of 79-91%) were tested for linkage to the FE traits. Data were analysed using Haley-Knott regression. The primary screen detected one significant and one suggestive QTL on chromosomes 3 and 8 respectively. Both the significant and suggestive QTL were followed up in a secondary screen where all progeny were genotyped and analysed; the QTL on chromosome 3 was significant in this analysis.

Identifying genes for intestinal nematode resistance using transcriptional profiling.

Gene expression was compared between resistant and susceptible Perendale lambs that had either never been exposed to gastrointestinal nematode challenge (had a naïve immune system with respect to parasites) or had been naturally challenged on pasture with nematodes. Only a small number of genes were differentially expressed between the naive resistant and susceptible animals, but many genes were differentially expressed between the resistant and susceptible challenged animals. The differentially expressed genes were involved in a variety of biological processes, most notably the immune response, the stress response and gene regulation via chromatin remodelling. The transcriptional profiling experiments also detected gene expression differences in the Ovar-DQA1 gene between resistant and susceptible challenged animals. A null allele of this gene was demonstrated to be associated with susceptibility to gastrointestinal parasites in some, but not all populations. This allele is not thought to be causal for susceptibility.

The constituents of Microctonus sp. parasitoid venoms.

Purified RNA transcripts from venom glands dissected from the parasitoid wasp Microctonus hyperodae were copied, cloned and sequenced using traditional dideoxy sequencing methods. Using mass spectrometry analysis of the trypsinised PAGE gel protein bands we identified the RNA transcripts for the 3 most abundant proteins found in the venom and hence obtained their full protein sequence. Other abundant transcripts were also further sequenced. To reduce the effort required to obtain transcript information we dissected venom glands from a second parasitoid, Microctonus aethiopoides (Morocco biotype). The RNA transcripts were purified and reverse transcribed but instead of cloning the cDNA it was directly sequenced using Roche GS20 pyrosequencing. Results from a single GS20 sequencing run provided data similar to that obtained by the traditional methods used in analysing transcripts from M. hyperodae in a fraction of the time and cost. Comparing the transcripts between the two species showed that a similar range of genes are expressed with the putative orthologs of seven of the eight full length genes characterised from M. hyperodae being found in M. aethiopoides. Pyrosequencing should provide a valuable new method for rapidly sampling transcripts from a wide range of specialised insect tissues.

Effect of myostatin F94L on carcass yield in cattle.

In this study, a highly significant quantitative trait locus (QTL) for meat percentage, eye muscle area (EMA) and silverside percentage was found on cattle chromosome 2 at 0-15 cM, a region containing the positional candidate gene growth differentiation factor 8 (GDF8), which has the common alias myostatin (MSTN). Loss-of-function mutations in the MSTN gene are known to cause an extreme 'double muscling' phenotype in cattle. In this study, highly significant associations of MSTN with cattle carcass traits were found using maternally inherited MSTN haplotypes from outbred Limousin and Jersey cattle in a linkage disequilibrium analysis. A previously reported transversion in MSTN (AF320998.1:g.433C>A), resulting in the amino acid substitution of phenylalanine by leucine at position 94 of the protein sequence (F94L), was the only polymorphism consistently related to increased muscling. Overall, the size of the g.433C>A additive effect on carcass traits was moderately large, with the g.433A allele found to be associated with a 5.5% increase in silverside percentage and EMA and a 2.3% increase in total meat percentage relative to the g.433C allele. The phenotypic effects of the g.433A allele were partially recessive. This study provides strong evidence that a MSTN genotype can produce an intermediate, non-double muscling phenotype, which should be of significant value for beef cattle producers.

Genomic analysis of Oryctes rhinoceros virus reveals genetic relatedness to Heliothis zea virus 1.

Oryctes rhinoceros virus (OrV) is an unassigned invertebrate dsDNA virus with enveloped and rod-shaped virions. Two cloned PstI fragments, C and D, of OrV DNA have been sequenced, consisting of 19,805 and 17,146 bp, respectively, and comprising about 30% of the OrV genome. For each of the two fragments, 20 open reading frames (ORFs) of 150 nucleotides or greater with no or minimal overlap were predicted. Ten of the predicted 40 ORFs revealed significant similarities to Heliothis zea virus 1 (HzV-1) ORFs, of which five, lef-4, lef-5, pif-2, dnapol and ac81, are homologues of conserved core genes in the family Baculoviridae, and one is homologous to baculovirus rr1. A baculovirus odv-e66 homologue is also present in OrV. Five ORFs encode proteins homologous to cellular thymidylate synthase (TS), patatin-like phospholipase, mitochondrial carrier protein, Ser/Thr protein phosphatase, and serine protease, respectively. TS is phylogenetically related to those of eukarya and nucleo-cytoplasmic large dsDNA viruses. However, the remaining 25 ORFs have poor or no sequence matches with the current databases. Both the gene content of the sequenced fragments and the phylogenetic analyses of the viral DNA polymerase suggest that OrV is most closely related to HzV-1. These findings and the re-evaluation of the relationship of HzV-1 to baculoviruses suggest that a new virus genus, Nudivirus, should be established, containing OrV and HzV-1, which are genetically related to members of the family Baculoviridae.

The use of genetic modification technologies in the discovery of genes affecting production traits and disease resistance in animals.

Genetic modification technologies, developed initially in laboratory strains of selected bacteria and viruses, are essential tools for understanding the genomes of livestock. These tools allow researchers to: isolate, sequence and characterise any livestock gene; locate genes on chromosomes; follow the inheritance of any gene and/or chromosomal region in any pedigree; detect phenotypic variation due to, or associated with, variation in the DNA sequence of a gene and identify the genetic alteration causing this. Most of the many thousands of genes identified in livestock vary between individuals. Finding the best type of the key genes affecting animal productivity is an exciting and a daunting task. It is only possible with the use of laboratory-based genetic modification techniques. This review will briefly describe the technologies now in use and, using local examples, show how molecular geneticists are using these to help identify genetic alterations and breed healthier or more productive animals. As with any new technology, a new language evolves to describe new products and processes. The new language makes communication easier between participants in the field but more difficult for others to understand the technology. A glossary of terms has therefore been added to this review to help readers less familiar with molecular genetics.

Linkage disequilibrium in domestic sheep.

The last decade has seen a dramatic increase in the number of livestock QTL mapping studies. The next challenge awaiting livestock geneticists is to determine the actual genes responsible for variation of economically important traits. With the advent of high density single nucleotide polymorphism (SNP) maps, it may be possible to fine map genes by exploiting linkage disequilibrium between genes of interest and adjacent markers. However, the extent of linkage disequilibrium (LD) is generally unknown for livestock populations. In this article microsatellite genotype data are used to assess the extent of LD in two populations of domestic sheep. High levels of LD were found to extend for tens of centimorgans and declined as a function of marker distance. However, LD was also frequently observed between unlinked markers. The prospects for LD mapping in livestock appear encouraging provided that type I error can be minimized. Properties of the multiallelic LD coefficient D' were also explored. D' was found to be significantly related to marker heterozygosity, although the relationship did not appear to unduly influence the overall conclusions. Of potentially greater concern was the observation that D' may be skewed when rare alleles are present. It is recommended that the statistical significance of LD is used in conjunction with coefficients such as D' to determine the true extent of LD.

Evaluation of single-nucleotide polymorphisms in CAPN1 for association with meat tenderness in cattle.

Micromolar calcium activated neutral protease (CAPN1) was evaluated as a candidate gene for a quantitative trait locus (QTL) on BTA29 affecting meat tenderness by characterization of nucleotide sequence variation in the gene. Single-nucleotide polymorphisms (SNP) were identified by sequencing all 22 exons and 19 of the 21 introns in two sires (Piedmontese x Angus located at the U.S. Meat Animal Research Center in Clay Center, NE; Jersey x Limousin located at AgResearch in New Zealand) of independent resource populations previously shown to be segregating meat tenderness QTL on BTA29. The majority of the 38 SNP were found in introns or were synonymous substitutions in the coding regions, with two exceptions. Exons 14 and 9 contained SNP that were predicted to alter the protein sequence by the substitution of isoleucine for valine in Domain III of the protein, and alanine for glycine in Domain II of the protein. The resource populations were genotyped for these two SNP in addition to six intronic polymorphisms and two silent substitutions. Analysis of genotypes and shear force values in both populations revealed a difference between paternal CAPN1 alleles in which the allele encoding isoleucine at position 530 and glycine at position 316 associated with decreased meat tenderness (increased shear force values) relative to the allele encoding valine at position 530 and alanine at position 316 (P < 0.05). The association of maternal alleles with meat tenderness phenotypes is consistent with the hypothesis of CAPN1 as the gene underlying the QTL effect in two independent resource populations and presents the possibility of using these markers for selective breeding to reduce the numbers of animals with unfavorable meat tenderness traits.

Familial predictors of treatment outcome in childhood anxiety disorders.

OBJECTIVE: To determine whether family factors are predictive of outcome in children with anxiety disorders who are receiving cognitive-behavioral treatment. METHOD: Participants were 61 children aged 8 to 12 years (mean = 10.0, SD = 1.4) with Axis I anxiety disorders who had been referred to a large Toronto children's hospital. Parents and children completed measures assessing family functioning, parenting stress, parental frustration, and parental psychopathology before and after treatment. Outcome measures included clinician-rated functioning (Children's Global Assessment Scale) and self- and parent-rated anxiety (Revised Children's Manifest Anxiety Scale). RESULTS: Child ratings of family dysfunction and frustration predicted clinician-rated improvement (total R2 = 0.28, p < .001). Mother and father reports of family dysfunction, and maternal parenting stress, predicted mother-rated child improvement (total R2 = 0.18, p < .01). Father-rated somatization and child reports of family dysfunction and frustration predicted child-rated improvement (total R2 = 0.25, p < .001). Several family factors improved with treatment. CONCLUSION: Family dysfunction appears to be related to less favorable treatment outcome in children with anxiety disorders.