Is MMTV associated with human breast cancer? Maybe, but probably not.

BACKGROUND: Conflicting results regarding the association of MMTV with human breast cancer have been reported. Published sequence data have indicated unique MMTV strains in some human samples. However, concerns regarding contamination as a cause of false positive results have persisted. METHODS: We performed PCR assays for MMTV on human breast cancer cell lines and fresh frozen and formalin fixed normal and malignant human breast epithelial samples. Assays were also performed on peripheral blood mononuclear cells from volunteer blood donors and subjects at risk for human retroviral infections. In addition, assays were performed on DNA samples from wild and laboratory mice. Sequencing of MMTV positive samples from both humans and mice were performed and phylogenetically compared. RESULTS: Using PCR under rigorous conditions to prevent and detect "carryover" contamination, we did detect MMTV DNA in human samples, including breast cancer. However, the results were not consistent and seemed to be an artifact. Further, experiments indicated that the probable source of false positives was murine DNA, containing endogenous MMTV, present in our building. However, comparison of published and, herein, newly described MMTV sequences with published data, indicates that there are some very unique human MMTV sequences in the literature. CONCLUSION: While we could not confirm the true presence of MMTV in our human breast cancer subjects, the data indicate that further, perhaps more traditional, retroviral studies are warranted to ascertain whether MMTV might rarely be the cause of human breast cancer.

Delayed Seroconversion to HTLV-II Is Associated with a Stop-Codon Mutation in the pol Gene.

A known HIV-1-positive intravenous drug user was found to be human T cell lymphoma/leukemia virus-II (HTLV-II) DNA positive by polymerase chain reaction but seronegative in a screening ELISA. He was consistently DNA positive but took 2 years to fully seroconvert. Sequencing of the HTLV-II strain in his cultured T lymphocytes indicated that it is a prototypical type A strain with no major differences in the long terminal repeat DNA sequence, nor major amino acid differences in the Gag, Env, Tax, and Rex proteins. However, a mutation in its pol gene created a stop codon at amino acid 543 of the Pol protein, a region that encodes for the RNase function. This mutation may account for the subject's slow seroconversion.

Exploring Novel Medicare Readmission Risk Variables in Chronic Obstructive Pulmonary Disease Patients at High Risk of Readmission within 30 Days of Hospital Discharge.

RATIONALE: New risk factors for readmission within 30 days of hospital discharge for patients with chronic obstructive pulmonary disease (COPD) need to be identified in view of the lack of efficacy of current interventions for preventing readmission. OBJECTIVES: To identify novel risk predictors for 30-day readmission among COPD index admissions at high risk of readmission. METHODS: For this analysis, we used the fiscal year 2015 hospital-specific Medicare Hospital Readmissions Reduction Program workbook for Staten Island University Hospital (Staten Island, NY). We analyzed 41 variables, each with a risk-variable score. A predicted probability of readmission was calculated for each case by using the risk-variable regression coefficient and a hospital-specific effect. A predicted probability greater than 0.4 was used to identify patients with COPD with a high risk of readmission in both the readmitted and nonreadmitted groups. A percent ratio of the readmission percentage divided by the nonreadmission percentage was generated for each risk variable for patients with a predicted probability of readmission greater than 0.4. A percent ratio greater than 3 was used to identify high-risk variables predictive of readmission. A risk index was defined as the number of high-risk variables present for each index admission. MEASUREMENTS AND MAIN RESULTS: Nine high-risk variables were identified. A risk index greater than 3 for all index admissions identified 54 (22.7%) of 238 readmitted patients versus 41 (6.5%) of 630 nonreadmitted patients (P < 0.0001; positive predictive value, 0.56; specificity, 0.93). A risk index greater than 2 for multiple-admission patients identified 56 (65.1%) of 86 readmitted patients versus 135 (40.7%) of 332 nonreadmitted patients (P < 0.0001; positive predictive value, 0.65; specificity, 0.86). Over 30% of readmitted patients meeting the risk index criteria were discharged to home without organized home care. Sleep apnea, vertebral fractures, and electrolyte and acid-base disorders were newly identified predictors of readmission. CONCLUSIONS: This study developed a risk index based upon the 2015 Hospital Readmissions Reduction Program worksheet for one hospital to explore risk variables predictive of 30-day readmissions for patients with COPD at high risk of readmission (>0.4). Because most currently used interventions lack efficacy in preventing 30-day readmission, interventions based upon the newly identified variables should be validated with larger validation cohorts.

Which Variables Are Associated With Patient-reported Outcomes After Discectomy? Review of SPORT Disc Herniation Studies.

BACKGROUND: The Spine Patient Outcomes Research Trial (SPORT) evaluated the effects of surgery versus nonoperative treatment for lumbar intervertebral disc herniation (IDH), among other pathologies. Multiple subgroup analyses have been completed since the initial publications, which have further defined which patient factors lead to better or worse patient-reported outcomes; however, the degree to which these factors influence patient-reported outcomes has not been explored. QUESTIONS/PURPOSES: We reviewed the subgroup analyses of the SPORT IDH studies to answer the following questions: (1) What factors predicted improvement in patient-reported outcomes after operative or nonoperative treatment of lumbar IDH? (2) What factors predicted worse patient-reported outcomes compared to baseline after operative or nonoperative treatment of lumbar IDH? And (3) what factors influenced patient-reported outcomes of surgery in patients with lumbar IDH? METHODS: We conducted a MEDLINE(®) search to identify the subgroup analyses of the SPORT IDH data that were responsive to our study questions. Eleven articles were identified that met our search criteria. RESULTS: The patient factors associated with larger improvements in Oswestry Disability Index at 4 years with either surgical or nonoperative treatment included a higher baseline Oswestry Disability Index, BMI of less than 30, not being depressed, being insured, having no litigation pending, not having workers compensation, and having symptoms for less than 6 weeks, though there were others. Factors leading to improvement with surgical treatment were mostly related to anatomic characteristics of the disc herniation such as posterolateral and sequestered herniations. There were no patient or clinical factors identified that were associated with worse patient-reported outcomes compared to baseline after either operative or nonoperative treatment. At 2-year followup, the treatment effects were greater for those patients with upper-level herniations, patients not receiving workers compensation, and nondiabetic patients. In a 4-year multivariate analysis, being married, without joint problems, and having worse symptoms at baseline resulted in greater treatment effect with surgery. CONCLUSIONS: While most patients with IDH will likely see improvement with either surgical or nonoperative treatment, there are patient-related factors that can help predict which subgroups will demonstrate a greater improvement with surgery, such as not having joint problems, being married, having worsening symptoms at baseline, and not having diabetes. These results can help providers and patients when discussing treatment options. LEVEL OF EVIDENCE: Level I, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Increased seroreactivity to human T cell lymphoma/leukemia virus-related endogenous sequence-1 Gag peptides in patients with human T cell lymphoma/leukemia virus myelopathy.

Previously, we had shown that although only 8% of patients with large granular lymphocytic leukemia (LGLL) were infected with human T cell lymphoma/leukemia virus (HTLV)-2, almost half had antibodies to HTLV Gag and Env peptides. Herein, we investigated whether this could be due to cross-reactive antibodies to two homologous peptides in the Gag protein of the endogenous retrovirus HTLV-related endogenous sequence-1 (HRES-1). In addition, we had previously shown that patients with HTLV neurodegenerative diseases had increased seroreactivity to homologous HERV-K10 endogenous retrovirus peptides. Hence, in this study we also examined whether these patients had increased seroreactivity to the aforementioned HRES-1 Gag peptides. Sera from 100 volunteer blood donors (VBD), 53 patients with LGLL, 74 subjects with HTLV-1 or 2 infection (58 nonmyelopathy and 16 myelopathy), and 83 patients with multiple sclerosis (MS) were evaluated. The HTLV-positive myelopathy (HAM) patients had a statistically increased prevalence of antibodies to both HRES-1 Gag peptides (81%) vs. the VBD (0%), LGLL patients (13%), and MS patients (1%), and the HTLV-positive nonmyelopathy subjects (21%). The data suggest that cross-reactivity to HRES-1 peptides could be involved in the pathogenesis of HAM. The difference between the VBD and LGLL patients was also statistically significant, also suggesting a possible association in a minority of patients.

Increased seroreactivity to HERV-K10 peptides in patients with HTLV myelopathy.

BACKGROUND: Previously, we had shown that persons infected with human T-cell lymphoma leukemia virus 1 or 2 (HTLV-1 or 2) had an increased prevalence of antibodies to a peptide in the Pol protein of the retrovirus HERV-K10, homologous to a peptide in HTLV gp21 envelope protein. The prevalence rate was higher in those with myelopathy vs. non-myelopathy. We have now extended our observations to a cohort restricted to North America in whom the diagnosis of HTLV myelopathy was rigorously confirmed to also test for reactivity to another HERV-K10 peptide homologous to the HTLV p24 Gag protein. METHODS: Sera from 100 volunteer blood donors (VBD), 53 patients with large granular lymphocytic leukemia (LGLL), 74 subjects with HTLV-1 or 2 infection (58 non-myelopathy and 16 myelopathy) and 83 patients with multiple sclerosis (MS) were evaluated in ELISA assays using the above peptides. RESULTS: The HTLV myelopathy patients had a statistically significant increased prevalence of antibodies to both HERV-K10 peptides (87.5%) vs. the VBD (0%), LGLL patients (0%), MS patients (4.8%), and the HTLV positive non-myelopathy subjects (5.2%). CONCLUSION: The data suggest that immuno-cross-reactivity to HERV-K10 peptides and/or transactivation of HERV-K10 expression by the HTLV Tax protein may be involved in the pathogenesis of HTLV-associated myelopathy/tropical spastic paraparesis and spastic ataxia.

LGL leukemia and HTLV.

Samples were obtained from 53 large granular lymphocytic leukemia (LGLL) patients and 10,000 volunteer blood donors (VBD). Sera were screened in an HTLV-1 enzyme immunoassay (EIA) and further analyzed in peptide-specific Western blots (WB). DNAs were analyzed by HTLV-1, -2, -3, and -4-specific PCR. Forty four percent of LGLL patients vs. 0.12 % of VBD had anti-HTLV antibodies via EIA (p < 0.001). WB and PCR revealed that four LGLL patients (7.5%) vs. one VBD patient (0.01%) were infected with HTLV-2 (p < 0.001), suggesting an HTLV-2 etiology in a minority of cases. No LGLL patient was positive for HTLV-1, -3, or -4, whereas only one EIA-positive VBD was positive for HTLV-1 and none for HTLV-3 or -4. The HTLV EIA-positive, PCR-negative LGLL patients' sera reacted to epitopes within HTLV p24 gag and gp21 env. Other then the PTLV/BLV viruses, human endogenous retroviral element HERV K10 was the only sequence homologous to these two HTLV peptides, raising the possibility of cross-reactivity. Although three LGLL patients (5.7%) vs. none of 110 VBD patients tested positive for antibodies to the homologous HERV K10 peptide (p = 0.03), the significance of the anti-HTLV seroreactivity observed in many LGLL patients remains unclear. Interestingly, out of 36 HTLV-1-positive control subjects, 3 (8%) (p = 0.014) were positive for antibodies to HERV K10; all three had myelopathy. Out of 64 HTLV-2-positive control subjects 16 (25%) (p = <0.001) were positive for HERV K10 antibodies, and 4 (6%) of these had myelopathy. Out of 22 subjects with either HTLV-1 or -2 myelopathy, 7 (31.8%) were positive for HERV K10 antibodies, and out of 72 HTLV-infected subjects without myelopathy, 12 (16.7%) were positive for anti-HERV K10 antibodies (p = 0.11). The prevalence of anti-HERV K10 antibodies in these populations and the clinical implications thereof need to be pursued further.

Nonhemolytic, nonmotile gram-positive rods indicative of Bacillus anthracis.

We report a 40-year-old female patient who was admitted to the hospital because of a left ovarian mass torsion. A nonhemolytic, nonmotile Bacillus, suspicious of Bacillus anthracis, was isolated from a blood culture. We discuss the evaluation that led to the final identification of the bacterium as B. megaterium.