A systematic review of prognostic factors predicting survival in patients with spinal bone metastases.

PURPOSE: For the selection of treatment in patients with spinal bone metastases (SBM), survival estimation plays a crucial role to avoid over- and under-treatment. To aid clinicians in this difficult task, several prediction models have been developed, consisting of many different risk factors. The aim of this systematic review was to identify prognostic factors that are associated with survival in patients with SBM to support development of predictive models. METHODS: A systematic review was performed with focus on prognostic factors associated with survival in patients with SBM. Two reviewers independently selected studies for inclusion and assessed the risk of bias. A level of evidence synthesis was performed for each prognostic factor. Inter-observer agreement for the risk of bias assessment was determined by the kappa-statistic. RESULTS: After screening, 142 full-text articles were obtained, of which 22 met the eligibility criteria. A total of 43 different prognostic factors were investigated in the included studies, of which 17 were relevant to pre-treatment survival estimation. The prognostic factors most frequently associated with survival were the primary tumor and the performance status. The prognostic factors most frequently not associated with survival were age, gender, number and location of the SBM and the presence of a pathologic fracture. CONCLUSIONS: Prognostication for patients with SBM should be based on an accurate primary tumor classification, combined with a performance score. The benefit of adding other prognostic factors is doubtful.

Thrombin-activatable fibrinolysis inhibitor in human abdominal aortic aneurysm disease.

Essentials Patients with abdominal aortic aneurysms (AAA) develop dense clots that are resistant to lysis. This study explores the role of thrombin-activatable fibrinolysis inhibitor (TAFI) in human AAA. There is evidence of chronically increased TAFI activation in patients with AAA. TAFI may represent a pharmacological target for cardiovascular risk reduction in AAA. SUMMARY: Background Intra-luminal thrombosis is a key factor in growth of abdominal aortic aneurysms (AAAs). Patients with AAA form dense clots that are resistant to fibrinolysis. Thrombin-activatable fibrinolysis inhibitor (TAFI) has been shown to influence AAA development in murine models. Objective The aim of this study is to characterize the role of TAFI in human AAA. Methods Plasma levels of TAFI, TAFI activation peptide (TAFI-AP), activated/inactivated TAFI (TAFIa/ai) and plasmin-α2-antiplasmin complex were measured by ELISAs in patients with AAA (n = 202) and controls (n = 188). Results TAFIa/ai and TAFI-AP levels were higher in patients than controls (median [IQR], 20.3 [14.6-32.8] ng mL-1 vs. 14.2 [11.2-19.3] ng mL-1 and 355.0 [232.4-528.1] ng mL-1 vs. 248.6 [197.1-328.1] ng mL-1 ). TAFIa/ai was positively correlated with TAFI-AP (r = 0.164). Intact TAFI levels were not different between patients and controls (13.4 [11.2-16.1] µg mL-1 vs. 12.8 [10.6-15.4] µg mL-1 ). Plasmin-α2-antiplasmin was higher in AAA patients than controls (690.0 [489.1-924.3] ng mL-1 vs. 480.7 [392.6-555.3] ng mL-1 ). Conclusions The increase in TAFIa/ai and TAFI-AP suggests an increased TAFI activation in patients with AAA. Prospective studies are required to further elucidate the role of TAFI and fibrinolysis in AAA pathogenesis.

Epidermal growth factor receptor mutations should be considered as a prognostic factor for survival of patients with pathological fractures or painful bone metastases from non-small cell lung cancer.

AIMS: This study aims to assess first, whether mutations in the epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (kRAS) genes are associated with overall survival (OS) in patients who present with symptomatic bone metastases from non-small cell lung cancer (NSCLC) and secondly, whether mutation status should be incorporated into prognostic models that are used when deciding on the appropriate palliative treatment for symptomatic bone metastases. PATIENTS AND METHODS: We studied 139 patients with NSCLC treated between 2007 and 2014 for symptomatic bone metastases and whose mutation status was known. The association between mutation status and overall survival was analysed and the results applied to a recently published prognostic model to determine whether including the mutation status would improve its discriminatory power. RESULTS: The median OS was 3.9 months (95% confidence interval (CI) 2.1 to 5.7). Patients with EGFR (15%) or kRAS mutations (34%) had a median OS of 17.3 months (95% CI 12.7 to 22.0) and 1.8 months (95% CI 1.0 to 2.7), respectively. Compared with EGFR-positive patients, EGFR-negative patients had a 2.5 times higher risk of death (95% CI 1.5 to 4.2). Incorporating EGFR mutation status in the prognostic model improved its discriminatory power. CONCLUSION: Survival prediction models for patients with symptomatic bone metastases are used to determine the most appropriate (surgical) treatment for painful or fractured lesions. This study shows that NSCLC should not be regarded as a single entity in such models. Cite this article: Bone Joint J 2017;99-B:516-21.

Secondary traumatic stress and secondary posttraumatic growth in a sample of Dutch police family liaison officers.

This study investigated secondary traumatic stress (STS) and secondary posttraumatic growth (SPG) in a sample of Dutch police family liaison officers (N = 224). Our study had two aims: (a) to identify potential risk and protective factors for STS and (b) to investigate the association between STS and SPG. None of the risk (caseload and a personal trauma history) and protective factors (age, work experience, and support by supervisors and coworkers) identified in previous research correlated with STS. However, a small positive association was found between STS and SPG. In the discussion section we warn against the use of interventions that aim to prevent STS until more is known about risk and protective factors for STS and provide directions for future research.

Molecular phenotype is associated with survival in breast cancer patients with spinal bone metastases.

To aid in therapy selection for patients with spinal bone metastases (SBM), predictive models have been developed. These models consider SBM from breast cancer a positive predictive factor, but do not take phenotypes based on estrogen (ER), progesterone (PR) and human epidermal growth factor 2 (HER2) receptors into account. The aim of this study was to ascertain whether receptors are associated with survival, when the disease has progressed up to SBM. All patients who were treated for SBM from breast cancer between 2005 and 2012 were included in this international multi-center retrospective study (n = 111). Reports were reviewed for ER, PR and HER2 status and subsequently subdivided into one of four categories; luminal A, luminal B, HER2 and triple negative. Survival time was calculated as the difference between start of treatment for SBM and date of death. Analysis was performed using the Kaplan-Meier method and log-rank tests. Median follow-up was 3.7 years. Survival times in the luminal B and HER2 categories were not significantly different to the luminal A category and were joined into a single receptor positive category. Eighty-five patients (77 %) had a receptor positive phenotype and 25 (23 %) had a triple negative phenotype. Median survival time was 22.5 months (95 %CI 18.0-26.9) for the receptor positive category and 6.7 months (95 %CI 2.4-10.9) for the triple negative category (p < 0.001). Patients with SBM from breast cancer with a triple negative phenotype have a shorter survival time than patients with a receptor positive phenotype. Models estimating survival should be adjusted accordingly.

Risk factors for survival of 106 surgically treated patients with symptomatic spinal epidural metastases.

PURPOSE: Evaluation of risk factors for survival in patients surgically treated for symptomatic spinal epidural metastases (SEM). METHODS: One hundred and six patients who were surgically treated for symptomatic SEM in a 10-year period in two cooperatively working hospitals were retrospectively studied for nine risk factors: age, gender, site of the primary tumor, location of the symptomatic spinal metastasis, functional and neurologic status, the presence of visceral metastases and the presence of other spinal and extraspinal bone metastases. Analysis was performed using the Kaplan-Meier method, univariate log-rank tests and Cox-regression models. RESULTS: Overall median survival was 10.7 months (0.2-107.5 months). Overall 30-day complication rate was 33 %. Multivariate Cox-regression analysis showed that fast growing primary tumors (HR 3.1, 95 % CI 1.6-6.2, p = 0.001), the presence of visceral metastases (HR 1.7, 95 % CI 1.0-2.9, p = 0.033) and a low performance status (HR 2.7, 95 % CI 1.1-6.6, p = 0.025) negatively influenced the survival. CONCLUSION: Primary tumor type, presence of visceral metastases and performance status are significant predictors for survival after surgery for symptomatic SEM and should be evaluated before deciding on the extent of treatment. More accurate prediction models are needed to select the best treatment option for the individual patient.

Access to HIV testing for sex workers in Bangkok, Thailand: a high prevalence of HIV among street-based sex workers.

We offered voluntary counseling and testing (VCT) for HIV and syphilis to women attending three public sexually transmitted infection (STI) clinics in Bangkok, Thailand from May 2004 to June 2006. The testing was performed at either one of three STI clinics in Bangkok or at mobile VCT in the same area as the outreach activity. Six-hundred eighty-four women were tested. The HIV prevalences among the street-based sex workers, brothel-based sex workers and other women in these areas not reporting sex work who tested in the clinics were 45.8% (38/83), 4.2% (10/236) and 9.9% (28/284), respectively. The prevalences of syphilis in these groups were 13.3%, 2.1%, and 2.6%, respectively. Street-based sex work and longer duration of sex work were independent risk factors for HIV in-fection (p < 0.001 and p = 0.02, respectively). HIV and syphilis prevalences were 21.0% and 3.7% among 81 street-based sex workers accepting mobile VCT, The street-based sex workers in Bangkok had substantially higher HIV and syphilis prevalences than other sex workers. Street-based sex workers should be sampled during routine surveillance to obtain systematic information on disease preva-lence and risk behaviors in this group.

Indicators for sexual HIV transmission risk among people in Thailand attending HIV care: the importance of positive prevention.

BACKGROUND: Almost half of all new HIV infections in Thailand occur among low-risk partners of people infected with HIV, so it is important to include people infected with HIV in prevention efforts. METHODS: Risk for HIV transmission was assessed among people with HIV attending routine care at the National Infectious Disease Institute in Thailand. Sexual risk behaviour, sexually transmitted infection (STI-syphilis, gonorrhoea, chlamydia, trichomoniasis and genital ulcers) prevalence and HIV disclosure status were assessed. Patients were provided with STI care, risk-reduction and HIV disclosure counselling. RESULTS: Baseline data were assessed among 894 consecutive people with HIV (395 men and 499 women) from July 2005 to September 2006. Unprotected last sex with a partner of unknown or negative HIV status (unsafe sex) was common (33.2%) and more likely with casual, commercial or male-to-male sex partners than with steady heterosexual partners (p = 0.03). People receiving antiretroviral treatment were less likely to report unsafe sex (p<0.001). Overall, 10.7% of men and 7.2% of women had a STI (p = 0.08). More women than men had disclosed HIV status to their steady partners (82.5% vs 65.9%; p = 0.05). CONCLUSION: Indicators for HIV transmission risk were common among people attending HIV care in Bangkok. Efforts need to be strengthened to reduce unsafe casual and commercial sex and to increase HIV disclosure from men to their partners. A strategy for STI screening and treatment for people with HIV in Thailand should be developed.

New trends in biological evaluation of medical devices.

More extensive material characterisation and increased determination of toxicological risks are now required when evaluating new medical devices. The new requirements together with other changes in the ISO 10993 series described here suggest how companies can adjust their approach.

Preclinical evaluation of medical devices.

Biological evaluation should be performed as part of risk assessment of the device. It can help define the toxicity and compatibility of the device. This article outlines which tests should be performed, with some examples of specific device test regimes.

Freund's complete adjuvant has a negative impact on egg laying frequency in immunised chickens.

The immunisation of chickens with Freund's Complete Adjuvant (FCA) significantly reduces the egg-laying frequency in comparison to the use of Freund's Incomplete Adjuvant and Hunter's TiterMax. Although FCA results in higher titers of immunospecific antibody in the egg yolk this is counter-balanced by the reduction in number of eggs produced by the chicken. There is consequently no reason to use FCA in chickens when the egg yolk is used as the antibody source.

Prediction of recurrent and residual cervical dysplasia by human papillomavirus detection among patients with abnormal cytology.

To determine the discriminative capacity of human papillomavirus (HPV) DNA testing for recurrent and residual cervical dysplasia, 43 patients with abnormal cytology after treatment for cervical dysplasia were tested for the presence of HPV DNA by PCR. An endocervical curettage was performed in all patients for histological examination. Sixteen of the 43 patients showed moderate or severe dysplasia. The HPV test was positive in all 16 patients with recurrent or residual dysplasia and negative in 12 of the 27 patients without dysplasia. The sensitivity and specificity of the HPV test were 100 and 44%, respectively. The likelihood ratio of a positive HPV test was 1.8, whereas a negative HPV test had a likelihood ratio of 0.12. Testing for the presence of HPV has the potential to select patients without recurrent or residual cervical dysplasia who have an abnormal cytological smear. This may have clinical implications, since unnecessary diagnostic conizations may be avoided in patients with abnormal cytology after treatment for cervical dysplasia and a negative HPV test.

Comparison of immunospecific antibody response in young and old chickens immunized with human IgG.

Three groups of 18-month-old chickens and three groups of 5-month-old chickens were immunized with human immunoglobulin G (IgG) using one of three adjuvants in the first injection (Freund's Complete Adjuvant (FCA), Freunds Incomplete Adjuvant (FIA) and Hunter's TiterMax (HTM)) following the same immunization scheme. The specific antibody response in serum was measured by ELISA. In both older and younger chickens the serum antibody response in the FCA group reached a significantly higher level (P < 0.01) than in the FIA group and in the HTM group on week 5. The FCA group also had a significantly higher (P < 0.01) response on week 10 compared to the HTM group. Other than that, there was no significant difference between the three adjuvant groups in specific serum antibody response in older chickens. In the younger chickens the specific serum antibody response in the FCA group was significantly higher (P < 0.05) than the response in the HTM group. There was no significant difference in the chicken serum antibody response between the FCA and the FIA groups, nor was there a significant difference between the FIA and the HTM groups. Comparing the younger chickens and the older chickens immunized using the same adjuvant, the older chickens had consistently higher titres than the younger chickens, although the difference was not always significant.

Development and comparison of assays for measuring immunospecific antibody response in serum of chickens and rabbits immunized with human immunoglobulin G.

The antibody response development during polyclonal antibody production is a relevant parameter to monitor during the immunization period to be able to optimize the immunization protocol and to determine the optimal antibody harvest time. Although rabbits and other mammals are most often used for polyclonal antibody production, the chicken is a relevant alternative. There are both scientific reasons, economic reasons, and animal welfare reasons to consider when choosing the chicken instead of a mammal for this purpose, because antibodies in generous quantities can be harvested from the egg yolk. This study compared different assays for measuring antibody response in rabbit and chicken serum. An inhibition liquid phase absorption assay (ILPAA), a rocket immunoelectrophoresis (RIE) assay, and a line immunoelectrophoresis (LIE) assay were compared to ELISAs. The ELISA proved to be the most useful assay for routine use, as it was less time-consuming and because the assay could easily be adapted to both serum antibody types. However, electrophoretic assays were the most useful as combined analytical and quantitative tools and must be considered essential when analyzing specificities of polyclonal antibody preparations.

Human papillomavirus deoxyribonucleic acid detection in mildly or moderately dysplastic smears: a possible method for selecting patients for colposcopy.

OBJECTIVE: Current screening protocols for cervical cancer dictate that patients with smears read as mild or moderate dysplasia of the uterine cervix undergo colposcopy, although approximately half these women do not prove to have high-grade squamous intraepithelial lesions. The aim of this study was to determine whether human papillomavirus testing is capable of discriminating between high- and low-grade squamous intraepithelial lesions so as to be useful in reducing the number of colposcopic examinations. STUDY DESIGN: We tested 190 consecutive patients with smears read as mild or moderate dysplasia for the presence of human papillomavirus deoxyribonucleic acid by use of two different polymerase chain reactions with the consensus primer pairs CPI/IIG and MY09/11. Typing was carried out by direct sequence analysis of the CPI/IIG amplimers. The MY09/11 amplimers were detected in enzyme-linked immunosorbent assay format with the SHARP (Solution Hybridization Assay for PCR Products) Signal System with two probe mixtures (A and B) to detect nononcogenic and oncogenic human papillomavirus types. The human papillomavirus test results were compared with the histologic diagnosis, which was regarded as the reference standard. RESULTS: Fifty-six of the 190 patients had high-grade squamous intraepithelial lesions. The sensitivity was 96% for the CPI/IIG test and 95% for the MY09/11 polymerase chain reaction plus SHARP Signal System when probe B only was used. The specificity was 33% for the CPI/IIG test and 40% for the MY09/11 polymerase chain reaction plus SHARP Signal System when probe B was used. CONCLUSION: A negative CPI/IIG or SHARP Signal System probe B test can select, respectively, 44 or 54 of the 134 patients without high-grade squamous intraepithelial lesions. The use of these human papillomavirus tests as a secondary triage in patients with smears that were read as mild or moderate dysplasia could prevent those patients from undergoing unnecessary colposcopy. However, respectively, 2 or 3 of the 56 patients who have high-grade squamous intraepithelial lesions would be missed by human papillomavirus testing.

Clearance of cervical human papillomavirus infection by treatment for cervical dysplasia.

OBJECTIVES: The aim of this study was to investigate the prevalence of human papillomavirus (HPV) after treatment for cervical dysplasia. STUDY DESIGN: The presence of HPV was investigated in cervical scrapes of 91 patients, before and after treatment, using consensus primers in the polymerase chain reaction. RESULTS: Before treatment for cervical dysplasia, 89 of 91 patients (98%) were HPV-positive compared with 28 of 91 patients (31%) after treatment. The HPV type present before treatment was found in the scrapes of only 9 of 89 patients (10%). Detection of HPV after treatment was associated with human immunodeficiency virus infection and incomplete conization. CONCLUSION: The HPV type present before treatment was frequently cleared by treatment for cervical dysplasia.

Immunoglobulin G in the developing oocytes of the domestic hen and immunospecific antibody response in serum and corresponding egg yolk.

The concentration of Immunoglobulin G (IgG) in developing oocytes from normal chickens was measured by ELISA. The concentration was similar in oocytes ranging in size from 6 mm to 38 mm, which is in the last stage of development before ovulation. The concentration of immunospecific IgG was similar in corresponding serum and yolk samples in chickens immunised with human IgG, and a significant linear correlation between response of a specific antibody in the serum and corresponding egg yolk was found. The serum antibody level had to reach a certain level before specific antibody appeared in the egg yolk, and the egg yolk to a certain extent reflected the serum concentration of IgG over 6 to 7 days; because this is the time it takes for the developing oocyte to grow from 6 to 35 mm in diameter.

Human papillomavirus DNA after treatment of cervical dysplasia: low prevalence in normal cytologic smears.

BACKGROUND: The presence of human papillomavirus (HPV) DNA in relation to cervical cytology was evaluated after treatment of cervical dysplasia. METHODS: Forty patients, 22 with normal and 18 with abnormal cytology (mild or moderate dyskaryosis), with a history of cervical dysplasia were selected. Only patients with HPV DNA positive biopsies obtained before treatment were included. The presence of HPV was assessed in cervical smears at least 1 year after treatment of cervical dysplasia by using a polymerase chain reaction (PCR) with consensus primers (CPI/IIG). HPV typing was done by direct sequence analysis of the CPI/IIG PCR generated amplimers. RESULTS: Smears from 3 of the 22 patients with normal cytology after treatment were positive for HPV DNA (14%). HPV DNA positive smears were found in 13 of the 18 patients with abnormal cytology after treatment (72%) (relative risk: 5.3; 95% confidence interval: 1.78-15.75). In 11 of the 16 HPV DNA positive smears (69%), the HPV type was different from that before treatment. In 35 of 40 patients, the HPV type before treatment could not be detected after treatment (88%). CONCLUSIONS: A minority of the patients with normal cytology after treatment of cervical dysplasia had detectable HPV DNA. In contrast, a high prevalence of HPV DNA was found in cervical smears of patients with abnormal cytology after treatment of cervical dysplasia. After treatment, none of the patients with abnormal cytology but HPV DNA negative smears had recurrence of cervical intraepithelial neoplasia. This suggests the value of supplementary HPV DNA testing during follow-up of patients treated for cervical dysplasia.

Antibody production in rabbits and chickens immunized with human IgG. A comparison of titre and avidity development in rabbit serum, chicken serum and egg yolk using three different adjuvants.

The antibody response in rabbits and chickens (serum and egg yolk) immunized with human immunoglobulin G was studied during a 1-year immunisation period comparing the efficacy of three adjuvants: Freund's complete adjuvant (FCA), Freund's incomplete adjuvant (FIA) and Hunter's TiterMax adjuvant (HTM). Monthly boosters of the antigen in saline were administered. Adjuvants were used in the initial immunisation and in a booster at week 26. FCA was found to result in the highest titre in both species. FIA was more efficient than HTM in mediating an antibody response in rabbits. In chickens, FIA resulted in similar antibody titres in serum and egg yolk. The effect of HTM was similar to FIA in chicken serum but lower in egg yolk. The titres obtained in rabbits were approximately a factor 1.5-2.0 higher than in the corresponding chicken groups. However, the antibody productivity of the chicken, when using the egg yolk as the antibody source, was a factor 5-10 higher than that of the rabbit depending on the adjuvant used. FCA and FIA resulted in similar antibody avidity in rabbits whereas HTM had a lesser effect. In chickens FCA initially resulted in the highest antibody avidity in both serum and egg yolk, but after the booster with adjuvant the antibody avidity became similar for all three adjuvants.

Intermethod variation in detection of human papillomavirus DNA in cervical smears.

In order to investigate the reliability of detection of human papillomavirus (HPV) DNA in cervical smears, we have compared the performance of two HPV PCR systems, the CPI/IIG and MY09/11 primer-mediated PCRs and the Hybrid Capture System HPV DNA detection test (hybrid capture assay), in detecting HPV DNA in cervical smears. We also included in our study the MY09/11B PCR plus SHARP (solution hybridization assay for PCR products) Signal System. This SHARP Signal System was recently developed to detect MY09/11B-generated biotinylated PCR products. The detection rate of the hybrid capture assay was lower than those of the CPI/IIG and MY09/11 PCRs and the MY09/11B PCR plus SHARP Signal System. The detection rates of the CPI/IIG PCR and the MY09/11B PCR plus SHARP Signal System were similar and higher than that of the conventional MY09/11 PCR system. The agreement beyond chance of the PCR methods was nearly perfect (kappa value between 0.82 and 0.84). The agreement beyond chance of the hybrid capture assay and the PCR methods was fair to good (kappa value between 0.64 and 0.70). The systems detected HPV DNA in different but overlapping sets of smears. Our results indicate that each of the detection methods alone underestimates the prevalence of HPV.