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At least 19 recordsLinked to original sources

Dissemination risk index based on plasminogen activator system components in primary breast cancer.

PURPOSE: To study interactions between disease-free survival (DFS) and four components of the plasminogen activator system: urokinase-type plasminogen activator (uPA), its two inhibitors (PAI-1 and PAI-2), and its membrane receptor uPAR. PATIENTS AND METHODS: We conducted a retrospective study of 499 primary breast cancer patients (median follow-up, 6 years). uPA, PAI-1, and PAI-2 were determined on cytosols and uPAR on solubilized pellets, using enzyme-linked immunoadsorbent assay kits (American Diagnostica, Greenwich, CT). Classical univariate and multivariate statistical methods were used together with multiple correspondence analysis to graphically examine interactions between the variables and outcome. RESULTS: By univariate analysis, higher uPA and PAI-1 values were significantly related to shorter DFS (P =.002; P <.00002). PAI-2 was not significantly related to DFS, although patients with high and very low PAI-2 values had a longer DFS. Multiple correspondence analysis showed the parallel impact of uPA and PAI-1 on outcome, and the clearly different behavior of PAI-2 compared with PAI-1. The prognostic contribution of uPAR seemed weak by both methods. A dissemination risk index [uPA x PAI-1/(PAI-2 + 1)], taking into account the modulation of uPA proteolytic activity by the ratio of its two inhibitors, was then tested. Dissemination risk index was selected as an independent variable in the Cox model in the overall population (P <.000001) and in node-positive patients (P <.00001). It was the only variable selected in node-negative patients (P =. 003). CONCLUSION: A dissemination risk index determined on primary tumor and taking into account the different effects of PAI-1 and PAI-2 on uPA can be of major help in clinical management of breast cancer, particularly in node-negative patients.

Adult↗

Saline infusion sonohysterography in endometrial cancer: assessment of malignant cells dissemination risk.

BACKGROUND: To assess the risk of malignant cells dissemination in patients with endometrial cancer undergoing saline infusion sonohysterography (SIS). METHODS: Fourteen consecutive patients (mean age: 58.1 years, range: 41-74 years) diagnosed as having a clinical stage I endometrial carcinoma and scheduled for surgical staging were entered in this study. SIS was performed at the time of laparotomy just when the abdomen was opened and prior to the start of the surgical procedure. 10-20 mL of saline was infused. All fluid spilled from the fimbrial ends of the fallopian tubes was collected and analyzed for the presence or absence of malignant endometrial cells. Samplings were also taken from ascites, if found, or cytological washings, prior to and after SIS. RESULTS: SIS could be satisfactorily performed in all patients. There was no spillage from either tube in nine patients. Mean fluid volume obtained from the other five patients was 4.4 mL. Cytologic analysis revealed the presence of malignant cells in the spilled fluid in one case (7.1%, one out of fourteen). CONCLUSIONS: Our data show that a small but real risk of malignant cell dissemination exists in patients with endometrial carcinoma who undergo SIS.

Adult↗

Shifts of antibiotic resistance genes across an estuarine meandering bend and dissemination risks to offshore oceans.

Meandering is a fundamental geomorphic feature of rivers that plays a critical role in regulating pollutant attenuation. To elucidate its impact on antibiotic resistance genes (ARGs) distribution in estuarine intertidal sediments, samples were collected from both the landward side (freshwater-dominated) and the seaward side (tide-dominated) of a meander bend during ebb and flood tides. The total relative abundance of ARGs was approximately 2.7 times higher on the landward side, peaking during the ebb tide. Microbial composition analysis showed that genera Acinetobacter and Pseudomonas were dominant at the landward sites, while halophilic genera such as Marinobacter and Exiguobacterium were abundant at the seaward sites. Further analysis of metagenome-assembled genomes (MAGs) demonstrated that the dominant landward genus Acinetobacter acted as a key host of ARGs, with two of four MAGs encoding more than ten ARGs. Notably, the total relative abundance of mobile genetic elements was high but consistent between sides and tidal cycles (p&#xa0;>&#xa0;0.05). Given this high dissemination risk, we further forecasted the ARGs transfer scenarios to oceanic settings based on a set of offshore MAGs (n&#xa0;=&#xa0;3626). Three ARGs, i.e., acrA, vanSL, and AAC(2')-Ia, were inferred to have transfer potential, supported by neighboring MGEs detected in marine microorganisms. Analysis of the genomes of predicted recipients in the SRA database confirmed the predicted mobilizations. Together, this study highlights that the meandering planform may serve as a significant barrier, attenuating the discharge of ARGs from terrestrial sources into the marine environment.

Estuaries↗

Feasibility and response to induction chemotherapy intensified with high-dose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma.

PURPOSE: To evaluate the feasibility of and response rate to an intensified induction chemotherapy regimen for young children with newly diagnosed high-risk or disseminated medulloblastomas. PATIENTS AND METHODS: From January 1997 to March 2003, 21 patients with high-risk or disseminated medulloblastoma were enrolled. After maximal surgical resection, patients were treated with five cycles of vincristine (0.05 mg/kg/wk x three doses per cycle for three cycles), cisplatin (3.5 mg/kg per cycle), etoposide (4 mg/kg/d x 2 days per cycle), cyclophosphamide (65 mg/kg/d x 2 days per cycle) with mesna, and methotrexate (400 mg/kg per cycle) with leucovorin rescue. Following induction chemotherapy, eligible patients underwent a single myeloablative chemotherapy cycle with autologous stem-cell rescue. RESULTS: Significant toxicities of this intensified regimen, including gastrointestinal and infectious toxicities, are described. Among the 21 patients enrolled, there were 17 complete responses (81%), two partial responses, one stable disease, and one progressive disease. The 3-year event-free survival and overall survival are 49% (95% CI, 27% to 72%) and 60% (95% CI, 36% to 84%), respectively. CONCLUSION: This intensified induction chemotherapy regimen is feasible and tolerable. With the majority of patients with disseminated medulloblastoma having M2 or M3 disease at diagnosis, the encouraging high response rate of this intensified induction regimen suggests that such an addition of methotrexate should be explored in future studies.

Antineoplastic Combined Chemotherapy Protocols↗

Successful treatment of good-risk disseminated testicular cancer with cisplatin, bleomycin, and reduced-dose vinblastine.

Cisplatin, vinblastine and bleomycin (PVB) is very effective therapy in disseminated testicular cancer, but toxicity is severe. A further reduction of vinblastine might reduce the acute toxicity of PVB without compromising the response rate in good-risk patients. Starting in March 1982, 42 consecutive patients with minimal or intermediate advanced disease (lymph node metastases less than 10 cm, lung nodules less than 5 cm) began a 0.2-mg/kg vinblastine PVB regimen, provided that serum alpha-fetoprotein (AFP) levels were not greater than 1000 ng/ml and human chorionic gonadotropin (HCG) values were not greater than 50,000 mIU/ml. Only 9 patients (21.4%) had leukocyte counts less than 1000/mm3, 6 (14%) had infections, but none had documented sepsis. Gastrointestinal and neuromuscular toxicities were mild. Of the 42 patients, 41 (97.6%) entered complete remission (CR), 8 with surgery. After a median follow-up period of 26 months (range, 19-40 months), 35 patients (83.3%) are continuously disease-free. Of the 6 patients with AFP levels greater than 400 ng/ml and/or HCG values greater than 1000 mIU/ml, only 2 (33.3%) entered continuous CR, versus 33 (91.6%) of the 36 patients with normal or less elevated markers (P less than 0.01). PVB with a 0.2-mg/kg vinblastine dosage is very effective and well-tolerated therapy in selected good-risk patients with disseminated germinal testis cancer.

Adolescent↗

The effect of a 7-day delay in chemotherapy cycles on complete response and event-free survival in good-risk disseminated germ cell tumor patients.

The effect of duration of induction treatment on complete response (CR) and event-free survival (EFS) (time to death or relapse) was evaluated in 162 "good-risk" germ cell tumor (GCT) patients treated from November 1982 to July 1986 in a randomized prospective trial with VAB-6 (cyclophosphamide + vinblastine + bleomycin + dactinomycin + cisplatin; 81 patients) versus etoposide + cisplatin (EP; 81 patients). Patients received three cycles of VAB-6 every 28 days or four cycles of EP every 21 days. Treatment cycle with either regimen was routinely postponed for 7 days for leukocytes less than 3000/mm3 or platelets less than 100,000/mm3 and then administered regardless of blood count. The number of treatment days was calculated for each patient from initial treatment day to final induction date plus 28 days for VAB-6 and plus 21 days for EP. The proportion of CR and the EFS for good-risk GCT patients treated with cisplatin-based chemotherapy were not influenced by a less than or equal to 7-day delay resulting from chemotherapy-induced myelosuppression. Short, planned delays in chemotherapy for good-risk GCT patients (less than or equal to 7 days per cycle) appear to be acceptable since they may prevent serious toxicity in this curable patient population. Delays of longer than 7 days are strongly discouraged except in extraordinary life-threatening circumstances.

Adolescent↗

The risk of disseminated Bacille Calmette-Guerin (BCG) disease in HIV-infected children.

OBJECTIVES: Bacille Calmette-Guerin (BCG), a live attenuated Mycobacterium bovis vaccine, poses a risk to human immunodeficiency virus (HIV)-infected children; this risk has not been well quantified. We estimate the risk of disseminated BCG disease in HIV-infected children in a setting highly endemic for tuberculosis and HIV. DESIGN AND METHODS: We conducted a prospective hospital-based surveillance study in the Western Cape Province, South Africa. Clinical and laboratory-confirmed cases of disseminated BCG disease in children<1 year of age from January 2002 to December 2004 at a referral hospital were used as numerator data. Denominator data for calculations of disseminated BCG risk were obtained through estimating the total number of HIV-infected infants receiving BCG based on the known vaccination coverage in the study setting, combined with population data on the total number of children<1 year of age, the known HIV prevalence amongst women attending public antenatal care facilities and different scenarios (5-15%) for the rate of vertical HIV transmission. RESULTS: Nine cases of disseminated BCG disease were identified over the study period, seven of these were in HIV-infected infants. The estimated risk for HIV-infected infants to develop disseminated BCG disease, given a 95% BCG coverage and an HIV prevalence of 12.4-15.4% amongst women, were as follows for different scenarios of vertical HIV transmission: 329-417/100,000 vaccinees (assuming 5% vertical HIV transmission), 164-208/100,000 vaccinees (assuming 10% vertical HIV transmission) and 110-139/100,000 vaccinees (assuming 15% vertical HIV transmission). CONCLUSIONS: The risk of disseminated BCG disease is increased several hundred fold in HIV-infected infants compared to the documented risk in HIV-uninfected infants. Data on the protective effect of BCG in HIV-exposed and infected children is lacking. Population- and hospital-based surveillance is vitally important to more accurately estimate the safety and benefits of BCG in HIV-exposed and infected infants.

AIDS-Related Opportunistic Infections↗

Risk of dissemination with biopsy of colorectal liver metastases.

PURPOSE: Liver surgeons usually recommend against biopsy of colorectal liver metastases because of the risk of local dissemination. To date, only case reports describing this problem have been published. This study is an attempt to quantify the risk of biopsy-related dissemination. METHODS: A multicenter, retrospective review was undertaken of cases of colorectal liver metastases presenting for surgery that had undergone a preoperative biopsy. RESULTS: Two hundred thirty-one cases of colorectal liver metastases presenting for surgery were identified. Forty-three cases had undergone a preoperative biopsy (18.6 percent). Seven patients had evidence of dissemination related to the biopsy, giving a risk of dissemination of 16 percent (95 percent confidence interval, 7-30 percent). The risk of dissemination was not related to the type of biopsy. Within the follow-up period (median, 21 months), 3 of the 7 cases with evidence of dissemination and 11 of the 35 without dissemination were alive without disease. Twenty-five percent of the 36 cases without dissemination were resected, whereas 6 of the 7 cases with dissemination were resected. CONCLUSIONS: There is a significant risk of local dissemination with biopsy of colorectal liver metastases. In this series this was independent of the type of biopsy. There was no demonstrated effect on resectability or survival, but numbers were small, and the median follow-up was short.

Aged↗

Intracranial tumors with risk of dissemination in neuroaxis.

The experience of the Radiotherapy Service, Clínica Puerta de Hierro, Madrid (Spain), in the treatment of intracranial tumors with risk of neural axis dissemination is analyzed. In 15 years (1964-1979) 415 primary central nervous system tumors were studied and treated; 67 corresponded to tumors with risk of meningeal dissemination. Clinical dissemination in cerebrospinal fluid was proven in 14 patients. The actuarial survival of 10 years for patients with neural axis dissemination, without prophylactic treatment to the neuroaxis, is 14% with an average survival of 10.5 months. In approximately 20% of meduloblastomas, ependymal and pineal region tumors, meningeal metastases at some distance from the primary tumor can take place. Patients at risk wtih these types of neoplasia must be identified, and an adequate radical therapeutic focus devised, not only for the primary tumor, but also for the risk of dissemination.

Adolescent↗

Risk of dissemination of cancer to flap donor sites during immediate reconstructive surgery.

We reviewed a series of 617 immediate reconstructions with distant flaps of defects caused by extirpation of malignant tumors to determine the incidence of tumor implantation in the flap donor sites. In this large series, there was only one instance of tumor dissemination to a flap donor site. We conclude that, despite possible theoretical concerns about host immunosuppression caused by surgical stress, the risk of tumor dissemination to flap donor sites as a consequence of immediate reconstruction is negligible.

Humans↗

[Risk of disseminating apiary diseases by international movements of bees and their products].

The evaluation of the risks of spreading bee diseases is based on information obtained from a wide variety of sources: reports of the world distribution of pathogenic agents; trade flow in bees and bee products; and observations and experimental data on the diseases. At present, this information is severely lacking and only enables a brief outline of trends to be made. Current data are inadequate to prevent the spread of diseases from one country to another. To improve this situation, it is important that exporting countries establish epidemiological and health surveillance practices based on harmonised procedures and diagnostic tests. In addition, the products of apiculture should be given a permanent, specific nomenclature, drawn up by the World Trade Organisation.

Animals↗

Hexaconazole enantiomers drive the dissemination and risks of antibiotic resistance genes in the soil-earthworm system.

Chiral fungicides constitute a substantial proportion of commonly used pesticides; however, the spread of antibiotic resistance genes (ARGs) in agricultural settings under repeated exposure to different enantiomers is still unclear. Here, the prevalence and potential risks of ARGs were investigated in the soil-earthworm ecosystem when exposed to hexaconazole (HEX) enantiomers. Metagenomic analysis indicated that R-HEX and S-HEX facilitated the dissemination of ARGs in soil without earthworms, but this effect diminished with successive exposures. Notably, S-HEX exhibited a greater effect on ARG profiles compared to R-HEX. Furthermore, HEX enantiomers, particularly S-HEX, increased the mobility potential of ARGs and enhanced host pathogenicity, thereby contributing to elevated ecological risks. Specifically, exposure to the HEX enantiomer led to an enrichment of dominant pathogenic ARG hosts, such as Enterobacteriaceae. Importantly, earthworms alleviated the enantiomer-driven dissemination of ARGs and weakened their association with mobile genetic elements (MGEs). Overall, this study offers novel perspectives on the enantiomer-driven propagation of ARGs induced by the chiral pesticide hexaconazole in soil and highlights the role of earthworms in mitigating ARG contamination. These findings contribute significantly to the risk assessment and remediation strategies for chiral pesticides.

Animals↗

[Risk of disseminated intravascular coagulation in patients undergoing echo-guided transperineal prostatic needle biopsy with transrectal probe].

Disseminated intravascular coagulation (DIC) is a severe life-threatening acute bleeding disorder. Traumatized tissues, tumors, necrotic tissues, or bacterial endotoxines release similar material in the blood to the tissutal factors activating the coagulation cascade. This preliminary study was aimed at verifying the risk of DIC in patients undergoing US-guided transperineal prostatic biopsy with Chiba and Tru-Cut needles. To evaluate the activation degree of coagulation factors in the circulation, the authors measured the concentrations of urinary fibrin degradation products in 10 patients undergoing US-guided transperineal prostatic biopsy, both before and after biopsy, every second hour, for 24 hours. Every tube of urine sample contained soya bean trypsin inhibitor and bovine thrombin to prevent any further fibrin degradation during incubation period for the possible presence of blood in urine samples. The results showed that 7/10 patients had marked increase in urinary fibrin degradation product levels (up to 800 micrograms%), with a 3-phase trend: early peak after 2-6 hours, middle peak after 6-14 hours, and late peak after 18-24 hours, which proved the activation of the coagulation cascade.

Aged↗

Clinical, microbiological, and immunological characteristics in HIV-infected subjects at risk for disseminated Mycobacterium avium complex disease: an AACTG study.

The clinical, microbiologic, and immunologic parameters in HIV-infected subjects first presenting with disseminated Mycobacterium avium complex (DMAC) were determined. Four HIV-positive groups not yet on DMAC treatment were enrolled: 19 subjects with CD4 lymphocyte counts < or =50/microl thought to have DMAC on clinical grounds; 18 subjects newly found to have a positive blood culture for MAC; 25 asymptomatic controls (CD4 cell counts < or =50); and 25 asymptomatic controls (CD4 counts 100-250/microl). Outcome measures include comparisons between groups for clinical characteristics; results of cultures from blood, marrow, and gastrointestinal and respiratory tracts; immunological markers from staining of marrow and flow cytometry of circulating lymphocytes; and cytokine production of PBMCs. Only 21% of the 19 patients entered on suspicion of having DMAC grew MAC from blood or marrow. Neither clinical presentation nor laboratory tests differentiated those culture-positive from those culture-negative patients. However, prior PCP or multiple other opportunistic infections were more common in the DMAC group. MAC was isolated from 82% of marrow and 50% of blood specimens from the DMAC group. Respiratory or gastrointestinal colonization was present in 36% of DMAC subjects, but only 5% of non-DMAC subjects with CD4 counts <50 cells/microl. CD8+ cells were more frequent in bone marrow, and CD4 cells recognizing MAC antigen were more frequent in blood from DMAC subjects vs. controls. Results suggest an early stage of tissue dissemination preceding persistent bacteremia, and mucosal entry without persistence of colonization. MAC-specific T cell responses apparently develop and persist during DMAC, but are dysfunctional or too infrequent to prevent persistence.

Adult↗