Health-related quality of life and disability in survivors of multiple trauma one year after intensive care unit discharge

OBJECTIVE: To evaluate health-related quality of life and disability in multiple-trauma patients requiring intensive care unit management. DESIGN: A total of 87 survivors of multiple trauma, with a median age of 31 yrs and a median Injury Severity Score of 22, were enrolled in the present study. The Nottingham Health Profile, Glasgow Outcome Scale, and Rosser Disability Scale were used to assess the functional consequences of trauma 1 yr after intensive care unit discharge. RESULTS: A total of 64 of 87 patients had a problem in at least one of the six domains related to subjective health status. The most prevalent complaint was related to somatic subdimensions, but emotional functioning was also affected. Nottingham Health Profile part 2 showed that 63 of the survivors experienced problems in at least one of the daily activities. Of particular importance, inability to work was reported by 47% of the patients. Fifty-nine percent experienced moderate-to-severe disability as evaluated by Glasgow Outcome Scale and Rosser Disability Scale. High aggregate injury severity score along with severe head trauma were independent predictors of poor health-related quality of life and disability. CONCLUSIONS: The majority of survivors of major trauma exhibit considerable levels of disability and impairment in health-related quality of life. Global injury severity score and degree of brain trauma determine functional limitations. This information may help in organizing long-term rehabilitation of multiple-trauma patients.     

Enzyme-linked immunosorbent assay of total inhibin: direct determination based on inhibin alpha subunit-specific monoclonal antibodies

OBJECTIVE: Inhibin circulates in various molecular weight forms. Alpha (alpha)-subunit-directed total inhibin immunoassays, which detect all forms of alpha subunits plus the alpha/beta inhibin dimers, have been found valuable in the diagnosis and monitoring of ovarian cancer. Because of the dependency of the published methods on boiling sample pre-treatment with SDS and unavailability of a commercial assay, we developed an enzyme-linked immunosorbent assay (ELISA) for direct determination of total inhibin. DESIGN AND METHODS: Method development involved a pair of well-characterized inhibin alpha subunit-directed antibodies and determination of the effects of various assay parameters. Selection of the optimized protocol was guided by the outcome of comparative sample analysis using previously reported boiling sample pre-treatment reagents and protocols. RESULTS: We report development of a simplified ELISA for total inhibin. Method evaluation data demonstrated acceptable analytical performance characteristics with detection limit of 2 ng/l (recombinant inhibin-A), dynamic range of 12.5-500 ng/l, and intra- and inter-assay imprecision of 2.3-4.6% and 3.3-5.1% at total inhibin concentrations of approximately 60-400 ng/l, respectively. The mean (+/-SD) recovery from spiked serum samples averaged 109 +/- 14% and recovery in response to serial sample dilution was 99 +/- 10%. Serum values by the direct method (n = 40) correlated strongly with those obtained after sample pre-treatment by boiling with SDS (r = 0.97). As expected, the total inhibin immunoreactivity in human follicular fluid fractionated by HPLC gel filtration in multiple immunoreactive peaks (8-250 kDa). In serum samples from postmenopausal women with ovarian cancer, the assay detected significantly higher total inhibin levels than in samples from normal postmenopausal controls. CONCLUSION: The development of a fast and simplified ELISA should facilitate wider investigations of pathophysiology and diagnostic potential of total inhibin measurement.     

Clarithromycin Leads to Long-Term Survival and Cost Benefit in Ventilator-Associated Pneumonia and Sepsis

Increasing numbers of admissions for sepsis impose a heavy burden on health care systems worldwide, while novel therapies have proven both expensive and ineffective. We explored the long-term mortality and hospitalization costs after adjunctive therapy with intravenous clarithromycin in ventilator-associated pneumonia (VAP). Two hundred patients with sepsis and VAP were enrolled in a published randomized clinical trial; 100 were allocated to blind treatment with a placebo and another 100 to clarithromycin at 1 g daily for three consecutive days. Long-term mortality was recorded. The hospitalization cost was calculated by direct quantitation of imaging tests, medical interventions, laboratory tests, nonantibiotic drugs and antibiotics, intravenous fluids, and parenteral and enteral nutrition. Quantities were priced by the respective prices defined by the Greek government in 2002. The primary endpoint was 90-day mortality; cumulative hospitalization cost was the secondary endpoint. All-cause mortality rates on day 90 were 60% in the placebo arm and 43% in the clarithromycin arm (P = 0.023); 141 patients were alive on day 28, and mortality rates between days 29 and 90 were 44.4% and 17.4%, respectively (P = 0.001). The mean cumulative costs on day 25 in the placebo group and in the clarithromycin group were €14,701.10 and €13,100.50 per patient staying alive, respectively (P = 0.048). Respective values on day 45 were €26,249.50 and €19,303.10 per patient staying alive (P = 0.011); this was associated with the savings from drugs other than antimicrobials. It is concluded that intravenous clarithromycin for three consecutive days as an adjunctive treatment in VAP and sepsis offers long-term survival benefit along with a considerable reduction in the hospitalization cost. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT00297674","term_id":"NCT00297674"}}NCT00297674.)     

Circulating levels of adhesion molecules and markers of endothelial activation in acute inflammation induced by prolonged brisk exercise

OBJECTIVES: To investigate circulating levels of adhesion molecules and markers of endothelial activation in acute inflammation induced by prolonged brisk exercise. DESIGN AND METHODS: The circulating levels of adhesion molecules E-, L- and P-selectins, intercellular and vascular adhesion molecule-1 (ICAM-1 and VCAM-1), along with those of thrombomodulin (TM), N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and cardiac troponin T, were measured before, at the end of and at 48 h post-race, in athletes participating in this extreme physical stress paradigm. RESULTS: Levels of L- and P-selectins remained the same before and at the end of the "Spartathlon" race, presenting a similar decline at 48 h post-race. E-Selectin, ICAM-1 and TM reached a maximum value at the end of the race and returned to normal 48 h after the race. A similar profile was observed for VCAM-1 and NT-pro-BNP, with a tendency for a decrease at 48 h post-race, while troponin T was not detected. CONCLUSIONS: The indices of endothelial activation are strongly affected during "Spartathlon" race, suggesting that, although prolonged brisk exercise activates the endothelium, it rapidly recovers.     

Nursing considerations for managing topotecan-related hematologic side effects

Topotecan (Hycamtin, SmithKline Beecham, Philadelphia, PA) was approved by the U.S. Food and Drug Administration in 1996 for use in relapsed ovarian cancer and in 1999 for platinum-sensitive small-cell lung cancer. Hematologic toxicity has been the predominant side effect associated with its use. Patients who have had extensive platinum-based therapy have exhibited increased degrees of thrombocytopenia and more severe neutropenia. These adverse events can be managed by identifying high-risk patients (i.e., those with more than six cycles of chemotherapy containing an alkylating agent or radiation to more than 25% of marrow-bearing bones, patients with a history of myelosuppression or renal impairment) and by recommending appropriate dose modifications based on the creatinine clearance measurement. By reducing the topotecan dose, myelosuppressive effects, as evidenced by neutropenia and thrombocytopenia, may be lessened or prevented without reducing the antitumor response.     

Long-term follow-up of International Prostate Symptom Score (IPSS) in men following prostate brachytherapy

Objective

To investigate variation in the International Prostate Symptom Score (IPSS) in men following prostate brachytherapy.

Methods

From January 2004 to November 2009, 524 consecutive patients underwent prostate brachytherapy either alone or in combination with external beam radiation therapy for T1c–T3b prostate cancer. The IPSS was assessed preimplant and at 1, 6, 12, 24, 36, and 48 months after treatment. Clinical and treatment-related factors were assessed for correlations with the IPSS increase.

Results

The mean preimplant IPSS was 7.4, with the greatest mean score of 16.0 at 1 month. At 6 months, the mean total IPSS had decreased to 11.5, but it was still statistically significantly greater than that at baseline (<0.001). At 12 months, the IPSS was decreased to 8.6, slightly greater than baseline (p = 0.001). The IPSS of 45.4 % (69/152) patients gradually returned to preimplant levels and that of 71.1 % (108/152) patients returned to within 3 points of the baseline at 24 months. At 24, 36, and 48 months after seed implantation, the IPSS was 8.6, 7.7, and 8.2, respectively, and none of these values differed statistically significantly from baseline (p > 0.05). Sixteen patients (3.1 %) showed AUR, and 11 patients required catheterization. On univariate and multivariate analyses, the IPSS increase was best predicted by lower preimplant IPSS.

Conclusion

In our series, IPSS after prostate brachytherapy peaked at 1 month and gradually returned to approximately baseline at 24 months. The IPSS increase was best predicted by lower preimplant IPSS.     

Direct Crosstalk Between Cancer and Osteoblast Lineage Cells Fuels Metastatic Growth in Bone via Auto‐Amplification of IL‐6 and RANKL Signaling Pathways

The bone microenvironment and its modification by cancer and host cell interactions is a key driver of skeletal metastatic growth. Interleukin‐6 (IL‐6) stimulates receptor activator of NF‐κB ligand (RANKL) expression in bone cells, and serum IL‐6 levels are associated with poor clinical outcomes in cancer patients. We investigated the effects of RANKL on cancer cells and the role of tumor‐derived IL‐6 within the bone microenvironment. Using human breast cancer cell lines to induce tumors in the bone of immune‐deficient mice, we first determined whether RANKL released by cells of the osteoblast lineage directly promotes IL‐6 expression by cancer cells in vitro and in vivo. We then disrupted of IL‐6 signaling in vivo either via knockdown of IL‐6 in tumor cells or through treatment with specific anti‐human or anti‐mouse IL‐6 receptor antibodies to investigate the tumor effect. Finally, we tested the effect of RANK knockdown in cancer cells on cancer growth. We demonstrate that osteoblast lineage‐derived RANKL upregulates secretion of IL‐6 by breast cancers in vivo and in vitro. IL‐6, in turn, induces expression of RANK by cancer cells, which sensitizes the tumor to RANKL and significantly enhances cancer IL‐6 release. Disruption in vivo of this auto‐amplifying crosstalk by knockdown of IL‐6 or RANK in cancer cells, or via treatment with anti‐IL‐6 receptor antibodies, significantly reduces tumor growth in bone but not in soft tissues. RANKL and IL‐6 mediate direct paracrine‐autocrine signaling between cells of the osteoblast lineage and cancer cells, significantly enhancing the growth of metastatic breast cancers within bone. © 2014 American Society for Bone and Mineral Research.