Protocol changes to reduce implant-associated infection rate after tibial plateau leveling osteotomy: 703 dogs, 811 TPLO (2006-2014).

OBJECTIVE: To determine the influence of a stricter aseptic protocol on implant-associated infection (IAI) rates after tibial plateau leveling osteotomy (TPLO). STUDY DESIGN: Retrospective cohort study. SAMPLE POPULATION: Seven hundred three dogs (811 TPLO). METHODS: Medical records (2006-2014) of dogs with TPLO with a ≥18-month follow-up were reviewed. An established TPLO protocol was altered to include an iodophore-impregnated adhesive drape, cefazolin administration every 90 minutes intraoperatively and then every 4 hours until hospital discharge, orthopedic surgical gloves, triclosan-coated intradermal sutures (instead of staples), soft-padded bandage with mupirocin ointment, use of single-use gloves while handling treated dogs, and placement of an Elizabethan collar. Signalment, affected limb, protocol changes, IAI, time to explant, and culture and susceptibility results were recorded. Data were analyzed by using Fisher's exact test, Wilcoxon rank-sum test, and a multivariable logistic regression model. RESULTS: TPLO plates were removed from 31 dogs (8.5% prechange, 1.3% postchange) because of a suspected IAI. Bacterial culture results from an explanted screw were positive in 26 dogs (7.4% prechange, 0.94% postchange). The odds ratio (OR) of IAI in the postchange cohort was decreased by 88% (OR 0.12, 95% CI 0.05-0.33) compared with the prechange cohort, after controlling for variables. Staphylococcus spp. were isolated from all implants removed from IAI-positive postchange dogs, 4/5 of which were methicillin resistant. No methicillin-resistant isolates were grown from the prechange cohort implants. CONCLUSION: The protocol tested here decreased IAI rates after TPLO, but most infections diagnosed after its implementation involved methicillin-resistant isolates. CLINICAL SIGNIFICANCE: The protocol reported here may be used as a guide in clinics seeking to reduce their IAI rates after TPLO. Postoperative infections after implementation of this protocol should be monitored to evaluate its potential impact on the emergence of antibiotic resistance.

Implant removal rate from infection after tibial plateau leveling osteotomy in dogs.

OBJECTIVE: To determine implant removal rate associated with infection after tibial plateau leveling osteotomy (TPLO) in dogs and to report antimicrobial susceptibility patterns for isolates. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs (n = 255; 282 TPLO). METHODS: Medical records (April 2006-April 2008) for dogs that had TPLO with ≥ 18 month follow-up were reviewed. Dogs that had implant removal with confirmed bacterial isolation from the implant were studied. Cefazolin (22 mg/kg intravenously) was administered before anesthesia induction for TPLO, every 2 hours intraoperatively, and every 6 or 8 hours until the next morning. Antimicrobial susceptibility testing was performed on isolates. RESULTS: Twenty-one (7.4%) of 282 TPLO required implant removal because of infection. Bacterial species isolated were Actinomyces spp. (1), Corynebacterium spp. (1), Enterococcus spp. (3), hemolytic Staphylococcus coagulase negative (2), nonhemolytic Staphylococcus coagulase negative (3), Staphylococcus spp. coagulase positive (7), methicillin-oxacillin-resistant Staphylococcus coagulase positive (2), and Serratia marcesens (2). Of the antibiotics that had ≥10 isolates tested against them, gentamicin had the highest susceptibility rate (94%), followed by tribrissen (71%), and amoxicillin/clavulanic acid (67%). CONCLUSION: Staphylococcus spp. was reported in 14 of the 21 infections cultured in this study. Based on antimicrobial susceptibility testing, amoxicillin/clavulanic acid would be the best empirical treatment.

Osteomyelitis-related sequestrum formation in association with the combination tibial plateau levelling osteotomy and cranial closing wedge osteotomy procedure.

A twenty-eight-month old female spayed American Bulldog was presented for evaluation of a chronic draining tract and intermittent left hindlimb lameness twenty-eight weeks after a combination tibial plateau levelling osteotomy and cranial closing wedge osteotomy (TLPO/CCWO) had been performed. The patient had developed an infection of the surgical site three weeks postoperatively. Drainage persisted despite implant removal 10 weeks postoperatively and several weeks of culture and sensitivity-directed antibiotic therapy. Twenty-eight weeks postoperatively, a sequestrum was identified on radiographs. Surgical removal of the sequestrum resulted in resolution of the drainage. While osteomyelitis is a known complication of TPLO surgery, this case represents the first described case of osteomyelitis-related sequestrum formation in association with the combined TPLO/CCWO procedure.

Formally defining medical processes.

OBJECTIVES: To demonstrate a technology-based approach to continuously improving the safety of medical processes. METHODS: The paper describes the Little-JIL process definition language, originally developed to support software engineering, and shows how it can be used to model medical processes. The paper describes a Little-JIL model of a chemotherapy process and demonstrates how this model, and some process analysis technologies that are also briefly described, can be used to identify process defects that pose safety risks. RESULTS: Rigorously modeling medical processes with Little-JIL and applying automated analysis techniques to those models helped identify process defects and vulnerabilities and led to improved processes that were reanalyzed to show that the original defects were no longer present. CONCLUSIONS: Creating detailed and precisely defined models of medical processes that are then used as the basis for rigorous analyses can lead to improvements in the safety of these processes.

Use of a (proposed) standard protocol to validate Terumo TSCD-II connections between dissimilar blood bag tubing.

BACKGROUND AND OBJECTIVES: ISO standards for blood bags do not adequately define and control the dimensions of blood bag transfer tubing. This lack of standardization presents potential difficulties when making sterile connections between the wide range of tubing that has evolved in the absence of such standards. We aim to validate the suitability of the TSCD-II and provide a minimum standard for assessing the suitability of sterile connections (welds) between dissimilar tubing. MATERIALS AND METHODS: The Terumo TSCD-II was used in this study to connect by hermetic welding seven tubing types with a wide range of dimensions from five suppliers. Thirty sterile connections were made between each combination split between dry/dry, wet/wet and dry/wet connections. Welds were assessed for visual defects, by tensile stress test (TST) and pressure tests. RESULTS: All welds passed visual inspection and pressure tests. All welds had a minimum tensile strength of greater than 40 N and mean of greater than 45 N. CONCLUSION: Successful connections have been made between dissimilar tube types and this work does not support the requirement for 'tight' tubing dimensional specifications. We have recommended to the ISO Technical Committee 76 Work Group 1 that ISO 3826-1 be revised and should include a minimum standard validation protocol for joining dissimilar tubing.

Neoadjuvant estramustine and etoposide followed by concurrent estramustine and definitive radiotherapy for locally advanced prostate cancer: feasibility and preliminary results.

PURPOSE: Current therapy for locally advanced prostate cancer is suboptimal. A treatment regimen was designed to improve systemic control by neoadjuvant targeting of hormone-sensitive and -insensitive micrometastatic disease and to improve local control by escalating the biologic effective dose to the prostate using estramustine (EMP) concurrently with radiotherapy. PATIENTS AND METHODS: Eighteen patients with locally advanced prostate cancer (Stages T3/T4 or T1c/T2b/T2c with a Gleason score of > or =7 and a serum PSA >15 ng/ml) were entered onto this trial. Therapy consisted of two 21-day cycles of oral estramustine (10 mg/kg/day) in three divided doses and oral etoposide (50 mg/m(2)/day, in two divided doses), followed by concurrent estramustine (10 mg/kg/day, PO) and three-dimensional conformal radiotherapy. RESULTS: Two patients required discontinuation of chemotherapy due to development of Grade 3 and 4 toxicity. All others completed both components of therapy per protocol guidelines. Minor toxicities included alopecia (100% of patients), anemia (69%), leukopenia (37%), thrombocytopenia (19%), and nausea (6%) but did not require dose modifications. There were no fatalities. Actuarial 3-year overall survival and disease-free survival (DFS) were 88% and 73%, respectively. Local control rate, assessed by repeated prostate biopsies at 18 months post completion of therapy, was 71%. CONCLUSION: The described regimen is well tolerated, and preliminary efficacy data are encouraging. The underlying concepts of early targeting of both hormone-sensitive and -insensitive micrometastatic clones, in combination with aggressive local therapy, warrant further investigation.

Metastatic melanoma from intraocular primary tumors: the Southwest Oncology Group experience in phase II advanced melanoma clinical trials.

Ocular melanoma is an uncommon malignancy that, in the presence of metastatic disease, has a poor prognosis for response to treatment and survival. Patients with ocular melanoma are often excluded from clinical trials because of the impression that these patients have a poorer response rate to treatment with anticancer agents and poorer survival, possibly related to the predominance of the liver as a site of metastasis. Sixty-four eligible patients with advanced melanoma arising from ocular primary tumors were entered into seven phase II clinical trials of anticancer therapy activated by the Southwest Oncology Group (SWOG) during the 1980s. Eligible patients with nonocular primaries entered into these trials (420 patients) served as a comparison group for survival, pretreatment characteristics, and response rates. Multivariate Cox model analysis of survival data (with survival from the time of study registration as the primary end-point) was conducted. Among the 484 patients observed, patients with ocular melanoma were older than those with nonocular primary tumors and were more likely to have visceral metastasis, metastasis to the liver, and only one metastatic site at registration, primarily to viscera and liver. The median overall survival after registration to study for both groups was 5 months. There was no significant difference in overall survival between patients with ocular melanoma and those with nonocular melanoma after adjusting for a number of prognostic factor (p = 0.43). Furthermore, the overall objective response rate of patients with ocular melanoma in these studies was not significantly different from that achieved in the nonocular group (9% vs. 11%; p = 1.00). Patients with advanced ocular or nonocular melanoma have similar response rates and survival in this series of cooperative group phase II trials. Patients with ocular primaries should not be excluded from investigational studies in advanced melanoma.

Systemic bone-seeking radionuclides for palliation of painful osseous metastases: current concepts.

Bone metastases require multidisciplinary treatment, the primary goal of which is to relieve pain and improve quality of life. Among the options available, bone-seeking radioisotopes are attractive because they can treat several symptomatic metastases simultaneously. This therapy may have antitumor efficacy in addition to analgesic properties. Although the ultimate place of systemic radionuclides in the treatment of bone metastases has not been firmly established, some patients clearly benefit from these modalities.

Binding of the Co(NH3)4 derivative of (2')3'-O-[N-methyl-anthraniloyl]-ATP to the E2ATP site of Na+/K+-transporting ATPase lowers the conformational flexibility of its E1ATP site.

Na+/K+-activated ATP hydrolysis by the sodium pump is catalyzed by the interaction of high-affinity and low-affinity ATP-binding sites [Thoenges, D. & Schoner, W. (1997) J. Biol. Chem. 272, 16315-16321]. To explore how binding of ATP to the low-affinity E2ATP site affects the conformational flexibility of the high-affinity E1ATP site due to interaction with Na+ or K+ ions, the E2ATP site was blocked with a fluorescent MgATP complex analog and fluorescence changes of the E1ATP site modified by FITC (fluorescein 5'-isothiocyanate) were studied. The fluorescent MgATP complex analog Co(NH3)4MANT-ATP [beta,gamma-bidentate complex of 2'(3')-O-(N-methylanthraniloyl)-ATP] inactivated Na+/K+-ATPase in a time-dependent and concentration-dependent process with a Kd of 0.17 mM and an inactivation rate constant, k, of 0.031 min(-1). ATP protected against the inactivation with a Kd of 0.43 mM. Consistent with a modification of the E2ATP binding site, Co(NH3)4MANT-ATP inactivated the K+-activated phosphatase activity in an enzyme whose E1ATP site had already been modified by FITC. Inactivation by Co(NH3)4MANT-ATP was due to tight binding which resulted in a loss of fluorescence. Tightly bound Co(NH3)4MANT-ATP could only be released by denaturation with SDS. Analysis of the conformational flexibility of the E1ATP site after labeling with FITC led to a K+-dependent quench of fluorescence which is reversed by Na+. This flexibility was lost upon the blockade of the E2ATP site by Co(NH3)4MANT-ATP.

Costsaving in the operating room: the Procedure Pack.

The concept of the Procedure Pack is very relevant in this era of managed care. By collecting more items in one pack, the hidden costs will be reduced and the pack will become relatively cheaper than the sum of every item. This paper compares the price of the Procedure Pack with the price of the separate items used for routine phaco-emulsification. The Procedure Pack is 2% more expensive, but the benefits by reducing the hidden costs are substantial and will be analyzed.

Osteosarcoma and other tumors of bone.

The report of results from a major randomized clinical trial of neoadjuvant chemotherapy for operable osteosarcoma and the experience of two groups with neoadjuvant chemotherapy for patients with malignant fibrous histiocytoma of bone mark the major clinical advances of the past year. Further work on prognostic factors, including p-glycoprotein, oncogenes, and genes related to cell cycle control, as well as promising novel therapeutics, appeared in the literature and will likely result in new areas of clinical investigation.

Osteosarcoma and other tumors of bone.

Steady progress in the delineation of prognostic factors and the identification of genetic alterations and of potential mechanisms of oncogenesis mark the contributions to the literature on osteosarcoma for the past year. A new cytokine and chemotherapy combination has shown promise, and additional work on chemotherapy regimens containing ifosfamide will undoubtedly stimulate interest in a new generation of randomized clinical trials that will be essential for further refinement of therapy for osteosarcoma.

Oral indomethacin and ranitidine in advanced melanoma: a phase II study.

As a result of preclinical data demonstrating the antitumour and antimetastatic efficiency of indomethacin in murine models, and the clinical observation of occasional tumour regression in patients with advanced melanoma treated with indomethacin together with ranitidine, a Phase II study was performed of prolonged administration of these two oral agents in combination. Seventeen patients were entered into the study and commenced on indomethacin 50 mg three times daily; the dose was escalated to a maximum of 75 mg three times daily in patients who tolerated the starting dose. Ranitidine was administered concurrently at a dose of 150 mg twice daily. One patient with uveal melanoma metastatic to the liver achieved a partial response, with slow shrinkage of a biopsy-proved liver metastasis (objective response rate 6 percent; 95 percent CI0-29). Another patient demonstrated a minor response in pelvic lymph nodes. The combination of indomethacin and ranitidine has negligible activity in advanced malignant melanoma; a response may require months to be achieved.

High-dose continuous venous infusion of interleukin-2: influence of dose and infusion rate on tumoricidal function and lymphocyte subsets.

Previous clinical studies have demonstrated a dose-response relationship between enhancement of certain immune parameters and interleukin-2 (IL-2) dose in trials with low dosages of the cytokine. This has not been demonstrated for high-dose (greater than 18 x 10(6) IU/m2 per day) IL-2. We completed phase II trials of sustained administration of indomethacin and ranitidine with IL-2 given as a continuous infusion over 5 days for three courses. Peripheral blood mononuclear cells, both fresh and cultured in vitro with IL-2 or IL-2 and indomethacin, were tested for tumoricidal function against K562 and Daudi targets; these results were then correlated with actual delivered dose and mean infusion rate per course. Similar correlations were calculated between delivered dose or infusion rate and absolute and proportional counts of lymphocyte subsets as determined by flow cytometry. No enhancement of in vitro tumoricidal function with either increasing delivered dose or increasing infusion rate was seen. No consistent pattern of correlation was found between the absolute counts of lymphocyte subsets after each course of IL-2 with delivered dose or infusion rate. The percent rise in absolute counts of selected T- and NK-cell subsets at the end of course 1 compared with baseline values correlated positively with infusion rate; however, a similar correlated between the infusion rate and an increase in lymphocyte tumoricidal function was lacking. Little evidence was found for improved tumoricidal function of mononuclear cells or consistent enhancement of lymphocyte subset counts in patients able to tolerate doses of IL-2 beyond 18 x 10(6) IU/m2 per day in a 5-day continuous infusion schedule.

Adjuvant chemotherapy for soft tissue sarcomas.

Despite considerable interest in this subject and the completion of a number of randomized trials, the use of adjuvant chemotherapy after definitive local treatment for patients with soft tissue sarcomas remains problematic. This article reviews randomized clinical trials completed and published to date, and explores new strategies for future studies.

Osteosarcoma and other tumors of bone.

Although no major advances in local or systemic therapy have been reported, further progress has been made in the identification of genetic alterations and prognostic factors in primary as well as recurrent osteosarcoma. Further reports on the use of a variety of imaging techniques in the quantification of tumor response to neoadjuvant chemotherapy have also appeared. Publications describing high-dose methotrexate pharmacokinetics, the impact of this therapy on patient outcome, and a report of a pilot study evaluating the feasibility of higher dose intensity cisplatin and doxorubicin may lead to new and important randomized clinical trials in the future.

[Why (some) psychoanalytic therapies (must) have a long duration. Thoughts on appropriate catamnestic methods]. / Warum (manche) Psychoanalysen lange dauern (müssen). Gedanken zum angemessenen katamnestischen Vorgehen.

First the author discusses some of the reasons why psychoanalytic therapy takes time, showing in the process how the psychoanalytic understanding of time is at odds with the everyday concept of it. He then makes out a case against the unthinking adoption of the psychometric procedures and evaluation techniques used hitherto in determining the success of psychotherapy. In this way certain erroneous developments in traditional psychology can be avoided in psychoanalytic catamnesis. In the concluding section the author outlines an alternative methodology of catamnesis geared to the specific epistemological requirements inherent in the process of psychoanalysis.

Localization and reactivity of an immunodominant domain in the NS3 region of hepatitis C virus.

Analysis of the amino acid sequences of the nonstructural region 3 (NS3) of the hepatitis C virus type 1 revealed four points with a high average hydrophilicity (Ah). Two of these potential antigenic sites were expressed in E. coli as short fragments. The first fragment of 91 residues (NS3f3: residues 1359-1449) harbors the hexapeptide K-K-K-C-D-E with an Ah of 2.33; the second fragment is 73 residues long (NS3f4: residues 1460-1532) and encompasses the heptapeptide R-S-N-R-R-G-R with an Ah of 1.79. Both fragments were expressed with truncated hepatitis B core (tHBc) as a carrier protein. The fusion proteins were purified from the bacterial lysates by affinity chromatography on immobilized monoclonal antibodies against HBc, and evaluated as antigens in an enzyme immunoassay for the detection of HCV antibodies. In a specificity control panel, reactivity with NS3f3 was only found in proven HCV carriers, while reactivity with NS3f4 was weak in HCV carriers but accounted for some of the nonspecific serological reactions. In a group of 48 genotyped HCV-infected volunteer blood donors, antibodies against NS3f3 were detected in 90% (27/30) of HCV-type 1 infections and in all HCV-type 4 infections (5/5).(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic significance of cellular proliferation in renal cell carcinoma: a comparison of synthesis-phase fraction and proliferating cell nuclear antigen index.

DNA aneuploidy has repeatedly been shown to be a significant prognostic indicator in renal cell carcinoma; however, few studies have emphasized the importance of measurements of cellular proliferation. This study evaluated 55 patients treated by radical nephrectomy and for whom clinical follow-up was available. There were 36 men and 19 women with a mean age of 61 yr. Robson stage distribution was I, 38 cases; II, five cases; and III, 12 cases. Flow cytometric analysis in 44 cases revealed 29 DNA diploid and 15 DNA aneuploid tumors with a median synthesis-phase fraction (SPF) of 4.4% (range 1.0 to 31.4%). The median proliferating cell nuclear antigen index was 3.9% (range 0.1 to 58.0%). There was a significant correlation between SPF and proliferating cell nuclear antigen index (R = 0.769) in the 33 cases in which both were available. Cellular proliferation, as determined by SPF, was a significant prognostic indicator (P < 0.02), but proliferating cell nuclear antigen index did not correlate with outcome (P > 0.05). Other significant predictors in this study were Robson stage (P = 0.03) and nuclear grade (P = 0.0003). DNA ploidy did not correlate with outcome (P > 0.05). We conclude that cellular proliferation, as measured by SPF analysis, is a significant predictor of outcome for renal cell carcinoma. Although the proliferating cell nuclear antigen index correlated with SPF, it did not achieve statistical significance as a prognostic indicator.