Citations

Abstract Background: Surgical site infections (SSI) contribute to surgical patients' morbidity and costs. Operating room traffic may be a modifiable risk factor for SSI. We investigated the impact of additional operating room personnel on the risk of superficial SSI (sSSI). Patients and Methods: In this matched case-control study, cases included patients in whom sSSI developed in clean surgical incisions after elective, daytime operations. Control subjects were matched by age, gender, and procedure. Operating room personnel were classified as (1) surgical scrubbed, (2) surgical non-scrubbed, or (3) anesthesia. We used conditional logistic regression to test the extent to which additional personnel overall and from each work group were associated with infection. Results: In total, 474 patients and 803 control subjects were identified. Each additional person among total personnel and personnel from each work group was significantly associated with greater odds of infection (all personnel, odds ratio [OR] = 1.082, 95% confidence interval [CI] 1.031–1.134, p = 0.0013; surgical scrubbed OR = 1.132, 95% CI 1.029–1.245, p = 0.0105; surgical non-scrubbed OR = 1.123, 95% CI 1.008–1.251, p = 0.0357; anesthesia OR = 1.153, 95% CI 1.031–1.290, p = 0.0127). After adjusting for operative duration, body mass index, diabetes mellitus, and vascular disease, additional personnel and sSSI were no longer associated overall or for any work groups (total personnel OR = 1.033, 95% CI 0.974–1.095, p = 0.2746; surgical scrubbed OR = 1.060, 95% CI 0.952-1.179, p = 0.2893; surgical non-scrubbed OR = 1.023 95% CI 0.907–1.154, p = 0.7129; anesthesia OR = 1.051, 95% CI 0.926–1.193, p = 0.4442). Conclusion: The presence of additional operating room personnel was not independently associated with increased odds of sSSI. Efforts dedicated to sSSI reduction should focus on other modifiable risk factors.

Abstract Objectives. Our purpose was to determine the incidence of surgical site infection (SSI) in cancer patients receiving an intrathecal drug delivery system (IDDS) and compare that rate with the incidence of SSI in the general population receiving an IDDS or spinal cord stimulator. We attempted to describe risk factors for SSIs in cancer patients treated with IDDS in terms of exposure to cancer treatments. Design. Retrospective review. Setting. Large tertiary care center. Patients. Cancer patients receiving an IDDS in 2006–2013. Methods. The incidence of SSI was determined according to the US Centers for Disease Control and Prevention definition. Medication regimens and current cancer treatment were investigated to identify immunocompromised patients during IDDS placement. Microbacteriology, treatment, and overall outcomes were investigated. Results. Sixty-four patients had an IDDS implanted in 2006–2013. SSI developed in four patients (6.2%). All four patients had received chemotherapy or radiotherapy within three months before implantation. Three of the three were receiving dexamethasone, and three of the four required explantation of the IDDS. Conclusion. The incidence of SSI was at the upper end of the published infection rates for IDDS. The risk of SSI may be increased in this population because of factors that alter the patient’s immune status, including concomitant corticosteroid use, radiotherapy near the SSI, and presence of immunomodulators. The identification and mitigation of certain risk factors for this population may prevent infection in future patients.

Abstract BACKGROUND Electrophoretic separation of serum and urine proteins has played a central role in diagnosing and monitoring plasma cell disorders. Despite limitations in resolution and analytical sensitivity, plus the necessity for adjunct methods, protein gel electrophoresis and immunofixation electrophoresis (IFE) remain front-line tests. METHODS We developed a MALDI mass spectrometry–based assay that was simple to perform, automatable, analytically sensitive, and applicable to analyzing the wide variety of monoclonal proteins (M-proteins) encountered clinically. This assay, called MASS-FIX, used the unique molecular mass signatures of the different Ig isotypes in combination with nanobody immunoenrichment to generate information-rich mass spectra from which M-proteins could be identified, isotyped, and quantified. The performance of MASS-FIX was compared to current gel-based electrophoresis assays. RESULTS MASS-FIX detected all M-proteins that were detectable by urine or serum protein electrophoresis. In serial dilution studies, MASS-FIX was more analytically sensitive than IFE. For patient samples, MASS-FIX provided the same primary isotype information for 98% of serum M-proteins (n = 152) and 95% of urine M-proteins (n = 55). MASS-FIX accurately quantified M-protein to <1 g/dL, with reduced bias as compared to protein electrophoresis. Intraassay and interassay CVs were <20% across all samples having M-protein concentrations >0.045 g/dL, with the ability to detect M-proteins <0.01 g/dL. In addition, MASS-FIX could simultaneously measure κ:λ light chain ratios for IgG, IgA, and IgM. Retrospective serial monitoring of patients with myeloma posttreatment demonstrated that MASS-FIX provided equivalent quantitative information to either protein electrophoresis or the Hevylite™ assay. CONCLUSIONS MASS-FIX can advance how plasma cell disorders are screened, diagnosed, and monitored.

Abstract BACKGROUND Current recommendations for screening for monoclonal gammopathies include serum protein electrophoresis (PEL), imunofixation electrophoresis (IFE), and free light chain (FLC) ratios to identify or rule out an M-protein. The aim of this study was to examine the feasibility of an assay based on immunoenrichment and MALDI-TOF-MS (MASS-SCREEN) to qualitatively screen for M-proteins. METHODS Serum from 556 patients previously screened for M-proteins by PEL and IFE were immunopurified using a κ/λ-specific nanobody bead mixture. Following purification, light chains (LC) were released from their heavy chains by reduction. MALDI-TOF analysis was performed and the mass-to-charge LC distributions were visually examined for the presence of an M-protein by both unblinded and blinded analysts. RESULTS In unblinded analysis, MASS-SCREEN detected 100% of the PEL-positive samples with an analytical sensitivity and specificity of 96% and 81% using IFE positivity as the standard. In a blinded analysis using 6 different laboratory personnel, consensus was reached in 92% of the samples. Overall analytical sensitivity and specificity were reduced to 92% and 80%, respectively. FLC ratios were found to be abnormal in 28% of MASS-SCREEN–negative samples, suggesting FLC measurements need to be considered in screening. CONCLUSIONS MASS-SCREEN could replace PEL in a panel that would include FLC measurements. Further studies and method development should be performed to validate the clinical sensitivity and specificity and to determine if this panel will suffice as a general screen for monoclonal proteins.

Abstract Therapeutic monoclonal immunoglobulins (mAbs) are used to treat patients with a wide range of disorders including autoimmune diseases. As pharmaceutical companies bring more fully humanized therapeutic mAb drugs to the healthcare market analytical platforms that perform therapeutic drug monitoring (TDM) without relying on mAb specific reagents will be needed. In this study we demonstrate that liquid-chromatography?mass spectrometry (LC?MS) can be used to perform TDM of mAbs in the same manner as smaller nonbiologic drugs. The assay uses commercially available reagents combined with heavy and light chain disulfide bond reduction followed by light chain analysis by microflow-LC?electrospray ionization-quadrupole-time-of-flight mass spectrometry (ESI-Q-TOF MS). Quantification is performed using the peak areas from multiply charged mAb light chain ions using an in-house developed software package developed for TDM of mAbs. The data presented here demonstrate the ability of an LC?MS assay to quantify a therapeutic mAb in a large cohort of patients in a clinical trial. The ability to quantify any mAb in serum via the reduced light chain without the need for reagents specific for each mAb demonstrates the unique capabilities of LC?MS. This fact, coupled with the ability to phenotype a patient?s polyclonal repertoire in the same analysis further shows the potential of this approach to mAb analysis.

Background: The use of progressive tension sutures has been shown to be comparable to the use of abdominal drains in abdominoplasty. However, the use of barbed progressive tension sutures (B-PTSs) in deep inferior epigastric artery perforator (DIEP) flap donor-site closure has not been investigated. Methods: A retrospective chart review was performed on patients with DIEP flap reconstruction in a 3-year period at 2 institutions by 2 surgeons. Patients were compared by method of DIEP donor-site closure. Group 1 had barbed running progressive tension sutures without drain placement. Group 2 had interrupted progressive tension closure with abdominal drain placement (PTS-AD). Group 3 had closure with only abdominal drain placement (AD). Data collected included demographics, perioperative data, and postoperative outcomes. Results: Seventy-five patients underwent DIEP reconstruction (25 B-PTS, 25 PTS-AD, and 25 AD). Patient characteristics—age, body mass index, comorbidities, smoking status, and chemotherapy—were not significantly different between groups. Rate of seroma was 1.3% (B-PTS = 0%, PTS-AD = 4%, AD = 0%), wound dehiscence 16% (B-PTS = 8%, PTS-AD = 16%, AD = 24%), and umbilical necrosis 5.3% (B-PTS = 0%, PTS-AD = 0%, AD = 16%). No hematomas were observed in any patients. No statistically significant difference was found between complication rates across groups. Conclusions: Use of B-PTSs for abdominal closure after DIEP flap harvest can obviate the need for abdominal drains. Complication rates following this technique are not significantly different from closure using progressive tension suture and abdominal drain placement. This practice can prevent the use of abdominal drains, which can promote patient mobility, increase independence upon discharge, and contribute to patient satisfaction.

Peloruside A, a microtubule-stabilizing agent isolated from a marine sponge, is a potential therapeutic candidate for the treatment of cancer, neurodegeneration, and autoimmune disease.