Comparing the performance of full-field digital mammography and digital breast tomosynthesis in the post-treatment surveillance of patients with a history of breast cancer: A retrospective study.

INTRODUCTION: The purpose of our study was to compare the performance of 2D (FFDM) against 3D (FFDM plus DBT) examinations in the post-treatment surveillance of asymptomatic breast cancer survivors. METHODS: A list of women with a history of breast cancer who underwent screening mammography (2D or 3D) from 5/2017 to 5/2020 was retrieved. A total of 20,210 examinations were identified and performance metrics were compared. RESULTS: There were no statistically significant difference in cancer detection rate (CDR) (p = 0.38), recall rate (RR) (p = 0.087), or positive predictive value (PPV) (p = 0.74) between 2D vs. 3D examinations. Stratification by breast tissue identified no statistically significant difference in CDR (p = 0.581 and p = 0.428), RR (p = 0.230 and p = 0.205), or PPV (p = 0.908 and p = 0.721) between fatty/scattered and heterogeneous/extremely dense breast tissue when comparing 2D vs 3D examinations. Stratification by age did not identify a significant difference in RR or PPV between the two groups. CDR was statistically increased with 2D vs. 3D examinations in the 60-69 years group (p = 0.021). Stratification by race did not identify a significant difference in RR or PPV between the two groups. CDR was statistically increased with 3D vs. 2D examinations in white women (p = 0.036). Stratification by laterality (bilateral vs. unilateral post mastectomy) did not identify a significant difference in RR or PPV between the two groups. CDR was statistically increased in 2D vs. 3D examinations in unilateral studies (p = 0.009). CONCLUSION: For asymptomatic women with a history of breast cancer, there is no evidence that the addition of DBT to FFDM improves CDR, RR, or PPV. IMPLICATIONS FOR PRACTICE: More studies are needed concerning screening methodologies supplementing FFDM in the screening regimens of breast cancer survivors.

OncotypeDX Recurrence Score Does Not Predict Nodal Burden in Clinically Node Negative Breast Cancer Patients.

BACKGROUND: OncotypeDX recurrence score (RS)® has been found to predict recurrence and disease-free survival in patients with node negative breast cancer. Whether RS is useful in guiding locoregional therapy decisions is unclear. We sought to evaluate the relationship between RS and lymph node burden. METHODS: Patients with invasive breast cancer who underwent sentinel lymph node dissection from 2010 to 2015 were identified from a prospectively maintained database. Patients were excluded if they were clinically node positive or if they received neoadjuvant chemotherapy. RS was classified as low (< 18), intermediate (18-30), or high (> 30). The association between RS, lymph node burden, and disease recurrence was evaluated. Statistical analyses were performed in R version 3.4.0; p < 0.05 was considered significant. RESULTS: A positive SLN was found in 168 (15%) of 1121 patients. Completion axillary lymph node dissection was performed in 84 (50%) of SLN-positive patients. The remaining 84 (50%) patients had one to two positive SLNs and did not undergo further axillary surgery. RS was low in 58.5%, intermediate in 32.6%, and high in 8.9%. RS was not associated with a positive SLN, number of positive nodes, maximum node metastasis size, or extranodal extension. The median follow-up was 23 months. High RS was not associated with locoregional recurrence (p = 0.07) but was significantly associated with distant recurrence (p = 0.0015). CONCLUSIONS: OncotypeDX RS is not associated with nodal burden in women with clinically node-negative breast cancer, suggesting that RS is not useful to guide decisions regarding extent of axillary surgery for these patients.

Surveillance of women with a personal history of breast cancer by tumour subtype.

AIM: To determine if the rate and timing of a second breast cancer event (SBCE) in women with a personal history of breast cancer varies by disease subtype or breast imaging method. MATERIALS AND METHODS: A retrospective review was performed of women with a SBCE from January 2006 to December 2010 at a single institution. Data analysed included oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status of the primary and second breast cancers; mammographic and ultrasound (US) features from SBCE; and the time interval between both events. RESULTS: Of 207 patients diagnosed with a SBCE, the median age at first diagnosis was 50.6 years, range 24.8 to 80.2; at second diagnosis was 56.2 years, range 25.8 to 87.9. Eleven percent of SBCE were diagnosed >10 years after the primary cancer diagnosis. The median time between the first and second diagnosis for ER-positive patients was 2.7 years (range 0.7-17.4 years); and 1.9 years for ER-negative patients, (range 0.4-23.4 years; p<0.002). Patients with triple-negative breast cancer (TNBC) had a shorter time between diagnoses than others (p=0.0003). At 3, 5, and 10 years, 85%, 92%, and 97% of ER-negative and 54%, 81%, and 95% of ER-positive tumours, respectively, had recurred. ER-negative tumours and TNBC were more likely to be visible at US. CONCLUSION: There may be a role for customised imaging surveillance of women with a personal history of breast cancer (PHBC) after 10 years. Further studies are necessary to determine if US may be valuable in the surveillance of patients with ER-negative and TNBC tumours.

Bendamustine added to allogeneic conditioning improves long-term outcomes in patients with CLL.

Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=<0.001). The 3-year overall survival estimates for the BFR and FCR groups were 82 and 51% (P=0.03), and the 3-year PFS estimates were 63% and 27% (P=0.001), respectively. The 2-year treatment-related mortality was 8 and 23% and the incidence of grade 3 or 4 GvHD was 4% and 10%, respectively. This study is the first to report that addition of bendamustine to alloSCT conditioning for CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.

Is MRI helpful in assessing the distance of the tumour from the internal os in patients with cervical cancer below FIGO Stage IB2?

AIM: To determine the ability of magnetic resonance imaging (MRI) in detecting tumour-free margins from the internal os (IO). MATERIALS AND METHODS: A database search yielded 79 women with early-stage cervical cancer who underwent radical hysterectomy and preoperative MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MRI in assessment of ≤5 and >5 mm IO involvement were calculated with histopathological surgical specimen findings considered to be the reference standard. A main and subset analysis was performed. The subset analysis included only those patients who would have been considered for radical trachelectomy. RESULTS: For predicting a distance between the tumour and the IO of ≤5 mm, MRI had a sensitivity of 73%, a specificity of 98.3%, a PPV of 95%, a NPV of 88.1%, and an accuracy of 89.8% for the main analysis, and sensitivity of 81.8%, a specificity of 93.2% a PPV of 69.2% a NPV of 96.5% and an accuracy of 91.4% for the subset analysis. CONCLUSION: MRI has high specificity, NPV, and accuracy in detecting tumour from the IO, making MRI suitable for treatment planning in patients desiring trachelectomy to preserve fertility.

Allogeneic stem-cell transplantation in patients with cutaneous lymphoma: updated results from a single institution.

BACKGROUND: Cutaneous T-cell lymphomas (CTCLs) and its common variants mycosis fungoides (MF) and leukemic Sézary syndrome (SS) are rare extranodal non-Hodgkin's lymphomas. Patients who present with advanced disease and large-cell transformation (LCT) are incurable with standard treatments. In this article, we report the largest single-center experience with allogeneic stem-cell transplantation (SCT) for advanced CTCL. PATIENTS AND METHODS: This is a prospective case series of 47 CTCL patients who underwent allogeneic SCT after failure of standard therapy between July 2001 and September 2013. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) curves. The method of Fine and Gray was used to fit regression models to the same covariates for these cumulative incidence data. RESULTS: The Kaplan-Meier estimates of OS and PFS at 4 years were 51% and 26%, respectively. There was no statistical difference in the OS in patients who had MF alone, SS, MF with LCT, or SS with LCT. PFS at 4 years was superior in patients who had SS versus those who did not (52.4% versus 9.9%; P = 0.02). The cumulative incidences of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD were 40% and 28%, respectively. The cumulative nonrelapse mortality rate was 16.7% at 2 years. CONCLUSION: Allogeneic SCT may result in long-term remissions in a subset of patients with advanced CTCL. Although post-SCT relapse rates are high, many patients respond to immunomodulation and achieve durable remissions. CLINICALTRIALSGOV: NCT00506129.

Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor-risk relapsed or refractory germ-cell tumors.

BACKGROUND: High-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However, outcomes of high-risk patients in advanced relapse remain poor. We previously developed a new HDC regimen combining infusional gemcitabine with docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in refractory GCT. Given the high vascular endothelial growth factor expression in metastatic GCT and the synergy between bevacizumab and chemotherapy, we studied concurrent bevacizumab and sequential HDC using GemDMC and ifosfamide/carboplatin/etoposide (ICE) in patients with poor-risk relapsed or refractory disease. PATIENTS AND METHODS: Eligibility criteria included intermediate/high-risk relapse (Beyer Model), serum creatinine ≤ 1.8 mg/dl and adequate pulmonary/cardiac/hepatic function. Patients received sequential HDC cycles with bevacizumab preceding GemDMC (cycle 1) and ICE (cycle 2). The trial was powered to distinguish a target 50% 2-year relapse-free survival (RFS) from an expected 25% 2-year RFS in this population. RESULTS: We enrolled 43 male patients, median age 30 (20-49) years, with absolute refractory (N = 20), refractory (N = 17) or cisplatin-sensitive (N = 6) disease, after a median 3 (1-5) prior relapses. Disease status right before HDC was unresponsive (N = 24, progressive disease 22, stable disease 2), partial response with positive markers (PRm(+)) (N = 8), PRm(-) (N = 7) or complete response (N = 4). Main toxicities were mucositis and renal. Four patients (three with baseline marginal renal function) died from HDC-related complications. Tumor markers normalized in 85% patients. Resection of residual lesions (N = 13) showed necrosis (N = 4), mature teratoma (N = 2), necrosis/teratoma (N = 3) and viable tumor (N = 4). At median follow-up of 46 (9-84) months, the RFS and overall survival rates are 55.8% and 58.1%, respectively. CONCLUSIONS: Sequential bevacizumab/GemDMC-bevacizumab/ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the results expected in this difficult to treat population. CLINICALTRIALSGOV: NCT00936936.

A phase I study of decitabine with pegylated interferon α-2b in advanced melanoma: impact on DNA methylation and lymphocyte populations.

BACKGROUND: Melanoma cell lines treated with decitabine show upregulation of cancer antigens, and interferon-α upregulates MHC Class I antigens in cancer cells, leading to enhanced T-cell recognition and T-cell mediated tumor apoptosis. We evaluated the synergy between the hypomethylating effects of decitabine and the immunomodulatory effects of interferon in a combination regimen administered to advanced melanoma patients in a phase 1 trial. METHODS: Patients with one prior systemic therapy were eligible. Using a modified 3 + 3 design, patients received escalating doses of decitabine and pegylated interferon α-2b (PEG-IFN) during every 28-day treatment cycle. Global DNA methylation was measured on days 1 and 5 of cycles 1 and 3. Cytokine profiling and quantification of T-cell subpopulations by FACS were performed at baseline and cycle 3. RESULTS: Seventeen patients were assigned to one of four dose levels. Decitabine 15 mg/m2/d + PEG-IFN 3 µg/kg was the maximum tolerated dose (MTD). Grade 3/4 cytopenias were seen across all dose levels: anemia (1), neutropenia (7), and thrombocytopenia (2). One patient remained progression-free for 37 weeks. The other 16 patients progressed at or before 12 weeks. Median overall survival was 39 weeks. Hypomethylation was seen at all dose levels. Due to treatment-induced lymphocytopenia, absolute changes in T-cell populations post-treatment were too small to be meaningfully interpreted. CONCLUSIONS: The response to this combination regimen was characterized by significant myelosuppression, particularly neutropenia. Although disappointing efficacy and slow accrual led to early closure of the trial, hypomethylation showed pharmacodynamic evidence of a therapeutic effect of decitabine at all dose levels.

Consistency of response and image recognition, pulmonary nodules.

OBJECTIVE: To investigate the effect of recognition of a previously encountered radiograph on consistency of response in localized pulmonary nodules. METHODS: 13 radiologists interpreted 40 radiographs each to locate pulmonary nodules. A few days later, they again interpreted 40 radiographs. Half of the images in the second set were new. We asked the radiologists whether each image had been in the first set. We used Fisher's exact test and Kruskal-Wallis test to evaluate the correlation between recognition of an image and consistency in its interpretation. We evaluated the data using all possible recognition levels-definitely, probably or possibly included vs definitely, probably or possibly not included by collapsing the recognition levels into two and by eliminating the "possibly included" and "possibly not included" scores. RESULTS: With all but one of six methods of looking at the data, there was no significant correlation between consistency in interpretation and recognition of the image. When the possibly included and possibly not included scores were eliminated, there was a borderline statistical significance (p = 0.04) with slightly greater consistency in interpretation of recognized than that of non-recognized images. CONCLUSION: We found no convincing evidence that radiologists' recognition of images in an observer performance study affects their interpretation on a second encounter. ADVANCES IN KNOWLEDGE: Conscious recognition of chest radiographs did not result in a greater degree of consistency in the tested interpretation than that in the interpretation of images that were not recognized.

Thickness of superficial basal cell carcinoma (sBCC) predicts imiquimod efficacy: a proposal for a thickness-based definition of sBCC.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in the white population. It is an important driver of healthcare costs and causes significant morbidity. Topical imiquimod is a good noninvasive treatment alternative for surgical excision in superficial BCC (sBCC). However, there are currently no uniform histological definitions of sBCC. A definition based on tumour thickness might be a good alternative. OBJECTIVES: To determine whether tumour thickness in sBCC is a predictor of treatment failure. METHODS: We retrospectively examined 127 histological biopsy specimens of sBCC treated primarily with imiquimod five times a week for 6 weeks. Mean follow-up was 34 months (range 3-91). Recurrence was evaluated clinically with histological verification. RESULTS: Among nonrecurrent cases the median tumour thickness was 0·26 mm (range 0·09-0·61), while for recurrent cases the median tumour thickness was 0·57 mm (range 0·41-1·41, P < 0·0001). Among lesions ≤ 0·40 mm in thickness, none recurred, whereas for lesions > 0·40 mm the recurrence rate was 58% (P < 0·0001). CONCLUSIONS: We recommend the use of tumour thickness to define the superficial pattern in pathology reports for BCC as this can help to determine treatment response of sBCC to imiquimod.

Outcomes of second allogeneic hematopoietic stem cell transplantation for patients with acute lymphoblastic leukemia.

For patients with ALL who relapse following allo-SCT, only a second SCT provides a realistic chance for long-term disease remission. We retrospectively analyzed the outcomes of 31 patients with relapsed ALL after a prior allo-SCT, who received a second SCT (SCT2) at our center. With a median follow-up of 3 years, 1- and 3-year PFS was 23 and 11% and 1- and 3 year OS rates were 23 and 11%. Twelve patients (39%) were transplanted with active disease, of whom 75% attained a CR. We found a significant relationship between the time to treatment failure following first allograft (SCT1) and PFS following SCT2 (P=0.02, hazard ratio=0.93/month). In summary, a second transplant remains a potential treatment option for achieving response in a highly refractory patient population. While long-term survival is limited, a significant proportion of patients remains disease-free for up to 1 year following SCT2, providing a window of time to administer preventive interventions. Notably, our four long-term survivors received novel therapies with their second transplant underscoring the need for a fundamental change in the methods for SCT2 to improve outcome.

Metaplastic sarcomatoid carcinoma of the breast appears more aggressive than other triple receptor-negative breast cancers.

Metaplastic sarcomatoid carcinoma (MSC) of the breast is usually triple receptor (ER, PR, and HER2) negative and is not currently recognized as being more aggressive than other triple receptor-negative breast cancers. We reviewed archival tissue sections from surgical resection specimens of 47 patients with MSC of the breast and evaluated the association between various clinicopathologic features and patient survival. We also evaluated the clinical outcome of MSC patients compared to a control group of patients with triple receptor-negative invasive breast carcinoma matched for patient age, clinical stage, tumor grade, treatment with chemotherapy, and treatment with radiation therapy. Factors independently associated with decreased disease-free survival among patients with stage I-III MSC of the breast were patient age > 50 years (P = 0.029) and the presence of nodal macrometastases (P = 0.003). In early-stage (stage I-II) MSC, decreased disease-free survival was observed for patients with a sarcomatoid component comprising ≥ 95% of the tumor (P = 0.032), but tumor size was the only independent adverse prognostic factor in early-stage patients (P = 0.043). Compared to a control group of triple receptor-negative patients, patients with stage I-III MSC had decreased disease-free survival (two-sided log rank, P = 0.018). Five-year disease-free survival was 44 ± 8% versus 74 ± 7% for patients with MSC versus triple receptor-negative breast cancer, respectively. We conclude that MSC of the breast appears more aggressive than other triple receptor-negative breast cancers.

SU-E-J-37: Radiation Dose during Chemoembolization: A Predictive Model.

PURPOSE: To identify variables correlated with radiation dose during hepatic chemoembolization, quantify their individual impact, and apply these findings to build a dose prediction model. METHODS: A retrospective review of 77 patients undergoing hepatic chemoembolization between 1/2010-10/2010 was performed. Variables included: Radiation dose metrics[DAP, CD, number of cone beam CT and fluoroscopy time] and clinical parameters(BMI, session number, extrahepatic embolization, lesion number, chemoembolization regimen and lobe(s) treated). CD was the primary outcome measurement used for the dose model. Univariate and multivariate linear regression models were used to assess the association between dose metrics and predictive variables and assess the relative impact of each variable on dose. Variables were considered statistically significant at the p<0.05 level. Coefficient of determination(R2)and root mean square error(RMSE) were calculated for CD. R2 was used to evaluate goodness of fit and RMSE was used to establish a measurement of the typical size of the error in predicting the cumulative dose. RESULTS: Based on the multivariate analysis: higher BMI, regimen, single lesions, 1° tumor and initial session were statistically significant and incorporated into the following dose prediction model: Predicted Dose(mGy)= -672+BMI(56.3)+558(session #1)+1789(extrahepatic a. embolized)+232(1°tumor)+[-667(2-4 lesions)or - 12(>5 lesions)]+[370(dox-bead regimen)or 1618(ethiodol based regimen)]. Plots of the predicted vs actual CD were performed and the adjusted R2 for CD is 52.9%(RMSE = 697). The model is accurate at predicting 52% of the variation. When the model predicts a dosage of 1000 or 2000 mGy the actual dose interval ranges from 519-2519 mGy or 384-3616 mGy, respectively. CONCLUSIONS: Creating a radiation dose prediction model is feasible. This is the first known attempt at creating a dose model for image guided intervention and refinements to the model will be required to improve its accuracy. Prospective dose modeling will become more relevant as the cost benefit analysis of radiation exposure enters the decision making process in patient care. Alda Tam: Angiodynamics Inc., research funding Joseph Steele: MedicaSafe, Inc ownership Intelliject medical ownership INTIO medical consultant/ownership Caymus Medical ownership Cayenne Medical ownership.

Can we use medical examiners' records for suicide surveillance and prevention research in Nova Scotia?

INTRODUCTION: Medical examiners' records can contribute to our understanding of the extent of suicide in a population, as well as associated sociodemographic and other factors. METHODS: Using a mixed methods approach, the key objective of this pilot study was to determine the sources and types of information found in the Nova Scotia Medical Examiner Service (NSMES) records that might inform suicide surveillance and targeted prevention efforts. A secondary objective was to describe the one-year cohort of 108 individuals who died by suicide in 2006 in terms of available sociodemographic information and health care use in the year prior to death. RESULTS: Data extraction revealed inconsistencies both across and within files in terms of the types and amounts of sociodemographic and other data collected, preventing correlational analyses. However, linkage of the records to administrative databases revealed frequent health care use in the month prior to death. CONCLUSION: The introduction of systematic data collection to NSMES investigations may yield a comprehensive dataset useful for policy development and population level research.

Analytical identification of additional impurities in urinary-derived gonadotrophins.

Advances in proteomic technology have enabled contaminant proteins to be identified from complex protein mixtures. The purity of two purified urinary gonadotrophin products, human menopausal gonadotrophin (u-HMG) and human FSH (u-hFSH), was compared with a preparation of recombinant human FSH (r-hFSH). After separation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), western blot analysis showed that the recombinant preparation contained only FSH, whereas the urine-derived preparations exhibited several non-FSH or LH-related bands. These urinary components were further investigated by a proteomic approach using two-dimensional SDS-PAGE followed by mass spectrometric identification. The proteomic approach detected a total of 23 non-gonadotrophin-related proteins, at variable levels in different batches of the urine-derived preparations. Of these, 16 co-purified proteins have not been previously reported to be present in urine-derived gonadotrophins. These results indicate that the process used to purify urinary gonadotrophins may not remove all non-gonadotrophin proteins. By using a comprehensive proteomic approach, it has been shown that the recombinant FSH preparation has greater purity than either of the urine-derived preparations.

A pilot study examining correlates of body image among women living with SCI.

STUDY DESIGN: Cross-sectional pilot study. OBJECTIVES: To explore correlates of body image among women with spinal cord injury (SCI), within the framework of Cash's cognitive behavioral model of body image. SETTING: Hamilton, Ontario, Canada. METHODS: Women with SCI (N=11, 64% with tetraplegia) reported their functional and appearance body image (Adult Body Satisfaction Questionnaire). A 3-day recall of leisure time physical activity (LTPA), three measures of body composition (that is, weight, waist circumference, body fat) and several demographic variables were assessed as potential correlates. RESULTS: Appearance satisfaction was negatively correlated with all three measures of body composition and positively correlated with years postinjury. Functional satisfaction was positively correlated with years postinjury, and negatively correlated with various LTPA variables. CONCLUSION: Functional and appearance body image may improve with time following SCI. Body composition may impact satisfaction with physical appearance for some women. The negative relationship between LTPA and functional satisfaction merits further examination, as functional dissatisfaction may motivate individuals to engage in certain types and intensities of LTPA. Correlates of body image differ between appearance and functional satisfaction. Future research should examine appearance and functional satisfaction separately among women with SCI.

More than looking good: impact on quality of life moderates the relationship between functional body image and physical activity in men with SCI.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To examine the relationship between body image and leisure time physical activity (LTPA) among men with spinal cord injury (SCI). Specifically, to examine the moderating function of the perceived impact of body image on quality of life (QOL). SETTING: Ontario, Canada. METHODS: Men with SCI (N=50, 50% paraplegic) reported, (a) their functional and appearance body image (Adult Body Satisfaction Questionnaire), (b) their perceived impact of body image on QOL and (c) LTPA performed over the previous 3 days. RESULTS: Body image was in the 'normal' range compared with the general population. Linear regression analysis found a significant LTPA x body image impact on QOL interaction beta=0.39, P<0.05. Post hoc analysis showed that among individuals who reported a negative effect of body image on QOL, those who engaged in LTPA were less satisfied with their physical function than those who did not. For those who did not perceive their body image to negatively impact their QOL, there was generally no difference in functional body image between those who engaged in LTPA and those who did not. CONCLUSION: Appearance body image is not related to LTPA for men with SCI. It has been suggested that body dissatisfaction may motivate some individuals to engage in LTPA. However, for men living with SCI, functional body image may be associated with LTPA only when a negative effect on QOL is perceived. Future research should consider the moderating function of the perceived impact of body image on QOL when examining the relationship between LTPA and body image among men living with SCI.

Prevalence and treatment of Staphylococcus aureus colonization in patients with mycosis fungoides and Sézary syndrome.

BACKGROUND: Mycosis fungoides (MF) and Sézary syndrome (SS), variants of cutaneous T-cell lymphoma, may arise from antigen-driven clonal expansion and accumulation of helper-memory T cells. Superantigens from Staphylococcus aureus can stimulate T cells. OBJECTIVES: (i) To determine the prevalence of S. aureus carriage in nares and skin in patients with MF/SS compared with historical rates in other conditions. (ii) To determine whether eradication of S. aureus carriage is associated with clinical improvement. Methods Skin and nares cultures were performed prospectively. Patients with positive nares and skin cultures were treated with oral antibiotics and intranasal mupirocin 2% and samples were taken for reculturing at 3 days, 4 weeks and 8 weeks. An exact binomial test was used to compare the carriage rates among different groups. RESULTS: Among 106 patients with MF/SS, 67 (63%) had skin colonization and 57 (54%) had nasal colonization. Staphylococcus aureus was isolated from 44 patients, 33 (31%) each from skin and nares. Colonization was highest in erythrodermic SS (48%), similar to atopic dermatitis (64%), and lowest in MF without erythroderma (26%), psoriasis (21%), and the general population (10%). Oral and topical antibiotics eradicated S. aureus colonization in nares in 28 of 33 (85%) patients and in MF skin lesions in 30 of 33 (91%) patients at 4-8 weeks, with rapid clinical improvement seen in 58% of S. aureus-colonized patients. CONCLUSIONS: Staphylococcal carriage in nares and skin lesions of patients with MF is similar to that in atopic dermatitis. Eradication of staphylococci from the skin is possible with treatment and was associated with clinical improvement.

Forensic isotope analysis to refine a hydrologic conceptual model.

Water resources in the arid southwestern United States are frequently the subject of conflict from competing private and public interests. Legal remedies may remove impasses, but the technical analysis of the problem often determines the future success of legal solutions. In Owens Valley, California, the source of water for the Los Angeles Aqueduct (LAA) is flow diverted from the Owens River and its tributaries and ground water from valley aquifers. Future management of ground water delivered to the LAA needs technical support regarding quantity available, interconnection of shallow and confined aquifers, impact on local springs, and rate of recharge. Ground water flow models and ground water composition are tools already in use, but these have large uncertainty for local interpretations. This study conducted targeted sampling of springs and wells to evaluate the hydrologic system to corroborate conceptual and numerical models. The effort included measurement of intrinsic isotopic composition at key locations in the aquifers. The stable isotopic data of boron (delta(11)B), sulfur (delta(34)S), oxygen (delta(18)O), hydrogen (delta D), and tritium ((3)H) supported by basic chemical data provided rules for characterizing the upper and the lower aquifer system, confirmed the interpretation of ground water flow near faults and flow barriers, and detected hydraulic connections between the LAA and the perennial springs at key locations along the unlined reach of the LAA. This study exemplifies the use of forensic isotopic approaches as independent checks on the consistency of interpretations of conceptual models of a ground water system and the numerical hydrologic simulations.