Dominant heterocyclic composition of dissolved organic nitrogen in the ocean: A new paradigm for cycling and persistence.

Marine dissolved organic nitrogen (DON) is one of the planet's largest reservoirs of fixed N, which persists even in the N-limited oligotrophic surface ocean. The vast majority of the ocean's total DON reservoir is refractory (RDON), primarily composed of low molecular weight (LMW) compounds in the subsurface and deep sea. However, the composition of this major N pool, as well as the reasons for its accumulation and persistence, are not understood. Past characterization of the analytically more tractable, but quantitatively minor, high molecular weight (HMW) DON fraction revealed a functionally simple amide-dominated composition. While extensive work in the past two decades has revealed enormous complexity and structural diversity in LMW dissolved organic carbon, no efforts have specifically targeted LMW nitrogenous molecules. Here, we report the first coupled isotopic and solid-state NMR structural analysis of LMW DON isolated throughout the water column in two ocean basins. Together these results provide a first view into the composition, potential sources, and cycling of this dominant portion of marine DON. Our data indicate that RDON is dominated by 15N-depleted heterocyclic-N structures, entirely distinct from previously characterized HMW material. This fundamentally new view of marine DON composition suggests an important structural control for RDON accumulation and persistence in the ocean. The mechanisms of production, cycling, and removal of these heterocyclic-N-containing compounds now represents a central challenge in our understanding of the ocean's DON reservoir.

Racial disparities in the survival of patients with indolent non-Hodgkin lymphomas in the United States.

There is a paucity of data regarding racial disparities in the survival of patients with indolent non-Hodgkin lymphomas (iNHL) in the contemporary time-period. Hence, we sought to determine whether racial disparities exist in the survival of patients with iNHLs in the US. We included 68 059 adult patients with follicular lymphoma (FL, n = 41 943), marginal zone lymphoma (MZL, n = 22 485), and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM, n = 3631) who were diagnosed in the US between 2000 and 2017. Race was categorized as White, Black, Asian/Pacific Islander, or American Indian/Alaska Native (API/AI). The primary outcome was relative survival (RS), which was estimated using flexible parametric survival models. The RS estimates varied according to race and disease histology but were consistently lower for racial minorities, including those diagnosed during the most recent 5-year time-period of 2012-2017. On multivariable analysis for RS, Black patients with FL had a 32% higher excess mortality rate compared to White patients [adjusted excess hazard ratio (aEHR), 1.32; 95% CI, 1.15-1.51; p < .001], corresponding to a difference of 55 (95% CI, 24-86) excess deaths per 10 000 person-years. For MZL, Black patients had a 40% higher excess mortality rate compared to White patients (aEHR 1.40; 95% CI, 1.18-1.66; p < .001), corresponding to a difference of 62 (95% CI, 26-98) excess deaths per 10 000 person-years. No significant racial differences were detected for patients with WM. The greatest disparity was seen for younger Black patients with FL. Our findings highlight the need for interventions to improve the outcomes of Black patients with iNHLs, particularly younger Black patients with FL.

Implementation of a Pooled Surveillance Testing Program for Asymptomatic SARS-CoV-2 Infections on a College Campus - Duke University, Durham, North Carolina, August 2-October 11, 2020.

On university campuses and in similar congregate environments, surveillance testing of asymptomatic persons is a critical strategy (1,2) for preventing transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). All students at Duke University, a private research university in Durham, North Carolina, signed the Duke Compact (3), agreeing to observe mandatory masking, social distancing, and participation in entry and surveillance testing. The university implemented a five-to-one pooled testing program for SARS-CoV-2 using a quantitative, in-house, laboratory-developed, real-time reverse transcription-polymerase chain reaction (RT-PCR) test (4,5). Pooling of specimens to enable large-scale testing while minimizing use of reagents was pioneered during the human immunodeficiency virus pandemic (6). A similar methodology was adapted for Duke University's asymptomatic testing program. The baseline SARS-CoV-2 testing plan was to distribute tests geospatially and temporally across on- and off-campus student populations. By September 20, 2020, asymptomatic testing was scaled up to testing targets, which include testing for residential undergraduates twice weekly, off-campus undergraduates one to two times per week, and graduate students approximately once weekly. In addition, in response to newly identified positive test results, testing was focused in locations or within cohorts where data suggested an increased risk for transmission. Scale-up over 4 weeks entailed redeploying staff members to prepare 15 campus testing sites for specimen collection, developing information management tools, and repurposing laboratory automation to establish an asymptomatic surveillance system. During August 2-October 11, 68,913 specimens from 10,265 graduate and undergraduate students were tested. Eighty-four specimens were positive for SARS-CoV-2, and 51% were among persons with no symptoms. Testing as a result of contact tracing identified 27.4% of infections. A combination of risk-reduction strategies and frequent surveillance testing likely contributed to a prolonged period of low transmission on campus. These findings highlight the importance of combined testing and contact tracing strategies beyond symptomatic testing, in association with other preventive measures. Pooled testing balances resource availability with supply-chain disruptions, high throughput with high sensitivity, and rapid turnaround with an acceptable workload.

Solid-State 27Al NMR Spectroscopy of the γ-Al13 Keggin Containing Al Coordinated by a Terminal Hydroxyl Ligand.

We report solid-state 27Al NMR spectroscopic results for the sulfate salt of the γ-Al13 Keggin cluster, γ-[AlO4Al12(OH)25(OH2)11][SO4]3·[H2O]14, that provide a spectroscopic signature for partial hydrolysis of this Keggin-type cluster. In 27Al multiple-quantum magic-angle spinning NMR spectra, all 13 Al positions of the cluster are at least partially resolved and assigned with the aid of density functional theory (DFT) calculations of the 27Al electric field gradients. The isotropic chemical shift of the single tetrahedral site, 75.7 ppm, is nearly identical to that reported for solutions from which the cluster crystallizes. Reflecting broadly similar coordination environments, the octahedral Al show mostly small variations in isotropic chemical shift (+7 to +11 ppm) and quadrupolar coupling constant (CQ; 6-7.5 MHz), except for one resonance that exhibits a much smaller CQ and another site with a larger value. DFT calculations show that deprotonation of a terminal water ligand, to form an η-OH group, causes a large reduction in the 27Al CQ, allowing assignment of a distinct, narrow peak for octahedral Al to this hydroxyl-terminated site. This result suggests a relationship between octahedral 27Al NMR line width and hydrolysis for solids prepared from Keggin-type clusters.

Patients' Attitudes Toward Medical Student Participation Across Specialties: A Systematic Review.

UNLABELLED: Phenomenon: Medical students commonly participate in patient care in a variety of different settings. However, a systematic review of patients' attitudes toward medical student participation across specialties has not been performed. APPROACH: The authors searched 7 databases (CINAHL, Cochrane Library, ERIC, MEDLINE, PsycINFO, Scopus, and Web of Science) between January 1, 1999, and August 5, 2014. Two authors independently screened the results and selected articles that were written in English, were published in a peer-reviewed journal, and used a structured or semistructured survey or interview to determine patients' attitudes toward medical student participation in their care. Study quality was assessed using the Medical Education Research Study Quality Instrument. FINDINGS: Fifty-nine studies were included. Average study quality was low. Sixty-one unique evaluation instruments were used, and 34 instruments (56%) lacked validity data. Patient satisfaction was not significantly affected by medical student participation. However, patients' acceptance of medical student participation varied widely between studies and depended on the type of participation. The most common reason for acceptance was a desire to contribute to the education of others, and the most common reason for refusal was concerns about privacy. Minorities were more likely to refuse medical student participation. Patients preferred to be informed before medical students participated in their care. Insights: Patient satisfaction is not significantly affected by medical student participation. However, patient satisfaction may be a poor surrogate marker of patients' acceptance of medical students. Future research should employ validated evaluation instruments to further explore patients' attitudes toward medical student participation.

Optimal aluminum/zirconium: Protein interactions for predicting antiperspirant efficacy using zeta potential measurements.

The interactions between commercial antiperspirant (AP) salts [aluminum chlorohydrate (ACH), activated ACH, aluminum sesquichlorohydrate (ASCH), zirconium aluminum glycine (ZAG), activated ZAG), pure aluminum polyoxocations (Al13-mer, Al30-mer), and the zirconium(IV)-glycine complex Zr6 (O)4 (OH)4 (H2O)8 (Gly)8]12+(-) (CP-2 or ZG) with Bovine serum albumin (BSA) were studied using zeta potential and turbidity measurements. The maximal turbidity, which revealed the optimal interactions between protein and metal salts, for all protein-metal salt samples was observed at the isoelectric point (IEP), where the zeta potential of the solution was zero. Efficacy of AP salts was determined via three parameters: the amount of salt required to flocculate BSA to reach IEP, the turbidity of solution at the IEP, and the pH range over which the turbidity of the solution remains sufficiently high. By comparing active salt performance from this work to traditional prescreening methods, this methodology was able to provide a consistent efficacy assessment for metal actives in APs or in water treatment.

Survival of patients with transformed follicular lymphoma in the United States: a multiple cohort study.

Population-based data comparing the outcomes of patients with transformed follicular lymphoma (t-FL) and de novo diffuse large B-cell lymphoma (DLBCL) are lacking. The objective of this study was to compare the survival of patients with t-FL and de novo DLBCL diagnosed in the United States between 2010-2018. We hypothesized that patients with t-FL would have an inferior survival compared to patients with de novo DLBCL. The study outcomes were relative survival (RS), overall survival (OS), and lymphoma-specific survival (LSS) compared between t-FL and de novo DLBCL. Flexible parametric survival models were used to estimate the study outcomes. There were 569 cases of t-FL and 44,706 cases of de novo DLBCL. Patients with t-FL had an estimated 5-year RS of 54% [95% confidence interval (CI), 49-59%) compared to 67% (95% CI, 66-67%) for those with de novo DLBCL (adjusted hazard ratio, 1.29; 95% CI, 1.11-1.50; P = 0.001). The corresponding 5-year OS estimates were 49% (95% CI, 44-53%) and 57% (95% CI, 57-58%), respectively (adjusted hazard ratio, 1.23; 95% CI, 1.07-1.42; P = 0.004). The corresponding 5-year LSS estimates were 54% (95% CI, 50-59%) and 66% (95% CI, 65-66%), respectively (adjusted hazard ratio, 1.34; 95% CI, 1.15-1.56; P < 0.001). This population-based registry analysis shows that patients with t-FL continue to have an inferior survival in the modern era and should be prioritized for enrollment in clinical trials.

Update on immunizations in adults.

Vaccine-preventable diseases contribute significantly to the morbidity and mortality of U.S. adults. The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention updates its recommended adult immunization schedule annually. The most recent updates include the permissive but not routine use of the quadrivalent human papillomavirus vaccine to prevent genital warts in males; a single dose of herpes zoster vaccine for adults 60 years and older, regardless of their history; replacing a single dose of tetanus and diphtheria toxoids (Td) vaccine with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine in adults 19 years and older who have not previously received Tdap; expanding the indications for pneumococcal polyvalent-23 vaccine to include all adults with asthma and all smokers; annual seasonal influenza vaccination for all adults; and booster doses of meningococcal vaccine for adults with high-risk conditions. It is vital for family physicians to implement a systematic approach to adult immunization that is patient-, staff-, and physician-focused.

Racial and ethnic differences in the utilization of autologous transplantation for lymphoma in the United States.

BACKGROUND: Racial/ethnic disparities in the utilization of hematopoietic cell transplantation (HCT) have been reported for patients with hematologic malignancies, but population-based data are lacking for lymphoma patients. The objective of this study was to determine whether racial and ethnic disparities exist in the utilization of autologous HCT for lymphoma in the United States. METHOD: We used Surveillance, Epidemiology, and End Results data linked to Medicare fee-for-service claims. We included Medicare beneficiaries aged 66+ years with Hodgkin or Non-Hodgkin lymphomas diagnosed between 2008 and 2015. The primary outcome was time-to-autologous HCT. We used Cox proportional hazards models to estimate racial/ethnic differences in utilization. Missing data were handled using multiple imputation with chained equations. RESULTS: We included 40,605 individuals with lymphoma. A total of 452 autologous transplants were performed. In the unadjusted model, Non-Hispanic Black patients were 51% less likely to receive a transplant than Non-Hispanic White patients (95% CI, 0.26-0.96; p = 0.04). After adjusting for age at diagnosis and sex, Non-Hispanic Black patients were 61% less likely to receive a transplant (95% CI, 0.20-0.76; p = 0.01). However, observed differences attenuated and became non-significant after adjustment for socioeconomic factors (adjusted hazard ratio [aHR], 0.62; 95% CI, 0.32-1.21; p = 0.16) and disease-specific factors (aHR, 0.58; 95% CI, 0.30-1.12; p = 0.11), separately. In the fully adjusted model, we also did not observe a statistically significant association between Non-Hispanic Black race/ethnicity and receipt of transplant (aHR, 0.54; 95% CI, 0.28-1.05; p = 0.07). CONCLUSION: In this population-based cohort study of lymphoma patients, Non-Hispanic Black patients were less likely to receive autologous HCT compared to Non-Hispanic White patients, but this difference was partially explained by socioeconomic and disease-specific factors.

Partnerships to Care for Our Patients and Communities During COVID-19.

The Coronavirus disease 2019 (COVID-19) pandemic forced not only rapid changes in how clinical care and educational programs are delivered but also challenged academic medical centers (AMCs) like never before. The pandemic made clear the need to have coordinated action based on shared data and shared resources to meet the needs of patients, learners, and communities. Family medicine departments across the country have been key partners in AMCs' responses. The Duke Department of Family Medicine and Community Health (FMCH) was involved in many aspects of Duke University's and Health System's responses, including leadership contributions in delivering employee health and student health services. The pandemic also surfaced the biological and social interactions that reveal underlying socioeconomic inequalities, for which family medicine has advocated since its inception. Key to success was the department's ability to integrate "horizontally" with the broader community, thereby accelerating the institution's response to the pandemic.

Contribution of amino acid region 659-663 of Factor Va heavy chain to the activity of factor Xa within prothrombinase .

Factor Va, the cofactor of prothrombinase, is composed of heavy and light chains associated noncovalently in the presence of divalent metal ions. The COOH-terminal region of the heavy chain contains acidic amino acid clusters that are important for cofactor activity. In this work, we have investigated the role of amino acid region 659-663, which contains five consecutive acidic amino acid residues, by site-directed mutagenesis. We have generated factor V molecules in which all residues were mutated to either lysine (factor V(5K)) or alanine (factor V(5A)). We have also constructed a mutant molecule with this region deleted (factor V(Δ659-663)). The recombinant molecules along with wild-type factor V (factor V(WT)) were transiently expressed in mammalian cells, purified, and assessed for cofactor activity. Two-stage clotting assays revealed that the mutant molecules had reduced clotting activities compared to that of factor Va(WT). Kinetic analyses of prothrombinase assembled with the mutant molecules demonstrated diminished k(cat) values, while the affinity of all mutant molecules for factor Xa was similar to that for factor Va(WT). Gel electrophoresis analyses of plasma-derived and recombinant mutant prothrombin activation demonstrated delayed cleavage of prothrombin at both Arg(320) and Arg(271) by prothrombinase assembled with the mutant molecules, resulting in meizothrombin lingering throughout the activation process. These results were confirmed after analysis of the cleavage of FPR-meizothrombin. Our findings provide new insights into the structural contribution of the acidic COOH-terminal region of factor Va heavy chain to factor Xa activity within prothrombinase and demonstrate that amino acid region 659-663 from the heavy chain of the cofactor contributes to the regulation of the rate of cleavage of prothrombin by prothrombinase.

Recent survival trends in diffuse large B-cell lymphoma--Have we made any progress beyond rituximab?

BACKGROUND: Population-based studies previously showed an improvement in overall survival (OS) for patients with diffuse large B-cell lymphoma (DLBCL) who received chemoimmunotherapy with rituximab. However, there is limited data (especially at the population level) that show a similar trend in OS improvement, in the most recent time period. We hypothesized that survival for DLBCL patients diagnosed in the United States has continued to improve in recent years and intended to measure outcome improvements. METHODS: Using the SEER-18 registries, we compared the incidence and relative survival rates (RSRs) of DLBCL patients between 2002-2007 and 2008-2013 (availability of novel agents, broader use of autologous hematopoietic cell transplantation and improvement in supportive care). Multivariable Cox regression models were used to assess associations between the year of diagnosis and OS while controlling for age, gender, stage, and ethnicity. RESULTS: There were a total of 53 439 patients with DLBCL who were diagnosed between 2002 and 2013. Of these, 25 810 were diagnosed during time period-1 and 27 629 diagnosed during time period-2. There was a slight decline in incidence of DLBCL (time period-1 vs time period-2), 7.75 (95% CI = 7.66-7.84) vs 7.43 (95% CI = 7.34-7.52) cases per 100 000 persons, respectively (P < .0001). Overall, there was a modest improvement in DLBCL RSRs, with 5-year RSR improving from 61% (time period-1) to 64% (time period-2) and the improvement was noted across all subsets of patients. On multivariable analysis, patients diagnosed in time period-2 had lower mortality relative to time period-1 (HR = 0.87, 95% CI = 0.85-0.89). CONCLUSIONS: Our study shows an improvement in the outcomes of DLBCL patients beyond the introduction of rituximab, although the magnitude of improvement is small. It will be interesting to see the impact of chimeric antigen receptor-T cell therapy translating to population-level survival in the next 5 years.

COVID-19 Severity and Outcomes in Patients With Cancer: A Matched Cohort Study.

PURPOSE: SARS-CoV-2 (COVID-19) is a systemic infection. Patients with cancer are immunocompromised and may be vulnerable to COVID-related morbidity and mortality. The objectives of this study were to determine if patients with cancer have worse outcomes compared with patients without cancer and to identify demographic and clinical predictors of morbidity and mortality among patients with cancer. METHODS: We used data from adult patients who tested positive for COVID-19 and were admitted to two New York-Presbyterian hospitals between March 3 and May 15, 2020. Patients with cancer were matched 1:4 to controls without cancer in terms of age, sex, and number of comorbidities. Using Kaplan-Meier curves and the log-rank test, we compared morbidity (intensive care unit admission and intubation) and mortality outcomes between patients with cancer and controls. Among those with cancer, we identified demographic and clinical predictors of worse outcomes using Cox proportional hazard models. RESULTS: We included 585 patients who were COVID-19 positive, of whom 117 had active malignancy, defined as those receiving cancer-directed therapy or under active surveillance within 6 months of admission. Presenting symptoms and in-hospital complications were similar between the cancer and noncancer groups. Nearly one half of patients with cancer were receiving therapy, and 45% of patients received cytotoxic or immunosuppressive treatment within 90 days of admission. There were no statistically significant differences in morbidity or mortality (P = .894) between patients with and without cancer. CONCLUSION: We observed that patients with COVID-19 and cancer had similar outcomes compared with matched patients without cancer. This finding suggests that a diagnosis of active cancer alone and recent anticancer therapy do not predict worse COVID-19 outcomes and therefore, recommendations to limit cancer-directed therapy must be considered carefully in relation to cancer-specific outcomes and death.

Trends in postrelapse survival in classic Hodgkin lymphoma patients after experiencing therapy failure following auto-HCT.

Patients with classic Hodgkin lymphoma (cHL) who relapse after autologous hematopoietic cell transplantation (auto-HCT) historically have had poor outcomes. We hypothesized that, post-auto-HCT relapse, overall survival (PR-OS) has improved in recent years as a result of more widespread use of novel therapies and allogeneic HCT (allo-HCT). We conducted a retrospective study in 4 US academic centers, evaluating 215 patients who underwent auto-HCT from 2005 to 2016 and relapsed thereafter. Patients were divided into 2 cohorts based on timing of auto-HCT, 2005 through 2010 (cohort 1; n = 118) and 2011 to 2016 (cohort 2; n = 97), to compare differences in clinical outcomes. The median age and disease status at auto-HCT were similar in cohorts 1 and 2. The proportions of patients who received brentuximab vedotin (Bv; 55% vs 69%; P = .07), checkpoint inhibitors (CPIs; 3% vs 36%; P ≤ .001), and allogeneic-HCT (22% vs 35%, P = .03) were significantly different between cohorts 1 and 2, respectively. At the 5-year follow-up after auto relapse, 32% and 50% of patients were alive in cohorts 1 and 2, respectively (P = .01). In multivariate analysis for PR-OS, cohort 1 vs 2 (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.14-4.60; P = .01), age at auto-HCT (HR, 1.48; 95% CI, 1.18-1.87; P ≤ .001), and time to relapse from auto-HCT (HR, 0.59; 95% CI, 0.47-74; P ≤ .0001), retained independent prognostic significance for PR-OS. Our study supports the hypothesis that survival of cHL patients after auto-HCT failure has significantly improved in recent years, most likely because of incorporation of novel therapies and more widespread use of allo-HCT.

Postrelapse survival in diffuse large B-cell lymphoma after therapy failure following autologous transplantation.

Outcomes for diffuse large B-cell lymphoma (DLBCL) patients relapsing after autologous hematopoietic cell transplantation (auto-HCT) have been historically poor. We studied outcomes of such patients using data from 4 transplantation centers. Eligibility criteria included adult patients (age ≥18 years) with DLBCL experiencing disease relapse after auto-HCT performed during 2006 to 2015. The time period was stratified into 2 eras (era 1, 2006-2010; era 2, 2011-2015). The primary end point was postrelapse overall survival (PR-OS). Secondary end points were factors prognostic of PR-OS. Of the 700 patients with DLBCL who underwent auto-HCT, 248 (35%) relapsed after auto-HCT. Median PR-OS of all relapsed DLBCL patients after auto-HCT (n = 228) was 9.8 months (95% confidence interval [CI], 7-15). Median PR-OS was significantly better for patients in complete (17.8 months; 95% CI, 7.9-41.6) vs partial remission at auto-HCT (7.1 months; 95% CI, 5.4-11; P = .01), those undergoing auto-HCT >1 year (12.8 months; 95% CI, 7.6-24.9) vs ≤1 year after DLBCL diagnosis (6.3 months; 95% CI, 4.5-9.2; P = .01), and those with late (56.4 months; 95% CI, 23.7-∞) vs early relapse (5.9 months; 95% CI, 4.5-8.8; P < .0001). On multivariate analysis, although late relapse (hazard ratio [HR], 0.21; 95% CI, 0.13-0.34; P < .0001) was associated with significantly lower mortality, the risk of mortality increased with age (HR, 1.25 per decade; 95% CI, 1.06-1.48; P = .009). This is the largest study to date to evaluate outcomes of DLBCL patients relapsing after auto-HCT. Our study provides benchmarking for future trials of chimeric antigen receptor T cells and other promising agents evaluating PR-OS after auto-HCT.

Multicenter Analysis of Advanced Stage Grade 3A Follicular Lymphoma Outcomes by Frontline Treatment Regimen.

BACKGROUND: Follicular lymphoma (FL) is a common form of non-Hodgkin lymphoma with a wide spectrum of presentation. While grade 1/2 FL is considered low grade and grade 3B FL is approached as an aggressive lymphoma, the management of grade 3A FL remains controversial. PATIENTS AND METHODS: We performed a retrospective, multicenter analysis of patients aged ≥ 18 years with advanced stage 3/4 grade 3A FL diagnosed between January 2006 and July 2016. Patients were stratified by frontline chemotherapy regimen: anthracycline based (ATC), bendamustine (BD), and cyclophosphamide, vincristine, and prednisone (CVP). A total of 103 patients were identified from 6 contributing centers: 65 patients received ATC chemotherapy, 30 BD, and 8 CVP. The primary outcome was time to progression (TTP). Secondary outcomes included progression-free survival, overall survival, complete response rates, large cell transformation, and impact of standardized maximum uptake value on positron emission tomography/computed tomography with outcomes. Patient characteristics were similar among the 3 treatment groups. RESULTS: For TTP at 24 months from initiation of treatment, 72% of ATC, 79% of BD, and 50% of CVP patients had not experienced disease progression (P = .01). Multivariate analysis demonstrated a TTP benefit for ATC compared to CVP (hazard ratio 3.22; 95% confidence interval, 1.26-8.25; P = .01) but no difference when compared to BD. Similar findings were seen with progression-free survival. While overall survival was similar among the 3 arms, there was a higher risk of large cell transformation following BD and CVP. Last, standardized maximum uptake value on positron emission tomography/computed tomography did not affect TTP when comparing BD- and ATC-treated patients. CONCLUSION: Although ATC was superior to CVP, clinical outcomes (TTP, progression-free survival, and overall survival) were similar compared to BD chemotherapy for patients with grade 3A FL.

Detection of toxigenic Clostridium difficile colonization in patients admitted to the hospital for chemotherapy or haematopoietic cell transplantation.

Increasing evidence suggests that asymptomatic carriers are an important source of healthcare-associated Clostridium difficile infection. However, it is not known which test for the detection of C. difficile colonization is most sensitive in patients with haematological malignancies. We performed a prospective cohort study of 101 patients with haematological malignancies who had been admitted to the hospital for scheduled chemotherapy or haematopoietic cell transplantation. Each patient provided a formed stool sample. We compared the performance of five different commercially available assays, using toxigenic culture as the reference method. The prevalence of toxigenic C. difficile colonization as determined by toxigenic culture was 14/101 (14 %). The Cepheid Xpert PCR C. difficile/Epi was the most sensitive test for the detection of toxigenic C. difficile colonization, with 93 % sensitivity and 99 % negative predictive value. Our findings suggest that the Xpert PCR C. difficile/Epi could be used to rule out toxigenic C. difficile colonization in this population.

BRAF V600E expression in histiocytic sarcoma associated with splenic marginal zone lymphoma: a case report.

BACKGROUND: Histiocytic sarcoma is a rare histiocytic neoplasm of unknown etiology that constitutes less than 1% of hematologic malignancies. A few cases of histiocytic sarcoma harboring the BRAF V600E mutation have been reported, but this finding has not been confirmed in all studies. CASE PRESENTATION: We report the case of a 63-year-old white woman with a history of splenic marginal zone lymphoma who presented with 2 weeks of right-sided neck swelling. Positron emission tomography revealed an intensely hypermetabolic and destructive soft tissue mass in her right skull base. A bone marrow biopsy was performed, which revealed an infiltrate of malignant cells characterized as large pleomorphic cells with frequent folded/irregular nuclei, variably prominent nucleoli, fine chromatin, and abundant amounts of eosinophilic cytoplasm. The malignant cells were positive for CD163, CD68 (granular), lysozyme (granular), CD4, and CD45 (partial). Based on the biopsy findings, she was diagnosed as having histiocytic sarcoma. The malignant cells tested positive for the BRAFV600E protein using immunohistochemistry. Before treatment of her histiocytic sarcoma could be initiated, she developed disseminated intravascular coagulation and acute hypoxemic respiratory failure secondary to non-cardiogenic pulmonary edema. She decided to pursue comfort care and died in our hospital 2 weeks following admission. CONCLUSIONS: Our case illustrates the aggressive nature of histiocytic sarcoma, and provides rare evidence that histiocytic sarcoma associated with indolent lymphomas may harbor the BRAF V600E mutation. Further research is needed to clarify the role of targeted therapies such as vemurafenib in the treatment of patients with this disorder.