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BACKGROUND: Clostridium difficile infection (CDI) is one of the most common hospital-acquired infections and is associated with significant morbidity and mortality. Since owning a cat or dog could enrich the gut microbiome, we hypothesized that it would be protective against CDI. AIMS: We conducted a survey study on patients tested for CDI in order to assess whether living in the presence of a pet is associated with a decreased risk of CDI. METHODS: We surveyed subjects aged 18–90 over a 14-month period using a retrospective case–control design. Subjects with CDI were matched by gender and age to patients who tested negative and had no prior history of CDI. A web-based survey was provided to subjects by mail or assisted by phone. Conditional logistic regression was used to assess for associations between CDI and the various risk factors. RESULTS: 205 CDI positive and 205 CDI negative subjects (response rate of 50.2%) were included. After matching for age and sex, living with a cat or dog was not associated with negative CDI testing. Exploratory multivariable modeling identified an unexpected association between positive CDI testing and high meat intake (OR 2.13, 95% CI 1.21–3.77) as well as between positive CDI testing and cat allergies (OR 1.88, 95% CI 1.02–3.46). CONCLUSION: Living with a cat or dog was not associated with negative CDI testing. Several novel risk factors for CDI have been identified including high meat intake and cat allergies.

Infliximab can prevent colectomy in patients hospitalized with acute severe ulcerative colitis (ASUC). In cases of ASUC, fecal losses of infliximab may lead to low drug levels and reduced efficacy. To determine 90-day colectomy risk and postoperative complications in patients receiving single-dose and accelerated induction of infliximab for ASUC. We conducted a retrospective review of patients hospitalized with ASUC requiring infliximab therapy between 2013 and 2017 at the University of Michigan. Patients were excluded if they had an enteric infection, received an anti-TNF previously, or received cyclosporine during the same admission. The primary outcome was colectomy within 90 days of admission. Patients receiving single-dose induction infliximab were compared to those receiving accelerated rescue induction with two doses of infliximab prior to day 14. Administration of accelerated induction was guided by a protocol, suggesting administering a second dose of infliximab to those with only a partial response in CRP 3 days after the initial dose. Postoperative outcomes including 30-day readmission rates and complications were compared using descriptive statistics. From 2013 to 2017, 66 patients with ASUC met our criteria. Thirty-three received accelerated induction (50.0%). The colectomy rate in the accelerated induction group was 30.3% versus 24.2% in the single-dose induction group (p = 0.58). There was no detected difference in postoperative outcomes between the accelerated and single-dose rescue induction. In this retrospective review, 69.7% of those failing to respond to single-dose infliximab were able to avoid colectomy with an accelerated rescue induction strategy without worsening postoperative outcomes. Larger studies of accelerated dosing infliximab are needed.

The purpose of this study is to examine the genetic interaction of variably expressed killer cell immunoglobulin-like receptor (KIR) 3DL1 alleles with their cognate ligand, human leukocyte antigen (HLA)-Bw4, in susceptibility to psoriatic disease (PsD). A novel allelic typing system was developed to differentiate KIR3DL1 alleles (*High, *Low, *Null expression, and 3DS1), in PsD patients, including those with psoriatic arthritis (PsA) and cutaneous psoriasis without arthritis (PsC) and healthy controls. Frequencies of each KIR3DL1 allele, Bw4-80I and Bw4-80T, as well as the genetic interaction between the KIR3DL1 alleles and the Bw4 epitope were analyzed. KIR3DL1 alleles were successfully genotyped in 392 PsA, 260 PsC, and 371 control subjects. Only the KIR3DL1*Null allele was associated with PsD (OR = 0.69, p = 0.008), both in the PsA (OR = 0.69, p = 0.02) and PsC patients (OR = 0.70, p = 0.04) compared to control subjects. No difference in the frequency of KIR3DL1*Null was found between the PsA and PsC patients. The presence of the HLA-Bw4 epitope was significantly associated with PsD, particularly in the PsA patients compared to controls. Bw4-80I was increased in PsD and PsA subjects, but not in PsC patients compared to controls. Bw4-80T was increased in PsA compared to both PsC patients or to controls. No interaction was detected between any of the KIR3DL1 alleles and HLA-Bw4, Bw4-80I, or Bw4-80T. The novel qPCR technique successfully identified the four variably expressed KIR3DL1 alleles. The HLA-Bw4 epitope was associated with psoriatic disease, particularly with PsA, but no genetic interactions with KIR3DL1 alleles were detected.

Three sequential phase II trials were conducted with different immunotherapy approaches to enhance the outcome of autologous transplant (high-dose therapy and autologous stem cell transplantation (HDT/ASCT)) for recurrent follicular lymphoma. Seventy-three patients were enrolled from 1996 to 2009. Patients received HDT/ASCT combined with (1) interferon-α 3 MU/m(2) subcutaneously (SC) three times per week (TIW) for 2 years post-ASCT, (2) rituximab (R) 375 mg/m(2) for in vivo purging 3-5 days pre-stem cell collection and 2 × 4 weekly R at 2 and 6 months post-ASCT, respectively, or (3) three infusions of R pre-stem cell collection followed by 6× R weekly and interferon-α 3 MU/m(2) SC TIW. Although not statistically significant, progression-free survival (PFS) for patients who received rituximab was 56.4 and 49.1% at 5 and 10 years compared to 36 and 21% in those who did not receive rituximab. Molecular relapse post-HDT/ASCT was the strongest predictor of PFS in a multivariate analysis. Molecular relapse was coincident with or preceded clinical relapses in 84% of patients who relapsed—median of 12 months (range 0-129 months). Adverse events included secondary malignancy, transformation to diffuse large B cell lymphoma, prolonged mostly asymptomatic hypogammaglobulinemia, and pulmonary fibrosis. The long-term toxicity profile must be considered when selecting patients for this treatment.

In the pre-rituximab era, transformation of indolent B-cell lymphoma to diffuse large B-cell lymphoma (DLBCL) was associated with an extremely poor outcome and a median post-transformation survival ranging from 1 to 2 years. We evaluated the impact of rituximab-cyclophosphamide, adriamycin, vincristine, prednisone (R-CHOP) on the survival outcomes of transformed lymphoma compared with de novo DLBCL. Between 2002 and 2010, 317 DLBCL patients who were consecutively diagnosed and treated with R-CHOP were identified at our institution. Patients with transformed lymphoma were included if they had not previously received R-CHOP. Patient characteristics, treatment, and outcome data were retrospectively collected. Sixty patients (19 %) had transformed lymphoma of which 37 (62 %) had transformed from follicular lymphoma, 50 (83 %) were chemotherapy naïve, and 58 (96 %) were rituximab naïve at the time of treatment. With a median follow-up of 31.4 months, 231 patients achieved either complete response or complete response unconfirmed (73 %) with no significant difference between de novo DLBCL (n = 192, 75 %) and the transformed group (n = 39, 65 %) (P = 0.25). Six patients (15 %) relapsed in the transformed group at a median time to relapse of 29.3 months. The 2-year and 5-year overall survivals for all patients were 82 and 72 %, respectively. The overall and progression-free survivals for transformed lymphoma and de novo DLBCL were not statistically different (P = 0.45 and P = 0.38, respectively). With R-CHOP chemotherapy, the prognosis of transformed lymphoma in patients with minimal chemotherapy exposure for indolent disease is similar to that of de novo DLBCL.

Twenty-seven subjects with squamous cell cancer of the head and neck received the neoadjuvant IRX-2 immunotherapy regimen prior to surgery in a Phase 2 trial. Pretreatment tumor biopsies were compared with the primary tumor surgical specimens for lymphocyte infiltration, necrosis and fibrosis, using hematoxylin and eosin stain and immunohistochemistry in 25 subjects. Sections were examined by three pathologists. Relative to pretreatment biopsies, increases in lymphocyte infiltration (LI) were seen using H and E or immunohistochemistry. CD3+ CD4+ T cells and CD20+ B cells were primarily found in the peritumoral stroma and CD3+ CD8+ T cells and CD68+ macrophages were mainly intratumoral. LI in the surgical specimens were associated with reductions in the primary tumor size. Improved survival at 5 years was correlated with high overall LI in the tumor specimens. Neoadjuvant IRX-2 immunotherapy regimen may restore immune responsiveness presumably by mobilizing tumor infiltrating effector lymphocytes and macrophages into the tumor.

The matrix protein gene was cloned and sequenced for several recent isolates of avian paramyxovirus type 1 (APMV-1). Specifically, isolates from pigeons and doves, members of the Columbidae family were examined. APMV-1 is the causative agent of Newcastle disease and the virus is associated with disease among a diverse number of avian species. Newcastle disease virus (NDV) isolates from pigeons have also been classified as pigeon paramyxovirus type 1 (PPMV-1). Matrix protein gene sequences for PPMV-1 isolates clustered together as a group relative to isolates from other species phylogenetically. However, there were also isolates from pigeons or doves that grouped with APMV-1 isolates from other species. This indicates that PPMV-1 may be circulating among Columbidae members as a distinct lineage, but that these avian species may also harbor other NDV strains as well. Of particular interest was a dove isolate from Europe that had an aberrant fusion protein cleavage site and was an outlying member phylogenetically between the two major groups of APMV-1 isolates.

The long median survival time of patients with follicular non-Hodgkin's lymphoma (NHL), means that the efficacy of new treatments are difficult to assess in the short term. Bcl-2 is an inhibitor of apoptosis and overexpression of the bcl-2 gene in the blood or bone marrow is a feature in up to 85% of patients with follicular NHL. Levels of bcl-2+ cells in the peripheral blood or bone marrow therefore are a useful measure of disease status in such patients and can be detected by polymerase chain reaction (PCR). Complete bcl-2 clearance from the bone marrow (molecular remission) following autologous stem cell transplant (ASCT) for follicular NHL is considered to be an important prognostic factor for disease-free survival. Tumour cell contamination of the stem cell grafts used in ASCT is commonly associated with relapse. This can be addressed by purging the stem cell harvest prior to transplantation. Various methods of in vitro purging after stem cell collection have been shown to reduce the level of contamination but yield is invariably reduced and grafts remain bcl-2 positive. However, in vivo purging with rituximab during the process of collection has been used to obtain bcl-2-negative stem cell harvests without compromising the yield. Rituximab is a monoclonal antibody licensed for treatment of relapsed and refractory low-grade or follicular NHL. Rituximab targets the CD20 antigen, which is found on cells of the B cell lineage. When used for in vivo purging it depletes the peripheral blood of CD20-positive cells and prevents contamination by lymphoma cells. Molecular remission, as measured by bone-marrow bcl-2 clearance, has been achieved in 7/7 patients with follicular NHL at 1 year after treatment with ASCT using rituximab as an ‘in vivopurse’, followed by rituximab maintenance. Early clinical outcomes are also encouraging. Bone Marrow Transplantation (2002) 29, Suppl. 1, S14–S17. doi:10.1038/sj.bmt.1703297

Natural attenuation of ALVAC virus in mammals makes it an attractive vector for cancer vaccine therapy of immunocompromised hosts, such as patients with lymphoid malignancies. However, the transduction efficiency of ALVAC constructs in lymphoid tumors has not yet been characterized. We studied a wide spectrum of human T- and B-cell leukemia and lymphomas and found significant heterogeneity of the ALVAC-mediated gene product expression in these tumors. While ALVAC-B7.1, ALVAC-B7.2, or ALVAC-luciferase vectors effectively expressed recombinant genes in malignancies arising from T- or early B-cell precursors, negative or low expression of ALVAC recombinant genes occurred in tumors arising from mature B-cells. We showed that ALVAC-encoded B7.1 or B7.2 was continuously expressed on the infected, and subsequently irradiated, leukemia cells, and only cells with ALVAC-mediated expression of costimulatory molecules (but not unmodified leukemia cells or those infected with the ALVAC-parental vector) induced significant proliferation and IFN-gamma production by alloreactive T-cells. These data provide the rationale for clinical studies using the ALVAC vector system for gene transfer into lymphoid tumors of T- and early B-cell origin to render them more immunogenic, while alternative strategies should be considered for immunotherapy of mature B-cell malignancies.

Several nonrandom chromosomal translocations that occur in T and B cell malignancy have been shown to involve the juxtaposition of a putative proto-oncogene and one of the antigen receptor genes. Cloning studies of several of these breakpoints have helped to elucidate the structural basis of some of these chromosomal translocations as well as the molecular characteristics of some of the proto-oncogenes. One of the most studied proto-oncogenes is BCL2, frequently involved in a translocation in B cell lymphomas. Several biological studies of the expression of this proto-oncogene in cell lines and/or transgenic mice have shown that it is one of the factors which can induce lymphoid proliferation and may thus be an important etiologic factor in the generation of B cell lymphoma. Cloning studies of these chromosomal breakpoints have led to the application of molecular genetic techniques for the diagnosis and detection of expression of these proto-oncogenes. Further study of these oncogenes is required to establish their role in tumorigenesis and their usefulness in clinical practice.