Thyroblastoma in a rhesus macaque (Macaca mulatta): A case report.

In this report, we describe the gross, histopathology, and immunohistochemical findings of a thyroblastoma that arose in the right lobe of the thyroid gland in a 2-month-old rhesus macaque (Macaca mulatta).

Isotope-specific reactions of acetonitrile (CH3CN) with trapped, translationally cold CCl.

The gas-phase reaction of CCl+ with acetonitrile (CH3CN) is studied using a linear Paul ion trap coupled to a time-of-flight mass spectrometer. This work builds on a previous study of the reaction of CCl+ with acetylene [K. J. Catani et al., J. Chem. Phys. 152, 234310 (2020)] and further explores the reactivity of CCl+ with organic neutral molecules. Both of the reactant species are relevant in observations and models of chemistry in the interstellar medium. Nitriles, in particular, are noted for their relevance in prebiotic chemistry and are found in the atmosphere of Titan, one of Saturn's moons. This work represents one of the first studied reactions of a halogenated carbocation with a nitrile and the first exploration of CCl+ with a nitrile. Reactant isotopologues are used to unambiguously assign ionic primary products from this reaction: HNCCl+ and C2H3 +. Branching ratios are measured, and both primary products are determined to be equally probable. Quantum chemical and statistical reaction rate theory calculations illuminate pertinent information for interpreting the reaction data, including reaction thermodynamics and a potential energy surface for the reaction, as well as rate constants and branching ratios for the observed products. In particular, the reaction products and potential energy surface stimulate questions regarding the strength and role of the nitrile functional group, which can be further explored with more reactions of this class.

Isomer-selected ion-molecule reactions of acetylene cations with propyne and allene.

One of the fundamental goals of chemistry is to determine how molecular structure influences interactions and leads to different reaction products. Studies of isomer-selected and resolved chemical reactions can shed light directly on how form leads to function. In the following, we present the results of gas-phase reactions between acetylene cations (C2D2+) with two different isomers of C3H4: propyne (DC3D3) and allene (H2C3H2). Our highly controlled, trapped-ion environment allows for precise determination of reaction products and kinetics. From these results, we can infer details of the underlying reaction dynamics of C2H2+ + C3H4. Through the synergy of experimental results and high-level quantum chemical potential energy surface calculations, we are able to identify distinct reaction mechanisms for the two isomers. We find long-range charge exchange with no complex formation is favored for allene, whereas charge exchange leads to an intermediate reaction complex for propyne and thus, different products. Therefore, this reaction displays a pronounced isomer-selective bi-molecular reactive process.

Reactions of translationally cold trapped CCl+ with acetylene (C2H2).

Ion-neutral chemical reactions are important in several areas of chemistry, including in some regions of the interstellar medium, planetary atmospheres, and comets. Reactions of CCl+ with C2H2 are measured, and the main products include C3H2 + and C3H+, both relevant in extraterrestrial environments. Accurate branching ratios are obtained, which favor the formation of C3H2 + over C3H+ by a factor of four. The measured rate constants are on the order of Langevin, and complementary electronic structure calculations are used to aid in the interpretation of experimental results.

The National Psoriasis Foundation psoriasis treatment targets in real-world patients: prevalence and association with patient-reported outcomes in the Corrona Psoriasis Registry.

INTRODUCTION: The National Psoriasis Foundation (NPF) published treat-to-target guidelines for psoriasis, yet their applicability in clinical practice remains unknown. OBJECTIVES: To estimate the proportion of psoriasis patients meeting the NPF's body surface area (BSA) 'target' (≤1%) and 'acceptable' (≤3%) response criteria and the cross-sectional associations of these criteria with patient-reported outcomes (PROs) in the Corrona Psoriasis Registry. METHODS: Separately for three independent cross-sectional cohorts of patients at the (i) enrolment, (ii) 6-month and (iii) 12-month visits, we calculated the proportion of patients with BSA ≤1% and ≤3%. Furthermore, we calculated odds ratios estimating the risk of PROs associated with not meeting criteria in the 6-month cohort. RESULTS: The enrolment, 6- and 12-month cohorts included 2794, 1310 and 629 patients, respectively. At enrolment, 24% of patients had a BSA ≤ 1% and 41% a BSA ≤ 3%. In the 6-month cohort, 43%/64% had a BSA ≤ 1%/BSA ≤ 3%. In the 12-month cohort, 46%/69% of patients had a BSA ≤ 1%/BSA ≤ 3%. Patients not at target/acceptable criteria had higher odds for worse quality of life compared with those who were. CONCLUSION: While most patients at 6- and 12-month visits were at the 'acceptable' response, less than half were at the 'target' response despite systemic therapy. There remain unmet needs to optimize psoriasis therapy and further validate current treat-to-target guidelines.

Utilization of the validated Psoriasis Epidemiology Screening Tool to identify signs and symptoms of psoriatic arthritis among those with psoriasis: a cross-sectional analysis from the US-based Corrona Psoriasis Registry.

BACKGROUND: Despite increasing awareness of the disease, rates of undiagnosed psoriatic arthritis (PsA) are high in patients with psoriasis (PsO). The validated Psoriasis Epidemiology Screening Tool (PEST) is a five-item questionnaire developed to help identify PsA at an early stage. OBJECTIVES: To assess the risk of possible undiagnosed PsA among patients with PsO and characterize patients based on PEST scores. METHODS: This study included all patients enrolled in the Corrona PsO Registry with data on all five PEST questions. Demographics, clinical characteristics and patient-reported outcomes were compared in Corrona PsO Registry patients with PEST scores ≥3 and <3 using t-tests for continuous variables and chi-squared tests for categorical variables; scores ≥3 may indicate PsA. RESULTS: Of 1516 patients with PsO, 904 did not have dermatologist-reported PsA; 112 of these 904 patients (12.4%) scored ≥3 and were significantly older, female, less likely to be working, and had higher BMI than patients with scores <3. They also had significantly longer PsO duration, were more likely to have nail PsO and had worse health status, pain, fatigue, Dermatology Life Quality Index and activity impairment. CONCLUSIONS: Improved PsA screening is needed in patients with PsO because the validated PEST identified over one-tenth of registry patients who were not noted to have PsA as having scores ≥3, who could have had undiagnosed PsA. Appropriate, earlier care is important because these patients were more likely to have nail PsO, worse health-related quality of life and worse activity impairment.

Medication use by adolescents and adults with fragile X syndrome.

BACKGROUND: The behavioural challenges and medical conditions associated with fragile X syndrome (FXS) can lead to increased need for medications. METHOD: This longitudinal study examined the use of prescription medications for psychotropic and non-psychotropic purposes by adolescents and adults with FXS drawn from a North American community sample (N = 105). Odds and probabilities of continuing or discontinuing medication were calculated. Predictors of medication use were calculated. RESULTS: More than two-thirds took psychotropic medication, and about one-quarter took non-psychotropic medication. Over a 3-year period, those who initially took prescription medications were considerably more likely to remain on medications than to stop. Individuals with more autism symptoms, more behavioural problems, a mental health diagnosis, and greater family income were significantly more likely to use psychotropic medication 3 years later. Individuals who had more health problems, a mental health diagnosis, and were female were more likely to use non-psychotropic medication over this time period. CONCLUSIONS: Findings highlight the elevated and ongoing use of medication by individuals with FXS. Implications for social and behavioural research on FXS are discussed.

Estimating community-level costs of preterm birth.

OBJECTIVES: To develop generalizable methods for estimating the economic impact of preterm birth at the community level on initial hospital expenditures, educational attainment and lost earnings as well as to estimate potential savings associated with reductions in preterm birth. STUDY DESIGN: The retrospective, population-based analysis used vital statistics and population demographics from Hamilton County, Ohio, USA, in 2012. METHODS: We adjusted previously reported, mean initial hospital cost estimates (stratified by each week of gestation) to 2012 dollars using national cost-to-charge ratios. Next, we calculated excess costs attributable to prematurity and potential hospital cost savings, which could be realized by prolonging each preterm pregnancy by a single week of gestation. Using reported associations among preterm birth, educational attainment and adult earnings, we developed generalizable formulas to calculate lost academic degrees and lost income estimates attributable to preterm birth. The formulas generated estimates based on local population demographics. RESULTS: The annual initial hospital cost associated with 1444 preterm infants was estimated at $93 million. In addition, over 9000 fewer college degrees and over $300 million in lost annual earnings were attributed to local adults who were born preterm. Prolonging each preterm birth by 1 week could potentially reduce initial hospital expenditures by over $25 million. Additional potential savings could be realized as healthier infants attain higher levels of education and earnings as adults. CONCLUSIONS: The generalizable methods developed for estimating the economic impact of preterm birth at the community level can be used by any community in which vital statistics and population demographics are available. Cost estimates can serve to rally support for local stakeholder investment in developing strategies for preterm birth intervention leading to improved pregnancy outcomes.

Plasma levels of interleukin-1 receptor antagonist (IL1Ra) predict radiographic progression of symptomatic knee osteoarthritis.

OBJECTIVE: Pro- and anti-inflammatory mediators, such as IL-1ß and IL1Ra, are produced by joint tissues in osteoarthritis (OA), where they may contribute to pathogenesis. We examined whether inflammatory events occurring within joints are reflected in plasma of patients with symptomatic knee osteoarthritis (SKOA). DESIGN: 111 SKOA subjects with medial disease completed a 24-month prospective study of clinical and radiographic progression, with clinical assessment and specimen collection at 6-month intervals. The plasma biochemical marker IL1Ra was assessed at baseline and 18 months; other plasma biochemical markers were assessed only at 18 months, including IL-1ß, TNFα, VEGF, IL-6, IL-6Rα, IL-17A, IL-17A/F, IL-17F, CRP, sTNF-RII, and MMP-2. RESULTS: In cross-sectional studies, WOMAC (total, pain, function) and plasma IL1Ra were modestly associated with radiographic severity after adjustment for age, gender and body mass index (BMI). In addition, elevation of plasma IL1Ra predicted joint space narrowing (JSN) at 24 months. BMI did associate with progression in some but not all analyses. Causal graph analysis indicated a positive association of IL1Ra with JSN; an interaction between IL1Ra and BMI suggested either that BMI influences IL1Ra or that a hidden confounder influences both BMI and IL1Ra. Other protein biomarkers examined in this study did not associate with radiographic progression or severity. CONCLUSIONS: Plasma levels of IL1Ra were modestly associated with the severity and progression of SKOA in a causal fashion, independent of other risk factors. The findings may be useful in the search for prognostic biomarkers and development of disease-modifying OA drugs.

Prior infections are associated with increased mortality from subsequent blood-stream infections among patients with hematological malignancies.

Many patients who are evaluated and treated for sepsis have histories of recent infections. The prognostic implications of surviving an infectious process are not well understood. We undertook this study to determine the clinical impact of prior infections among patients with hematological malignancies, a population at high risk for developing and dying from sepsis. The medical records of 203 patients with hematological malignancies and blood-stream infections admitted over a 3-year period to an urban teaching hospital were retrospectively reviewed. The 30-day mortality after blood-stream infection in these high-risk patients was 24 %. There were 46 patients (23 %) who had inpatient infections in the 90 days prior to the index blood-stream infection. History of recent infection portended worse prognosis from blood-stream infection under multivariable analysis [odds ratio (OR) 2.60, p = 0.04, 95 % confidence interval (CI) 1.04-6.47]. There were 86 patients (42 %) who had subsequent infections in the first 90 days after the index blood-stream infection. Patients with subsequent infections had greater mortality during days 91-365 than patients without subsequent infections [hazard ratio (HR) 1.97, p = 0.02, 95 % CI 1.13-3.44]. Recent infections prognosticate worse outcomes from subsequent blood-stream infections for this high-risk population. Further research into the clinical and biochemical reasons for this observation may lead to targets for intervention, and, ultimately, improvements in long-term mortality from sepsis.

Evaluation of seasonal feeding patterns of West Nile virus vectors in Bernalillo county, New Mexico, United States: implications for disease transmission.

Many mosquito species take bloodmeals predominantly from either birds or mammals. Other mosquito species are less host-specific and feed readily on both. Furthermore, some species tend to alter their feeding patterns over the course of the year; early in the mosquito season such species may feed primarily on a particular host type, and subsequently take an increasingly larger proportion of their bloodmeals from an alternative host type as the season progresses. We have examined the feeding patterns of the three mosquito species found in Bernalillo County, NM: Culex quinquefasciatus (Say), Culex tarsalis (Coquillett), and Aedes vexans (Meigen). Specifically, we seek to determine if any of these species displays a seasonal shift in terms of its host utilization pattern. Our analysis focuses on these three species because they are all considered to be competent vectors for the West Nile virus (WNV). Our current data for Cx. quinquefasciatus suggest that unlike elsewhere in its range, this species increases its proportion of avian bloodmeals as the season progresses. Alternatively, Ae. vexans feeds primarily on mammals, whereas Cx. tarsalis appears to feed on both mammals and birds throughout the mosquito season. A more complete understanding of the feeding habits of these three mosquito species may help to clarify the transmission dynamics of WNV in Bernalillo County.

Improved efficiency and safety for EVAR with utilization of a hybrid room.

OBJECTIVE: Access to a hybrid endovascular suite is touted as a necessity for advanced endovascular aneurysm repair (EVAR) to improve imaging accuracy and safety. Yet there remain little data documenting this intuitive advantage of a hybrid setup versus a traditional operating room (OR) utilizing a portable fluoroscopic unit (C-arm) for imaging. We hypothesized that standard elective EVAR performed in a hybrid suite would improve procedural efficiency and accuracy, as well minimize patient exposure to both contrast and radiation. METHODS: We retrospectively reviewed a single attending surgeon's EVAR practice, which encompassed the transition to a hybrid endovascular suite (opened July 2010). Only consecutive abdominal aneurysms were included in the analysis to attempt to create a homogenous cohort. All emergent, aorto-uni-iliac (AUI), snorkel, fenestrated, or hybrid procedures were excluded. Standard variables evaluated and compared between the two study subgroups included fluoroscopy time, operative time, contrast use, stent-graft component utilization, complication rates, and short-term endoleaks. RESULTS: From January 2008 to August 2012, we performed 213 EVAR procedures for abdominal aortic aneurysms. After excluding emergent, AUI, snorkel, or hybrid procedures, we analyzed 109 routine EVARs. Fifty-eight consecutive cases were done in the OR with a C-arm until July 2010, and the last 51 cases were done in the hybrid room. Both groups were well matched in terms of demographics, aneurysm morphology, and procedural characteristics. No difference was found in terms of complication rates or operative mortality, although there was a trend towards decreased fluoroscopy time, type I/III endoleaks, and a number of additional endograft components utilized. Compared with patients repaired in the OR/C-arm, EVAR done in the hybrid room resulted in less total OR time and contrast usage (p < .05). CONCLUSIONS: Routine EVAR performed in a hybrid fixed-imaging suite affords greater efficiency and less harmful exposure of contrast and possible radiation to the patient. Accurate imaging quality and deployment is associated with less need for additional endograft components, which should lead to improved cost efficiency. Confirmation of these findings might be necessary in a randomized control trial to fully justify the capital expenditure necessary for hybrid endovascular suites.

Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA.

OBJECTIVE: The study aimed determining whether assessment of cartilage oligomeric matrix protein (COMP) degradation products could serve as a serological disease course and therapeutic response predictor in arthritis. METHODS: We generated a panel of monoclonal antibodies against COMP fragments and developed a novel capture enzyme-linked immunosorbent assay (ELISA) for detecting COMP fragments in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). This test was also used to monitor COMP fragments in surgically-induced OA, collagen-induced arthritis (CIA), and tumor necrosis factor (TNF) transgenic animal models. RESULTS: Compared with a commercial COMP ELISA kit that detected no significant difference in COMP levels between OA and control groups, a significant increase of the COMP fragments were noted in the serum of OA patients assayed by this newly established ELISA. In addition, serum COMP fragment levels were well correlated with severity in OA patients and the progression of surgically-induced OA in murine models. Furthermore, the serum levels of COMP fragments in RA patients, mice with CIA, and TNF transgenic mice were significantly higher when compared with their controls. Interestingly, treatment with TNFα inhibitors and methotrexate led to a significant decrease of serum COMP fragments in RA patients. Additionally, administration of Atsttrin [Tang, et al., Science 2011;332(6028):478] also resulted in a significant reduction in COMP fragments in arthritis mice models. CONCLUSION: A novel sandwich ELISA is capable of reproducibly measuring serum COMP fragments in both arthritic patients and rodent arthritis models. This test also provides a valuable means to utilize serum COMP fragments for monitoring the effects of interventions in arthritis.

Behaviour problems, maternal internalising symptoms and family relations in families of adolescents and adults with fragile X syndrome.

BACKGROUND: Studies have linked the behaviour problems of children with fragile X syndrome (FXS) to maternal well-being, but less is known about how behaviour problems relate to important family factors such as marital satisfaction and family cohesion. METHODS: Married mothers of 115 adolescents and adults with FXS completed questionnaires and interviews, and maternal CGG repeat length was obtained by medical/laboratory records or by blood analysis. RESULTS: Indirect effects were present between behaviour problems and family variables in that behaviour problems were positively related to maternal internalising symptoms which were, in turn, negatively associated with both family cohesion and marital satisfaction. Direct associations between behaviour problems and family relationship variables were not significant. CONCLUSIONS: Findings suggest the importance of intervening with behaviour problems in individuals with FXS and identify maternal mental health as a potentially powerful conduit for the effects of child behaviour on relationships within these families. Implications for targeted interventions are discussed.

Multi-disciplinary assessment of the entrustable professional activities of surgery residents.

Purpose: Medicine is practiced in a collaborative and interdisciplinary manner. However, medical training and assessment remain largely isolated in traditional departmental silos. Two Entrustable Professional Activities (EPAs) developed by the American Board of Surgery are multidisciplinary in nature and offer a unique opportunity to study interdisciplinary assessment. Methods: EPA microassessments were collected from Surgery and Emergency Medicine (EM) faculty between July 2018 and May 2020. Differences in feedback provided by faculty were assessed using natural language processing (NLP) techniques, (1) automated algorithms; and (2) topic modeling. Summative content analysis was used to identify themes in text feedback. We developed automated coding algorithms for these themes using regular expressions. Topic modeling was performed using latent Dirichlet allocation. Results: 549 assessments were collected for two EPAs: 198 for GS Consultation and 351 for Trauma. 27 EM and 27 Surgery faculty provided assessments for 71 residents. EM faculty were significantly more likely than Surgery faculty to submit feedback coded as Communication, Demeanor, and Timeliness, (all chi-square test p-values < 0.01). No significant differences were found for Clinical Performance, Skill Level, or Areas for Improvement. Similarly, topic modeling indicated that assessments submitted by EM faculty focused on communication, timeliness, and interpersonal skills, while those submitted by Surgery faculty focused on the residents' abilities to effectively gather information and correctly diagnose the underlying pathology. Conclusions: Feedback from EM and Surgery faculty differed significantly based on NLP analyses. EPA assessments should stem from multiple sources to avoid assessment gaps and represent a more holistic picture of performance.

Use of bidirectional barbed suture in laparoscopic myomectomy: evaluation of perioperative outcomes, safety, and efficacy.

STUDY OBJECTIVE: To compare perioperative outcomes during laparoscopic myomectomy using a bidirectional barbed suture vs conventional smooth suture. DESIGN: Retrospective analysis of 138 consecutive laparoscopic myomectomies performed by a single surgeon over 3 years (Canadian Task Force classification II-2). SETTING: Major university teaching hospital. PATIENTS: One hundred thirty-eight women with symptomatic uterine myomas. INTERVENTIONS: In women undergoing laparoscopic myomectomy from February 2007 through April 2010, conventional smooth sutures were used in 31 patients, and bidirectional barbed suture in 107 patients. MEASUREMENTS AND MAIN RESULTS: The primary indications for laparoscopic myomectomy in either group were pelvic pain or pressure and abnormal uterine bleeding. Use of bidirectional barbed suture was found to significantly shorten the mean (SD) duration of surgery (118 [53] minutes vs 162 [69] minutes; p <.05) and reduce the duration of hospital stay (0.58 [0.46] days vs 0.97 [0.45] days; p <.05). No significant differences were observed between the 2 groups insofar as incidence of perioperative complications, estimated blood loss, and number or weight of myomas removed during surgery. CONCLUSION: Use of bidirectional barbed suture seems to facilitate closure of the hysterotomy site in laparoscopic myomectomy.

Current practice patterns for initial umbilical hernia repair in the United States.

PURPOSE: The approach to repairing an initial umbilical hernia (IUH) varies substantially, and this likely depends on hernia size, patient age, sex, BMI, comorbidities including diabetes mellitus, and surgeon preference. Of these, only hernia size has been widely studied. This cross-sectional study aims to look at the practice pattern of umbilical hernia repair in the United States. METHODS: A retrospective study was performed using data from the America Hernia Society Quality Collaborative. Patient characteristics included age, sex, hernia width, BMI, smoking status, and diabetes. Outcomes were use of mesh for repair, as well as surgical approach (open vs minimally invasive). Multivariate logistic regression was performed to assess the independent effect of age, sex, hernia width, BMI, smoking status, and diabetes on use of mesh and approach to repair. RESULTS: 3475 patients were included. 74% were men. Mesh use was more common in men (67% vs 60%, P < 0.001). Mesh was used in 33% of repairs ≤ 1 cm, and 82% of repairs > 1 cm (P < 0.001). Younger patients were less likely to receive a mesh repair (54% if age ≤ 35 vs 67% for age > 35, P < 0.001). However, on multivariate analysis, mesh use was associated with increasing hernia width (OR 5.474, 95% CI 4.7-6.3) as well as BMI (OR 1.8, 95% CI 1.5-2.1) but not with age or sex. CONCLUSION: The majority of IUH are performed open. Patient BMI and hernia defect size contribute to choice of surgical technique including use of mesh. The use of mesh in 33% of hernias below 1 cm demonstrates a gap between evidence and practice. Patient factors including patient age and sex had no impact on operative approach or use of mesh.

Mechanisms of idiotype suppression. IV. Functional neutralization in mixtures of idiotype-specific suppressor and hapten-specific suppressor T cells.

Specific tolerance to phosphorylcholine (PC) can be induced in BALB/c mice by neonatal injection with either pneumococcal C-polysaccharide (PnC) or anti-TEPC 15 idiotype (T15Id) antibody specific for the major idiotype (Id) of anti-PC antibody. Spleen cells from these tolerant mice exhibited T cell-mediated active suppression of anti-PC response when they were co-cultured with normal spleen cells. Suppressor cells from the PnC-injected mice appeared to bear either Lyt-1 or Lyt-2 antigens, whereas suppressor cells from anti-Id-treated mice expressed Lyt-2 antigens. Analyses of the specific receptors of these suppressor T cells, based on either adherence to PC and T15-coated petri dishes or cytolysis by rabbit anti-T15Id and monoclonal IgM anti-PC antibody with complement, revealed that receptors of PnC-induced suppressor T cells recognize PC, whereas receptors of anti-Id-induced suppressor T cells react with the T15Id. The possible interaction of the two different types of suppressor T cells was examined by co-culturing normal spleen cells with mixtures of the different suppressor cell types in various cell ratios in the presence of the T-independent PC-antigen, R36a. A brief incubation of anti-Id-induced, T15Id-specific suppressor T cells with PnC-induced, hapten-specific, and T15Id-bearing suppressor T cells resulted in complete cancellation of their suppressor function. These results suggest that idiotype network regulation may also occur among suppressor T cell population.

Mature T-lineage leukemia with growth factor-induced multilineage differentiation.

We report an acute T-lymphoblastic leukemia with a predominantly mature CD3+ CD7+ WT31+ phenotype that was induced to differentiate into different cell lineages by various recombinant human growth factors. In the presence of IL-3 or GM-CSF, the leukemic cells gave rise to myeloid and monocytic cells including terminally differentiated, partially functional, segmented neutrophilic granulocytes as assessed by morphologic, cytochemical, immunophenotypic, and functional criteria. In the presence of IL-2, leukemic granulated lymphoid cells exhibiting MHC-unrestricted cytotoxicity and expressing a CD2+ CD3+ CD5+ CD7+ CD8+ CD33+ WT31+ Leu19+ phenotype arose. Leukemic cell cultures initiated with IL-3 yielded growth factor-independent cells with a mixed lineage phenotype and morphologic and cytochemical evidence of immature blasts. These were T lymphocyte and myeloid surface antigen (CD2,CD3,CD5,CD7,CD13,CD33,WT31) positive. Identical rearrangements of the constant region of the TCR-delta gene and of the joining regions of the TCR-beta, -gamma, and -delta genes were observed in the fresh and all cultured leukemic cells, indicating that they were derived from the same malignant clone. Consistent with the molecular genetic data, the cytogenetic analyses of the GM-CSF-, IL-3-cultured and the growth factor-independent leukemic cells showed the presence of multiple, closely related abnormal clones, all of which had an interstitial deletion of part of the long arm of chromosome 6 and a complex 1;10;12 translocation. In conclusion, these data demonstrate the involvement of a multipotent leukemic precursor cell in this predominantly mature CD2+ CD3+ CD5+ CD7+ WT31+ T-ALL. This multipotent leukemic precursor may be susceptible to various growth factors and respond with ordered differentiation and maturation.

Association of methotrexate and tumour necrosis factor antagonists with risk of infectious outcomes including opportunistic infections in the CORRONA registry.

OBJECTIVE: To examine the association of methotrexate (MTX) and tumour necrosis factor (TNF) antagonists with the risk of infectious outcomes including opportunistic infections in patients with rheumatoid arthritis (RA). METHODS: Patients with RA enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) registry prescribed MTX, TNF antagonists or other disease-modifying antirheumatic drugs (DMARDs) were included. The primary outcomes were incident overall and opportunistic infections. Incident rate ratios were calculated using generalised estimating equation Poisson regression models adjusted for demographics, comorbidities and RA disease activity measures. RESULTS: A total of 7971 patients with RA were followed. The adjusted rate of infections per 100 person-years was increased among users of MTX (30.9, 95% CI 29.2 to 32.7), TNF antagonists (40.1, 95% CI 37.0 to 43.4) and a combination of MTX and TNF antagonists (37.1, 95% CI 34.9 to 39.3) compared with users of other non-biological DMARDs (24.5, 95% CI 21.8 to 27.5). The adjusted incidence rate ratio (IRR) was increased in patients treated with MTX (IRR 1.30, 95% CI 1.12 to 1.50) and TNF antagonists (IRR 1.52, 95% CI 1.30 to 1.78) compared with those treated with other DMARDs. TNF antagonist use was associated with an increased risk of opportunistic infections (IRR 1.67, 95% CI 0.95 to 2.94). Prednisone use was associated with an increased risk of opportunistic infections (IRR 1.63, 95% CI 1.20 to 2.21) and an increased risk of overall infection at doses >10 mg daily (IRR 1.30, 95% CI 1.11 to 1.53). CONCLUSIONS: MTX, TNF antagonists and prednisone at doses >10 mg daily were associated with increased risks of overall infections. Low-dose prednisone and TNF antagonists (but not MTX) increased the risk of opportunistic infections.