Hodgkin's lymphoma of the uterus presenting as refractory pelvic inflammatory disease. A case report

Lymphoma rarely presents with initial involvement of the uterine corpus, though disseminated disease may well involve the pelvic organs secondarily. We treated a patient for Hodgkin's lymphoma presenting as pelvic serositis found at hysterectomy for refractory pelvic pain. Nodules consistent with Hodgkin's lymphoma were found within the uterine serosa and muscularis as well as throughout the uterine and tubal lymphatics, but no visible or palpable adenopathy was noted in the pelvis or abdomen or peripherally. Following surgery the patient developed signs and symptoms of widespread lymphoma, which developed fulminantly but responded well initially to standard chemotherapy. This is the first reported case of systemic Hodgkin's lymphoma presenting de novo in the uterine corpus and associated with clinical symptoms referable to the female reproductive tract.     

Diffusion tensor imaging of articular cartilage as a measure of tissue microstructure

OBJECTIVE: To use diffusion tensor MR micro-imaging to observe differences in magnitude and anisotropy of water diffusion between 'healthy' cartilage and cartilage enzymatically degraded to simulate arthritic damage. METHODS: Diffusion tensor images (156 x 156 microm in-plane resolution, 2mm slice thickness) of bovine cartilage were obtained at either 4.7 or 7.0 T using pulsed field gradient spin echo sequences. The parameters determined were: maximum and mean diffusivity, direction of the maximum diffusion eigenvector with respect to the normal to the articular surface and fractional anisotropy (FA) of diffusion. RESULTS: Both maximum and mean diffusion eigenvalues were found to decrease, respectively, from approximately 1.95 x 10(-9) and 1.80 x 10(-9) m2 s(-1) at the articular surface to approximately 1.08 x 10(-9) and 0.79 x 10(-9) m2 s(-1) in the deep zone. A systematic change was observed in the direction of the eigenvector corresponding to maximum diffusivity, reflecting the expected change in orientation of the collagen macrofibrillar bundles. Degradation with trypsin to remove proteoglycans resulted in a 10-15% increase in apparent diffusion coefficient of water in the cartilage, with no apparent change in FA. CONCLUSIONS: These methods have the potential to be used to probe local changes in tissue microstructure and the hydrodynamic status of cartilage during development of osteoarthritis.     

Structure-based design and discovery of protein tyrosine phosphatase inhibitors incorporating novel isothiazolidinone heterocyclic phosphotyrosine mimetics

Structure-based design led to the discovery of novel (S)-isothiazolidinone ((S)-IZD) heterocyclic phosphotyrosine (pTyr) mimetics that when incorporated into dipeptides are exceptionally potent, competitive, and reversible inhibitors of protein tyrosine phosphatase 1B (PTP1B). The crystal structure of PTP1B in complex with our most potent inhibitor 12 revealed that the (S)-IZD heterocycle interacts extensively with the phosphate binding loop precisely as designed in silico. Our data provide strong evidence that the (S)-IZD is the most potent pTyr mimetic reported to date.     

The lack of correlation between radiographic findings and cartilage integrity

Total knee arthroplasty is a common treatment of osteoarthritis, although unicompartmental knee arthroplasties are frequently used to retain unaffected compartments. Joint space width (JSW) is a major factor in determining treatment. We examined the relationship between JSW and cartilage quality in 60 patients undergoing total knee arthroplasty to assess its accuracy in representing cartilage degradation. Radiographic JSW was recorded, whereas the unaffected compartment of each tibial plateau was examined postoperatively using Collins, Mankin, and Kellgren and Lawrence scores. No correlation was seen between visual or histologic grading and JSW. Histology more accurately represented cartilage quality, yet it is impractical to obtain preoperatively; thus, JSW is the main mode of assessment. However, using JSW solely to indicate unicompartmental knee arthroplasty may overlook disease in apparently unaffected compartments.     

Contributions to hepatic fibrosis in HIV-HCV coinfected and HCV monoinfected patients

OBJECTIVES: The aim of this study was to further explore the severity of liver disease and its predictors in a cohort of hepatitis C virus (HCV) infected patients, some of whom were coinfected with the human immunodeficiency virus (HIV). METHODS: This is a retrospective, cross-sectional study of patients undergoing liver biopsy to stage HCV disease prior to consideration of anti-HCV therapy. RESULTS: A total of 92 HIV-HCV coinfected and 372 HCV monoinfected patients were included. As might be expected, coinfected patients differed from monoinfected patients in a number of ways, including having lower body mass index (BMI), and lower alcohol intake. Liver disease was very similar between the two groups, with mean fibrosis score of 1.45 u for coinfected and 1.53 u for monoinfected (p = NS). Histological inflammation score dominated multivariate models of fibrosis when it was included in them. When only clinical predictors were used in multivariate models, BMI and type 2 diabetes had independent associations in monoinfected patients, whereas low CD4 count, current or nadir, was the only variable with an independent association in coinfected patients. CONCLUSIONS: Coinfected patients do not have uniformly worse liver disease than monoinfected patients. Immune compromise plays an important role in liver disease in coinfected patients, and the role of other clinical factors in liver disease may differ between these two groups, as well.     

Risk factors for initial surgery in pediatric patients with Crohn's disease

BACKGROUND & AIMS: The cumulative incidence of surgery ranges from 40%-70% at 10 years from the time of diagnosis of Crohn's disease in adults. We retrospectively determined the cumulative incidence of and risk factors for surgery (intestinal resection) in pediatric patients with Crohn's disease. METHODS: Uniform data from 989 consecutive Crohn's disease patients (age 0-17 years at diagnosis), collected from 6 different pediatric centers between January 2000 and November 2003 and stored in the Pediatric IBD Consortium Registry, were analyzed. RESULTS: Median follow-up time was 2.8 years (range, 1 day to 16.7 years). One hundred twenty-eight patients underwent surgery. Kaplan-Meier survival estimates of the cumulative incidence of surgery were 17% at 5 years and 28% at 10 years from the diagnosis of inflammatory bowel disease. Univariate Cox proportional hazards models showed leukocytosis (2.85 [hazard ratio]; P = .02), hypoalbuminemia (3.41; P = .05), and anti-Saccharomyces cerevisiae antibody (ASCA) positivity (3.43; P = .05) were associated with increased risk for surgery. Multivariate Cox models showed female gender (1.49; P = .03), initial diagnosis of ulcerative colitis (3.63; P < .0001), poor growth at presentation (2.16; P = .007), and abscess (1.90; P = .009), fistula (2.30; P = .0005), or stricture (3.41; P < .0001) development were associated with increased risk for surgery. Age 3-5 years (0.26; P = .01) or 6-12 years (0.62; P = .01) at diagnosis, fever at presentation (0.50; P = .03), and treatment with infliximab (0.36; P = .0005) or 5-aminosalicylic acid (0.44; P < .0001) were associated with decreased risk for surgery. CONCLUSIONS: Risk stratification during the course of Crohn's disease in pediatric patients will help to guide therapy that may improve the natural history of disease and decrease the need for surgery.     

Peer Reviewed: Racial Disparities in Blood Pressure Control and Treatment Differences in a Medicaid Population, North Carolina, 2005-2006

Introduction

Racial disparities in prevalence and control of high blood pressure are well-documented. We studied blood pressure control and interventions received during the course of a year in a sample of black and white Medicaid recipients with high blood pressure and examined patient, provider, and treatment characteristics as potential explanatory factors for racial disparities in blood pressure control.

Methods

We retrospectively reviewed the charts of 2,078 black and 1,436 white North Carolina Medicaid recipients who had high blood pressure managed in primary care practices from July 2005 through June 2006. Documented provider responses to high blood pressure during office visits during the prior year were reviewed.

Results

Blacks were less likely than whites to have blood pressure at goal (43.6% compared with 50.9%, P = .001). Blacks above goal were more likely than whites above goal to have been prescribed 4 or more antihypertensive drug classes (24.7% compared with 13.4%, P < .001); to have had medication adjusted during the prior year (46.7% compared with 40.4%, P = .02); and to have a documented provider response to high blood pressure during office visits (35.7% compared with 30.0% of visits, P = .02). Many blacks (28.0%) and whites (34.3%) with blood pressure above goal had fewer than 2 antihypertensive drug classes prescribed.

Conclusion

In this population with Medicaid coverage and access to primary care, blacks were less likely than whites to have their blood pressure controlled. Blacks received more frequent intervention and had greater use of combination antihypertensive therapy. Care patterns observed in the usual management of high blood pressure were not sufficient to achieve treatment goals or eliminate disparities.     

Immune Response to Persistent Staphyloccocus Aureus Periprosthetic Joint Infection in a Mouse Tibial Implant Model

Staphyloccocus aureus is one of the major pathogens in orthopedic periprosthetic joint infection (PJI), a devastating complication of total joint arthroplasty that often results in chronic and persistent infections that are refractory to antibiotics and require surgical interventions. Biofilm formation has been extensively investigated as a reason for persistent infection. The cellular composition, activation status, cytokine profile, and role of the immune response during persistent S. aureus PJI are incompletely understood. In this study, we used histology, multiparametric flow cytometry, and gene expression analysis to characterize the immune response in a clinically relevant orthopedic PJI model. We tested the hypothesis that persistent S. aureus infection induces feedback mechanisms that suppress immune cell activation, thereby affecting the course of infection. Surprisingly, persistent infection was characterized by strikingly high cytokine gene expression indicative of robust activation of multiple components of innate and adaptive immunity, along with ongoing severe neutrophil-dominated inflammation, in infected joint and bone tissues. Activation and expansion of draining lymph nodes and a bone marrow stress granulopoiesis reaction were also maintained during late phase infection. In parallel, feedback mechanisms involving T-cell inhibitory receptors and exhaustion markers, suppressive cytokines, and regulatory T cells were activated and associated with decreased T-cell proliferation and tissue infiltration during the persistent phase of infection. These results identify the cellular and molecular components of the mouse immune response to persistent S. aureus PJI and indicate that neutrophil infiltration, inflammatory cytokine responses, and ongoing lymph node and bone marrow reactions are insufficient to clear infection and that immune effector mechanisms are suppressed by feedback inhibitory pathways. These immune-suppressive mechanisms are associated with diminished T-cell proliferation and tissue infiltration and can be targeted as part of adjuvant immunotherapeutic strategies in combination with debridement of biofilm, antibiotics, and other therapeutic modalities to promote eradication of infection. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Association of chromosome arm 9p abnormalities with adverse risk in childhood acute lymphoblastic leukemia: A report from the Children's Cancer Group.

Cytogenetic abnormalities of chromosome arm 9p occur frequently in children with acute lymphoblastic leukemia (ALL). We analyzed 201 such cases (11%) in 1,839 children with newly diagnosed ALL treated between 1989 and 1995 on risk-adjusted protocols of the Children's Cancer Group (CCG). The majority of patients (131; 65%) with a 9p abnormality were classified as higher risk. Nearly all patients had complex karyotypes; most cases had deletions of 9p, add/der(9p), a dicentric involving chromosome arm 9p, and/or balanced translocations and inversions involving 9p. Event-free survival (EFS) estimates at 6 years for patients with and without a 9p aberration were 61% (standard deviation [SD] = 5%) and 76% (SD = 2%; P <.0001). In addition, patients with a 9p abnormality had an increased cumulative incidence of both marrow (P =.04) and central nervous system (P =.0001) relapses. Overall survival also was significantly worse for patients with an abnormal 9p (P <.0001). These effects were most pronounced in standard-risk patients (age 1 to 9 years with white blood cell count <50,000/microL): 6-year EFS of 61% (SD = 9%) versus 80% (SD = 2%; P <.0001). Also, a 9p aberration was an adverse risk factor for B-lineage, but not T-lineage patients. The effect of 9p status on EFS was attenuated, but maintained in a multivariate analysis of EFS after adjustment for Philadelphia chromosome status, age, white blood cell (WBC) count, sex, race, and ploidy group (P =.01). Thus, abnormalities of chromosome arm 9p identify a subgroup of standard-risk patients with increased risk of treatment failure.