Curability and transferability of atopy with allogeneic hematopoietic cell transplantation.

Atopy is excessive production of IgE in response to allergens. We evaluated in patients undergoing allogeneic hematopoietic cell transplantation (HCT) the following hypotheses: (1) Atopy is "curable" in atopic patients receiving HCT from a nonatopic donor (D-R+), and (2) Atopy is transferable from atopic donors to nonatopic recipients (D+R-). Atopic patients with atopic donors (D+R+) and non-atopic patients with non-atopic donors (D-R-) served as controls. We measured levels of multiallergen-specific IgE (A-IgE, atopy defined as ≥0.35 kUA/L) in sera from 54 patients and their donors pre HCT and from the patients at ≥2 years post HCT. Only 7/12 (58%) D- R+ patients became nonatopic after HCT. Only 1/11 (9%) D+R- patients became atopic. Eleven of 13 (85%) D-R- patients remained nonatopic. Unexpectedly, 11/18 (61%) D+R+ patients became nonatopic. In conclusion, contrary to our hypothesis and previous reports, the "cure" of atopy may occur in only some D-R+ patients and the transfer of atopy may occur rarely. The "cure" may not be necessarily due to the exchange of atopic for nonatopic immune system, as the "cure" may also occur in D+R+ patients.

More acute lymphoid leukemia than acute myeloid leukemia blasts are killed by rabbit antithymocyte globulin.

Rabbit antithymocyte globulin (ATG, thymoglobulin), a polyclonal antibody, is used to prevent graft-versus-host disease (GVHD) and graft failure in the setting of allogeneic hematopoietic cell transplantation (HCT). Recent in vitro studies suggest that ATG also has anti-leukemic activity. Whether acute lymphoid leukemia (ALL) or acute myeloid leukemia (AML) is more sensitive to ATG is not known. We used primary cells from 12 B-ALL and 38 AML patients and measured ATG-induced complement-dependent cytotoxicity (CDC) and complement-independent cytotoxicity (CIC) at clinically relevant ATG concentrations (10 and 50 mg/L). At 50 mg/L, ALL blasts were killed to a greater degree than AML blasts by CDC (median 96% vs 50% dead cells, P = 0.001) as well as CIC (median 23% vs 11% apoptotic cells, P = 0.049). At 10 mg/L, the difference was significant for CDC but not CIC. In conclusion, the anti-leukemic activity of ATG, particularly CDC, is more potent for ALL than AML in vitro. If this applies in vivo, ATG-based GVHD prophylaxis may be particularly advantageous for ALL.

Anti-thymocyte globulin's activity against acute myeloid leukemia stem cells.

Rabbit anti-thymocyte globulin (ATG (Thymoglobulin)) kills T cells in vitro and probably also in vivo as it prevents graft-vs-host disease (GvHD) in patients. Recently we demonstrated that ATG at a clinically relevant concentration (10-50 mg/L) kills in vitro not only T cells but also leukemic blasts. In the present study, we investigated whether ATG kills not only leukemic blasts but also leukemic stem cells (LSCs). We used a flow cytometric assay of complement-mediated cytotoxicity (CDC). ATG-induced death of acute myeloid leukemia (AML) cells from patients newly diagnosed with AML was measured among blasts as well as LSCs. At 10 mg/L ATG, blasts but not LSCs were killed. At 50 mg/L ATG, both blasts and LSCs were killed. We also measured ATG-mediated killing of healthy individuals' hematopoietic stem cells (HSCs). Median 2% HSCs from blood and 15% HSCs from filgrastim-mobilized grafts were killed with 50 mg/L ATG, compared to 30% LSCs from the blood of AML patients (p = 0.001 and 0.022, respectively). In conclusion, LSCs are sensitive to ATG, however, only at a relatively high ATG concentration. At that concentration, LSCs are killed to a higher degree than HSCs.

Influence of Chemotherapy on Allergen-Specific IgE.

BACKGROUND: Atopy is defined as excess allergen-specific IgE (A-IgE). IgE is produced by plasma cells that differentiate from allergen-specific B cells. B cells are known to be killed by chemotherapy; however, it is not known whether A-IgE-secreting plasma cells are killed or inhibited by chemotherapy. If yes, serum A-IgE levels would be expected to decrease after chemotherapy. OBJECTIVES: We aimed to determine whether A-IgE levels in atopic individuals (serum A-IgE ≥0.35 kUA/L) decrease into the nonatopic range (< 0.35 kUA/L) after chemotherapy. METHODS: In 105 patients undergoing chemotherapy for acute leukemia, we measured serum A-IgE before and after chemotherapy. In a subset of these patients, we also measured B cell counts before and after chemotherapy. RESULTS: Of the 105 patients, 36 were atopic. In these patients, median A-IgE level before chemotherapy was 1.6 kUA/L whereas the median level after chemotherapy was 0.6 kUA/L (p < 0.001). In 12/36 (33%) patients, A-IgE levels decreased into the nonatopic range. In nonatopic patients (n = 69), the median A-IgE level also dropped: from 0.04 kUA/L before to 0.03 kUA/L after chemotherapy (p = 0.001). Among the total patients (n = 105), the median pre:post-chemotherapy A-IgE ratio was 1.8 (2.6 in atopic and 1.5 in nonatopic patients). In contrast, the median ratio of pre:post-chemotherapy B cell counts was 87.6. CONCLUSIONS: A-IgE levels decrease after chemotherapy but markedly less than B cell counts. Thus, at least some A-IgE plasma cells appear to survive chemotherapy.

Bone in The Endometrium: A Review.

To provide a comprehensive review of the published literature of patients with endo- metrial bone or osseous fragments with a view to critically examine the antecedent clinical presentation, investigations and prognosis after treatment. This systematic review of the literature includes full text articles of published case re- ports and cases series from the following computerized databases: PubMed, Ovid, and Medline between 1928 and 2013. We reviewed a total of 293 patients in 155 case reports and case series. The mean ± SD age at presentation was 32.7 ± 8.9. Approximately 88% of patients had at least one prior surgical uterine evacuation relating to pregnancy termina- tion or loss at a median gestational age of 14 weeks (range of 4-41 weeks). The most common presenting symptom was infertility (56.2%). One hundred twenty- four (66.0%) of the 188 patients attempting pregnancy after treatment achieved pregnancy prior to article publication and the majority (82.3%) were spontane- ous. Spontaneous miscarriage rate remains high (43%); however, most pregnancies ended in live-birth (55%). Bone fragments in the endometrium are most commonly found after pregnancy termina- tion, present with infertility and/or irregular menses, and upon removal, patients rapidly conceive spontaneously.

Antithymocyte Globulin at Clinically Relevant Concentrations Kills Leukemic Blasts.

In contrast to cyclosporine or methotrexate, rabbit antithymocyte globulin (ATG) used for graft-versus-host disease (GVHD) prophylaxis with myeloablative conditioning does not increase the risk of relapse after hematopoietic cell transplantation. The reason for this is unknown. We hypothesized that ATG at concentrations achieved with our standard ATG dose of 4.5 mg/kg exerts antileukemic activity. We measured ATG-induced killing of leukemic blasts via complement-dependent cytotoxicity (CDC) and via complement-independent cytotoxicity (CIC) in marrow or blood from 36 patients with newly diagnosed acute leukemia. The median percentage of blasts killed by CDC was 0.3% at 1 mg/L ATG, 2.8% at 10 mg/L ATG, 12.6% at 25 mg/L ATG, and 42.2% at 50 mg/L ATG. The median percentage of blasts killed by CIC after a 4-hour incubation with ATG was 1.9% at 1 mg/L ATG, 7.15% at 10 mg/L ATG, 12.1% at 25 mg/L ATG, and 13.9% at 50 mg/L ATG. CIC appeared to represent a direct induction of apoptosis by ATG. There was a high variability in the sensitivity of the blasts to ATG; at 50 mg/L, the percentage of blasts killed ranged from 2.6% to 97.2% via CDC and from 1.4% to 69.9% via CIC. In conclusion, ATG at clinically relevant concentrations kills leukemic blasts in vitro. Some acute leukemias are highly sensitive to ATG, whereas others are relatively resistant. This finding could lead to personalized administration of ATG.

The health disparities of uterine fibroid tumors for African American women: a public health issue.

Uterine fibroid tumors (leiomyomas) are the most common benign pelvic tumors in women and are the major indication for hysterectomy. Fibroid tumors are more common and more severe among African American women. Although this disease disproportionately affects the African American population, we understand little about what causes the disparity. Fibroid tumors should be considered a public health issue, given the magnitude of the problem and the costs of health care for this disease. In this review, we examine the burden of disease from fibroid tumors in the African American population and review the natural history, diagnosis, and treatment of uterine fibroid tumors, with emphasis on how these can differ, depending on race. We also focus on the socioeconomic burden caused by the disease and describe the anticipated influence of new health care reforms and funding mechanisms for fibroid tumor research.

The role of Violence Against Women Act in addressing intimate partner violence: a public health issue.

Intimate partner violence (IPV) is defined as violence committed by a current or former boyfriend or girlfriend, spouse or ex-spouse. Each year, 1.3 to 5.3 million women in the United States experience IPV. The large number of individuals affected, the enormous healthcare costs, and the need for a multidisciplinary approach make IPV an important healthcare issue. The Violence Against Women Act (VAWA) addresses domestic violence, dating violence, sexual assault, and stalking. It emphasizes development of coordinated community care among law enforcement, prosecutors, victim services, and attorneys. VAWA was not reauthorized in 2012 because it lacked bipartisan support. VAWA 2013 contains much needed new provisions for Native Americans; lesbian, gay, bisexual, transgender, gay, and queer (LGBTQ) individuals; and victims of human trafficking but does not address the large amount of intimate partner violence in America's immigrant population. There are important remaining issues regarding intimate partner violence that need to be addressed by future legislation. This review examines the role of legislation and addresses proposals for helping victims of IPV.

Impact of anterior scalene lidocaine blocks on predicting surgical success in older patients with neurogenic thoracic outlet syndrome.

OBJECTIVE: Surgical management of neurogenic thoracic outlet syndrome (NTOS) is controversial due to the lack of predictors of success and difficulties in patient selection. We sought to examine the effects of patient demographics, etiology, duration of symptoms, and the selective use of lidocaine and botulinum toxin anterior scalene blocks on outcomes of patients undergoing transaxillary decompression with first rib resection and scalenotomy for NTOS. METHODS: Patients with NTOS who had failed physical therapy and had transaxillary decompression between 2003 and 2009 were reviewed retrospectively from a prospectively maintained database. Patients were stratified to age groups < 40 and ≥ 40 years old. Bivariate and multivariate statistical models of analysis were used. RESULTS: One hundred fifty-nine procedures (16 patients bilateral; three patients with cervical ribs; 84.3% women; median age, 37 years; range, 21-64 years) were identified. Ninety-six patients were < 40 and 63 were ≥ 40 years old. Etiology was similar in both groups: trauma 43% vs 46% and chronic repetitive motion 57% vs 54%. Duration of symptoms was less in the <40 group (38.4 vs 66 months; P < .05). More patients in the ≥ 40 group had other spine, shoulder, or arm operations (38% vs 18%; P < .05). Median follow-up for the cohort was 12 months. Transaxillary decompression was more likely to relieve symptoms in patients <40 vs ≥ 40 years old (90% vs 78%; P < .05). Lidocaine blocks were positive in 89% (49 of 55 patients) in the <40 group and 93% (43 of 46 patients) in the ≥ 40 group. After adjusting for patient presenting factors in multivariate analysis, the impact of a successful lidocaine block in patients ≥ 40 years old was greater than in patients < 40 years old (improvement of surgical success of 14% in the > 40 group vs 7% in the < 40 group; P = .05). Botulinum toxin blocks were successful in less patients, 38% (eight of 21 patients) in the < 40 group and 52% (12 of 23 patients) in the ≥ 40 group but were not predictive of symptom relief after transaxillary decompression. CONCLUSIONS: Although patients with NTOS < 40 years old achieve more symptom relief overall after transaxillary decompression as compared to patients ≥ 40 years old, the selective use of lidocaine blocks is more beneficial in predicting surgical success in patients ≥ 40 years old given that younger patients < 40 years old seem to do well regardless.

Lung transplantation in older patients with cystic fibrosis: analysis of UNOS data.

BACKGROUND: The lifespan for patients with cystic fibrosis (CF) is increasing. As a result, greater numbers of older CF patients are presenting for lung transplantation (LTx). The UNOS database provides an opportunity to examine outcomes for this population. METHODS: We retrospectively reviewed UNOS data to identify 1,637 first-time LTx recipients with the indication of CF between 1999 and 2007. Patients were stratified by quartile age. Our primary end-point was all-cause mortality. Post-transplant survival was compared using Cox proportional hazards regression. RESULTS: Of the patients who met the inclusion criteria, the distribution by age quartile was as follows: Quartile 1 (Q1), age 7 to 20 years, N = 408; Q2, 21 to 27, N = 470; Q3, 28 to 34, N = 365; and Q4, >or=35, N = 394. Patients in the lowest quartile had the lowest 5-year cumulative survival (43%); 19% lower than for patients in Quartile 4 (age >or=35, cumulative survival = 62%; p < 0.001). On multivariable analysis, patients in Q3 and Q4 had a 38% and 32% reduction in cumulative hazard for death, respectively (reference Q1, age 7 to 20) (hazards ratios: Q3, 0.62 [0.46 to 0.85], p < 0.001; Q4, 0.68 [0.5 to 0.93], p = 0.02). Thirty-day and 1-year cumulative survival were not different among the four quartiles (30-day survival: Q1, 96.4%; Q2, 96.2%; Q3, 96.2%; and Q4, 95.5% [p = 0.94]; 1-year survival: Q1, 83.7%; Q2, 83.1%; Q3, 85.4%; and Q4, 83.4% [p 0.88]). Increasing age was associated with decreases in early post-operative infections, reduction in the cumulative hazard of developing bronchiolitis obliterans (BO) syndrome, and decreases in hospitalizations and treatment for rejection. CONCLUSIONS: The UNOS database has provided a large series examining survival after LTx in older CF patients. LTx is safe in this group and older age may be protective against infection, rejection and BO syndrome.