bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Abnormalities of Patient-Reported Outcomes after Recovery from Thrombotic Thrombocytopenic Purpura (TTP) Using Health Related Quality-of-Life (QOL) Measurements.
Authors: Lewis Qurana , Terrell Deirdra R. , Vesely Sara K. , George James N. 
Published: April 2020

Abstract
Patients who survive an acute episode of TTP are expected to have complete recovery. The only currently appreciated risk is the possibility of a recurrent acute episode. However, survivors often describe problems that interfere with daily activities such as decreased energy and poor concentration and memory in spite of normal physical examination and laboratory data. The Oklahoma TTP-HUS Registry has complete follow up data on 333 of 335 consecutive patients with clinically diagnosed TTP or HUS in central-western Oklahoma from January 1, 1989 through December 2005. Since February 1998 we have collected QOL data annually, beginning one year after the initial episode, using the Medical Outcomes Study Short Form-36 (SF-36) to assess eight domains of physical and mental health. We compared our patients to US population norms that have been determined from the total, non-institutionalized US population. Results are reported as the percent of our patients who were within the top 75 percent of the US population values. The parameter of the top 75 percent of the US population was selected to approximate a range of normal function.
Percent of TTP patients in the top 75% of the US Population for all SF-36 domains Data for all TTP patients who had their first QOL less than two years from the time of their initial episode and who did not relapse in that interval SF-36 Domain TTP Patients (n=76) P Vitality 43% &lt;0.01 Role physical 46% &lt;0.01 Physical functioning 44% &lt;0.01 Bodily pain 63% 0.17 General health 33% &lt;0.01 Social functioning 55% &lt;0.01 Role Emotional 62% 0.01 Mental health 61% 0.05 Percent of TTP patients, by clinical category, in the top 75% of the US population for the SF-36 general health domain1 1Data for the general health domain, to compare patients designated in different clinical categories of TTP (n=122) 2Patients with ADAMTS13 deficiency are reported separately, not with their clinical category: 16 were idiopathic, 2 were pregnant, 1 had bloody diarrhea Clinical Category N TTP Patients (n=122) P Idiopathic 57 40% &lt;0.01 Quinine-induced 15 33% &lt;0.01 Preganancy-associated 18 44% &lt;0.01 Bloody diarrhea prodrome 13 38% &lt;0.01 ADAMTS13 &lt;10%2 19 32% &lt;0.01
Patients who have recovered from TTP performed significantly worse than the US population for all domains of the SF-36 except for bodily pain. For the general health domain, patients in all categories were significantly worse than the US population. Thirty-two patients had ≥ 4 QOLs: there was a significant trend for improvement across time in the role physical domain (p&lt;.01); the other 7 domains had no significant trend across time.
CONCLUSIONS: Following an acute episode of TTP, the QOL of patients is worse than the US population, suggesting that the ischemia of TTP may cause persistent physical and cognitive abnormalities.
Deep Venous Thromboses Associated with Peripherally Inserted Central Catheters in Patients with Hematological Malignancies.
Authors: Tran Ha , Chamsuddin Abbas , Winton Elliott F. , Heffner Leonard , Langston Amelia , Waller Ned , Arellano Martha , Khoury H. Jean 
Published: April 2020

Abstract
Deep venous thromboses (DVTs) complicating peripherally inserted central catheters (PICCs) placed for antibiotic administration were observed in 1.4% of patients in the largest study to date that included more than 2000 patients (Clinical Infectious Diseases, 34:1179–1183). The incidence of DVTs associated with PICCs in patients with hematological malignancies is unknown. We designed this retrospective analysis to better determine the incidence, characteristics, and outcomes of PICC-related DVTs on a Leukemia Unit at a large academic institution. Between April 2001 and February 2006, a total of 899 PICCs were placed in 568 patients with hematological malignancies. Ultrasound documented deep venous thromboses occurred in 38 patients (6.69%), a median of 26 days (2–172) after PICC placement. Patient’s characteristics were as follows: median age at the time of PICC insertion 45.5 yrs; 61% male; 37% black and 58% white. At the time of PICC placement 22 (58%) patients had newly diagnosed AML (46%), ALL (36%), lymphoma (13%), or CML (5%). Median platelet count at the time of DVT diagnosis was 106 ×10E3/μL. DVT management included removal of the PICC (71%), thrombectomies/thrombolysis/PTCA (13%), and anticoagulation with heparin (76%), or warfarin (24%). Anticoagulation was subsequently intermittently discontinued due to chemotherapy-induced thrombocytopenias. With a median follow up of 601 days, there were no documented pulmonary emboli or hemorrhages; 50% were in remission, 8% had relapsed disease, and 39% were deceased. In summary, patients with hematological malignancies appear to have a higher incidence of PICC-associated DVTs compared to patients without malignant hematological disorders with PICCs inserted for antibiotic administration. Risk factor analysis is in progress.
Inhibition of Signal Transducer and Activator of Transcription 6 Activity in the Hodgkin Lymphoma Cell Line L1236 Induces Growth Inhibition and Apoptosis.
Authors: Liu Cheng , Andersson Margareta , Xu Dawei , Claesson Hans-Erik , Bjorkholm Magnus , Sjoberg Jan 
Published: April 2020

Abstract
Signal transducer and activator of transcription 6 (STAT6) plays a central role in interleukin (IL)-4 and -13 signaling. Upon binding of the cognate receptors by these cytokines, STAT6 becomes phosphorylated by Jak family kinases and subsequently translocates to the nucleus where transcription of its target genes is regulated. Expression of IL-13 and its receptor are common features of Hodgkin lymphoma (HL) tumor cells, the so-called Hodgkin Reed-Sternberg (H-RS) cells, in which this cytokine has been shown to act as an autocrine growth factor. Consequently, constitutively phosphorylated STAT6 with a nuclear localization is a common and distinctive feature of H-RS cells in classical HL. We knocked down STAT6 expression in the HL cell line L1236 with small interfering RNA (siRNA) and found that inhibition of STAT6 activity results in cell growth inhibition, decreased viability and increased apoptosis. The results depict a central role of STAT6 in the growth of H-RS cells and indicate that STAT6 could be a potential target for therapeutic intervention in HL. Moreover, in order to identify the target genes of this transcription factor in H-RS cells, a combined approach of RNA interference and microarray is performed and the results will be presented.
Female Gonadal Toxicities after Treatment of Primary Hodgkin Lymphoma (HL). Analysis of the LENT-SOMA Questionnaire Registered in the Database of the German Hodgkin Study Group (GHSG).
Authors: Behringer Karolin , Gilman Elena , Borchmann Peter , Heuser Eva , Pfistner Beate , Diehl Volker , Engert Andreas 
Published: April 2020

Abstract
Introduction:
As a consequence of the impressive long-term remission rates in Hodgkin Lymphoma (HL), the reduction of treatment-related complications is becoming increasingly important. The most important treatment-related toxicities are secondary malignancies, infertility, pulmonary, cardiac, and thyroid dysfunction. Here, we report results of the prospectively planned LENT-SOMA questionnaire to determine female gonadal toxicities in women successfully treated for HL.
Patients and methods:
Between 1998 and 2002, the GHSG has conducted the fourth generation of clinical trials for the treatment of early, intermediate and advanced stage HL (HD 10–12) involving a total of approximately 4000 evaluable patients. The LENT-SOMA questionnaire was sent out to the participating centers 2, 5 and 10 years after a patient’s randomisation to evaluate cardiac, pulmonary, and gonadal dysfunction after HL treatment. To focus on female gonadal toxicities, questions referred to the menstrual cycle, infertility, and osteoporosis.
Results:
Overall, approximately 1.900 (50%) LENT-SOMA questionnaire after 2 years were identified. A total of 568 questionnaire were evaluable for the question of menstrual cycle after therapy. Amenorrhea was most frequent in women with advanced stage after treatment with 8 cycles of escalated BEACOPP compared to treatment consisting of 4 cycles of escalated BEACOPP plus 4 cycles of BEACOPP baseline (45% vs. 19%, p&lt;0.0001). A regular cycle was most commonly reported in women treated with two or four cycles of ABVD (98.8% and 95.9%). The frequency of gonadal dysfunction will be evaluated according to treatment modality (chemotherapy, chemo- and radiotherapy) and it will be analysed with respect to age.
Conclusion:
Female gonadal toxicities after HL treatment include amenorrhea, infertility and osteoporosis. The first analysis of the LENT-SOMA questionnaire focussing on female gonadal dysfunction will be presented.
High Grade Transformation in Splenic Marginal Zone Lymphoma: A Description of a Series of 8 Cases.
Authors: Dungarwalla Moez R. , Wotherspoon Andrew , Morgan Gareth , Catovsky Daniel , Dearden Claire E. , Matutes Estella 
Published: April 2020

Abstract
Splenic marginal zone lymphoma (SMZL) without or with villous lymphocytes (SLVL) is a low grade B cell non-Hodgkin’s lymphoma that comprises &lt;1% of lymphoid malignancies. SLVL is indistinguishable histologically from SMZL and it is believed that the 2 entities represent different phases of the same process in the spleen and the bone marrow. Characteristic features of SMZL are splenomegaly, moderate lymphocytosis, immunophenotype with a CLL score &lt; 2 and nodular/intrasinusoidal pattern of bone marrow infiltration. Despite its slow clinical course, and response to splenectomy, approximately 50% of deaths in patients with SMZL are caused by progressive disease. As in other low grade lymphoproliferative disorders, SMZL may undergo high grade transformation. We describe 8 cases of SMZL that showed clinical, morphological and histological features of progression to large B cell lymphoma. These 8 cases represent 19% of our series of 41 SMZL patients followed up between 1996 and 2006. Patients were aged between 44 and 76 years, and there were 4 men and 4 women. Progression to high grade B cell lymphoma occurred between 1 and 48 months from diagnosis. The cases can be divided into 2 distinct groups on the basis of the site of transformation. Those cases with high grade transformation in the bone marrow had a median overall survival of 10 months, although 1 patient did attain a complete remission with combination chemotherapy (R-CHOP) and is alive at 12 months. In contrast, there were 3 cases of transformation in peripheral lymph nodes with a median overall survival of 60 months. Large B cell lymphoma was also diagnosed in the spleen in the initial stages of the disease in 1 case. This patient achieved a complete remission with R-CHOP post splenectomy, and is still alive at 36 months follow up. In a previous report of transformation to large B cell lymphoma in SMZL (Camacho et al, Am J Surg Pathol 2001) a 13% incidence was reported. In our series of 8 cases the incidence of transformation is 19%. Hence it appears that while the incidence of large B cell transformation seems to be higher than in CLL (1–10%) it is lower than that reported in follicular lymphoma (25–60%). Two of the 4 cases of high grade transformation in the bone marrow had previously been treated with fludarabine in the year prior to their progression to large B cell lymphoma. In 1 of these cases Epstein Barr Virus encoded RNA was detected in the malignant cells at the time of transformation. This may suggest that EBV is involved in the pathology of SMZL transformation, and treatment with immunosuppressive agents such as the purine analogues, may increase this risk. In our series of 41 patients, 6 have received fludarabine therapy and the risk of high grade transformation in this small group is significantly higher at 33% (2/6).
The Prevalence of Second Malignancies and Autoimmune Diseases in Patients with Lymphoproliferative Disorders.
Authors: Seery Tara E. , Sycheva Tatyana , Oo Thein H. 
Published: April 2020

Abstract
BACKGROUND: The incidence and prevalence of second malignancies and autoimmune diseases are high in patients with lymphoproliferative disorders (LPD). However, there is lack of specific data and the relative risks compared to general population are unknown.
METHODS: We performed retrospective chart analysis of 185 patients with LPD in a tertiary hospital from 2000 to 2006. The data was based on available chart reviews and interdepartmental charge codes. All second malignancies and autoimmune diseases were documented irrespective of time of onset.
FINDINGS: M:F ratio = 1.1: 1.0 (97M, 88F). Median age 56. Cases consisted of: CLL/SLL 52(28.1%), multiple myeloma 28(15.135%), unspecified Non-Hodgkin’s Lymphoma 40(21.62%), large cell 24(12.97%), follicular 16(8.64%), marginal zone 11(5.94%), mantle 4(2.16%), T-cell 1(0.54%), and Hodgkin’s 9(4.86%). 37 second malignancies were documented. The prevalence was as follows: prostate 14(7.56%), breast 7(3.783%), kidney 3(1.621%), skin 3(1.621%), colon 2(1.081%), lung 3(1.621%), CMML 1(0.54%), AML 1(0.54%), larynx 1(0.54%), vulva 1(0.54%), pituitary 1(0.54%). The US prevalence of cancers as of January 2003 (population 299,259,581) based on the SEER ( Surveillance, Epidemiology and End Results) data is as follows: all cancers 3.5073%, prostate 0.648%, breast 0.792%, colon 0.357%, kidney 0.077%, lung 0.119%, larynx 0.033%.
Relative risks for second malignancies in LPD patients were calculated (see table). 55 (29.7%) autoimmune diseases were also documented: hypothyroidism 34(18.378%), ITP 10(5.405%), rheumatoid arthritis (RA) 6 (3.243%), hemolytic anemia 3(1.621%), Sjogren’s 1(0.54%), cryoglobulinemia 1(0.54%). The prevalence of autoimmune diseases in the USA is 3.21%. The prevalence of specific autoimmune diseases except RA is unknown in the available literature. The relative risk of autoimmune disorders in LPD patients is 9.25 folds.
DISCUSSION: Our data shows that the prevalence of some second malignancies (renal, prostate, lung, laryngeal, breast, colon) and autoimmune disorders are very high in LPD patients. Due to lack of SEER data, we were unable to calculate the relative risks of other cancers and autoimmune diseases. The relative risk of a second malignancy is increased up to 5-fold (up to 21-fold with renal cancer) and autoimmune diseases up to 9.25-fold. This study has limitations in terms of the sample size and unavailability of some SEER data. However, the results are provoking and need to be validated in larger studies.
Relative Risk of Second Malignancy Cancer Types Lymphoproliferative Disorders n=184 General Population n=299,259,581 Relative Risk All Cancers 20.0% (37) 3.507% 5.702 Prostate Cancer 7.567% (14) 0.648% 11.677 Breast Cancer 3.783% (7) 0.0792% 4.776 Renal Cell Cancer 1.621% (3) 0.077% 21.05 Lung Cancer 1.621% (3) 0.119% 13.621 Colon Cancer 1.081% (2) 0.357% 3.028 Laryngeal Cancer 0.540% (1) 0.033% 16.363
Gender and Regional Differences in In-Hospital Mortality in Patients with Sickle Cell Anemia (SCA) in the United States: Results from the Nationwide Inpatient Sample (NIS) 1993-2003.
Authors: Haywood Carlton , Lanzkron Sophie 
Published: April 2020

Abstract
Background: The purpose of this study was to use the NIS to describe hospital utilization and in-hospital mortality among adults with SCA in the US between 1993-2003.
Methods: The NIS is designed to approximate a 20% stratified sample of U.S. community hospitals. We restricted our analyses to discharge records with ICD-9-CM diagnosis codes 28261 or 28262 (SCA without/with crisis), and where the age was listed as 18 or older. Analyses were conducted using tests of linear combinations of coefficients, χ2, and linear and logistic regression.
Results: There were an estimated 705,080 hospitalizations over the time period (mean of 64,098 hospitalizations/year). 54% of all hospitalizations were for females. 50% of the hospitalizations were expected to be paid for by Medicaid. The mean patient age over the time period was 31.3 yrs. The mean patient age increased from 30.3 in 1993 to 32.1 in 2003 (p &lt; 0.001). Mean age over time increased even after adjusting for the gender makeup and hospital region (β=0.162, p &lt; 0.001). There were no gender differences in the median age (30) of patients. Mean length of stay (LOS) was 6.5 days for the time period. LOS decreased from 7.5 days in 1993 to 6.4 days in 2003 (p=0.001). Adult women experienced longer LOS than adult men (6.8 days vs. 6.3 days, p &lt;0.001). This difference remained significant even after controlling for age, time, insurance status, and hospital region (β = 0.49, p&lt;0.001). Mean charges/discharge increased from $16,799 in 1993 to $22,281 in 2003, even after adjusting for inflation (p &lt; 0.001). There were an estimated 4497 in-hospital deaths during the time period (0.64% of hospitalizations). The median age at death was 38. The median age at death increased from 35 in 1993 to 42 in 2003 (p = 0.0061). This was due to an increase in age of death (39) for women (p=0.0052). In men the median age of death (37) did not change over time(p=0.4352). In bivariate analyses of median age at death, women were older than men (39 vs. 37 p=0.0056). A simple logistic regression of deaths over time found no significant trends in the odds of an in-hospital death over the time period. In a multivariate model of death over time patients in the South and the West experienced higher odds of an in-hospital death than patients in the Northeast and Midwest.
Conclusions: Our analysis shows that women with SCA have longer in-hospital LOS than men, and are older in age at death than men. While the median age at death among persons hospitalized with SCA has been increasing since 1993, this increase is seen exclusively in women. There has been no change in longevity in men hospitalized with SCA over the time period studied.
Human Herpesvirus (HHV) 8 K1 Suppresses Fas-Mediated Apoptosis and Binds to the Fas Complex.
Authors: Maeng Hoyoung , Wang Shu , Wang Suizhao , Young Daniel , Samaniego Felipe 
Published: April 2020

Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV or HHV-8) is associated with multicentric Castleman’s disease, primary effusion lymphoma (PEL), and Kaposi’s sarcoma. Malignant tumors are frequently associated with resistance to Fas-mediated apoptosis, which is a common obstacle to the successful treatment of many different types of cancers. Oncoprotein K1 encoded by HHV-8 is a transmembrane protein with an immunoreceptor tyrosine-based activation motif (ITAM) sequence in its short cytoplasmic domain, which is constitutively phosphorylated (J Natl Cancer Inst Monogr. 28; 15–23, 2001). We have found that K1-expressing cells are resistant to apoptosis and K1 directly binds Fas to inhibit apoptosis. K1-transfected BJAB cells were resistant to Fas-induced apoptosis, but not to other stimuli including tumor necrosis-related apoptosis-inducing ligand or radiation. K1 transgenic mice showed lymph node hyperplasia and large spleens. Nine out of 12 K1 transgenic mice survived injection of 0.3 mg/gram activating anti-Fas (Jo2) antibody whereas 13 out of 22 control mice died with hepatocyte apoptosis (p=0.03). We prepared deletion and point mutants of K1 and Fas to map their respective binding sites.
Immunoprecipitation-immunoblotting analysis of the transfectant cell lysates showed that binding occurred through the extracellular domains of K1 and Fas. Also, we have found that preligand assembly domain-deleted Fas mutants (amino acids 1-66 deleted) still bind to K1. The deletion mutants encompassing cysteine-rich domains 1, 2, and 3 of the extracellular domain of Fas are currently being tested for mediating binding to K1. These results support the presence of an apoptosis regulatory system based on Fas-protein interactions. By characterizing this mechanism, we will lay the foundation of an apoptosis regulatory pathway that may explain apoptosis resistance of many cancers.
Evaluation of Microsatellite Instability in Gastric MALT Lymphomas.
Authors: Siakantaris Marina P. , Angelopoulou Maria K. , Lilakos Konstantinos , Metaxas Yannis , Moschoyianni Maria , Gamaletsou Maria , Vassilakopoulos Theodoros P. , Kyrtsonis Marie-Christine , Korkolopoulou Penelope , Panayiotidis Panayiotis , Pangalis Gerassimos A. 
Published: April 2020

Abstract
BACKGROUND: Microsatellite instability (MSI) is a major mechanism of carcinogenesis in hereditary nonpolyposis colorectal cancer, sporadic colon cancer, as well as other solid tumors. It is also encountered in gastritis and other chronic inflammatory conditions. Gastric MALT lymphomas are associated with chronic antigenic stimulation due to Helicobacter pylori (H.P) infection, leading to chronic gastritis, before converting to overt lymphoma.
AIM: The evaluation of the presence of MSI in gastric MALT lymphoma lesions at diagnosis and during follow-up, after H.P eradication and/or chemotherapy.
METHODS: Genomic DNA was extracted from formalin-fixed paraffin-embedded MALT lymphoma gastric biopsies. Blood genomic DNA was used as control. A pentaplex PCR was performed using primers for 5 different mononucleotide loci (NR21, NR24, NR27, BAT25 and BAT26). Sense oligonucleotides were labeled with WellRead fluorophores and products were run on a CEQ8000 apparatus (Beckman Coulter). Allele scoring was performed using the specific software. For the definition of MSI, 2/5 loci had to show banding shifts or gains outside the quasimonomorphic area for each marker.
RESULTS: 10 MALT lymphoma patients at diagnosis were studied and peaks were compared between stomach and blood samples. All 5 markers studied did not reveal any additional peaks when blood and gastric DNA were compared. In 4 patients follow-up gastric biopsies were available, after H.P eradication, as well as after chemotherapy treatment. There was no evidence of MSI in the serial gastric biopsies of these patients.
CONCLUSIONS: MSI was not detected in any gastric biopsies of this small group of MALT patients, either at diagnosis, or after treatment. The role of MSI in the lymphomagenesis of this distinct type of lymphoma needs to be further evaluated in serial specimens in a larger series of patients.