bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Implications of Anemia in Heart Failure (HF) Patients (pts).
Authors: Puente Dolores , Colorio Cecilia , Ratto Roxana , Descalzo Martin , Rossi Andrea , Perea Francisco , Diez Mirta , Forastiero Ricardo , Tabares Maria , Favaloro Liliana , Pombo Gonzalo , Feldman Leonardo 
Published: April 2020

Abstract
Previous studies have shown that anemia is frequently associated with higher morbidity and mortality in HF pts. Our aim was to determine the impact of anemia in pts hospitalized with congestive HF at our hospital. We analyzed data from 277 pts with diagnosis of HF admitted between 1 June 2004 and 31 December 2005, with a follow up of at least 6 months. Anemia was defined as hemoglobin (Hb) &lt;11,5 g/dl. HF was classified according to Framingham criteria. Previous history of arterial hypertension, diabetes, dislipemia, chronic renal insufficiency and ACE inhibitors treatment was recorded. Ischaemic and non- ischaemic etiology of cardiopathy was established. Renal disfunction was defined as creatinin concentraction &gt;1.9 mg/dl. Pts with HF were assigned to group A (with anemia) or B (control). Statistical analysis was performed using Pearson’s Chi square, Spearman’s rho, Fisher test and Kaplan Meyer survival function.
Results: We evaluated 229 (82,7%) pts with a median follow up of 594 days (range: 1–1129 days). Mean age was 68,02 years (median 71, range: 17–91). 143/229 (62,4%) were male. In 75 /229 (32.75%) cases a Hb &lt; 11,5 g/dl was measured at admission. The mean Hb was 13,1 g/dl for the entire group. Anemia pts showed a mean Hb of 10.6 g/dl. Demographic, clinical and outcome features are shown in table 1.Group A showed a higher number of readmissions because of HF and other cardiac.
Conclussions: In our analysis the prevalence of anemia was 33% in pts hospitalized for HF. There was no significant differences among clinical variables between anemic and non-anemic pts. Anemia was associated with worse clinical outcome (Group A pts required more readmissions for HF and other cardiological causes)and all cause mortality. Mean survival was longer in Group B pts.according to Kaplan Meyer analysis.
TABLE 1: RESULTS GROUP A (n=75) GROUP B (n= 154) p Male 42 (56%) 101 (65.5%) Mean age (years) 70.38 (R:20–90) 67.1 (R:17–91) Mean Hb (g/dl) 10.6 14.3 Ischaemic cardiopathy 38(50,6%) 78(50.6%) Non ischaemic cardiopathy 41(54,6%) 78 Arterial hypertension 54(72%) 106(68.8%) Diabetes 24(32%) 33(21.4%) Dislipaemia 35(46.6%) 64(41.5%) Chronic renal insufficiency 18(24%) 19(12.3%) 0.03 Previous ACE inhibitors treatment 25(33%) 71(46%) 0.08 Acute pulmonary edema 12(16%) 15(9.7%) Creatinin concentration &gt; 1.9 mg/dl 16(21.3%) 18 (11.6%) Hospitalization days (mean) 9.6 (R: 1–51) 8.1(R:1–59) Readmission for HF 37 190 0.001 Readmission for other cardiologic causes 20 109 0.017 Readmission for non cardiologic diseases 18 58 Mean survival (days) 499 (R:1–1091) 658 (r=1–1129) 0.166 Global mortality 25 (33%) 32(21%) 0.05 HF related mortality 13 (20.9%) 24 (14.3%) Figure Figure
L-Glutamine Therapy Improves Minute Ventilation of Sickle Cell Anemia Patients.
Authors: Macan Henry R. , Porszasz Janos , Tsurugaya Hideki , Razon Rafael L. , Koh Han , Casaburi Richard , Tanaka Kouichi R. , Niihara Yutaka 
Published: April 2020

Abstract
We have demonstrated previously that oral L-glutamine administration can improve NAD redox potential in sickle red blood cells (RBC) and decrease the endothelial adhesion rate of sickle RBC. Additionally, preliminary results showed that L-glutamine therapy improved the exercise endurance of sickle cell anemia patients. Following up on this study, minute ventilation and work rate were evaluated. After proper consent, 6 homozygous sickle cell anemia volunteers participated in this two-part study. The first part was incremental work rate testing where the work rate was increased incrementally. The second part was the constant work rate test, in which 80% of the maximum work rate of the incremental test was utilized. Patients were observed for changes in ventilation. These tests were conducted at baseline and after 8 to 12 weeks of therapy with oral L-glutamine at 30 grams a day. There were 6 patients who completed the incremental work rate test and 4 patients who completed the constant work rate test, respectively, at baseline and after treatment. Two of the patients withdrew prior to the completion of the follow-up testing. The results were as follows: On the incremental test, there was an upward trend in peak work rate with an average of 3.5 ± 8.7 watts/min (88.7 ± 25.6 vs. 91.5 ± 21.7; ρ&gt; 0.05). Minute ventilation (VE) showed an average improvement of −4.8 ± 3.9 liters/min (61.2 ± 9.8 vs. 56.4 ± 9.9; ρ value of 0.05). The improved ventilation may be secondary to increased pulmonary blood flow inferring an increased cardiovascular oxygen delivery. On the constant work rate test, there was significant increase in exercise duration with an average of 1.4 ± 0.8 minutes (5.9 ± 1.6 vs. 7.3 ± 1.1; ρ&lt; 0.05). The minute ventilation (VE) showed an average decrease of −11.0 ± 11.6 liters/min (66.5 ± 24.9 vs. 55.5 ± 14.5; ρ&gt; 0.05). This could be indicative of improved oxygen delivery to the exercising musculature despite the absence of a preparatory exercise training program. The data confirm our preliminary report suggesting that L-glutamine therapy improves the exercise endurance of sickle cell anemia patients.
Test Mean + SD ρ value Pre Post Paired Δ (two-tailed t-test) Incremental Work Rate Peak Work Rate (watts/min) 88.7 ± 25.6 91.5 ± 21.7 3.5 ± 8.7 0.37 VE (liters/minute) 61.2 ± 9.8 56.4 ± 9.9 −c4.8 ± 3.9 0.05 Constant Work Rate −Duration (minutes) 5.9 ± 1.6 7.3 ± 1.1 1.4 ± 0.8 0.04 −VE (liters/minute) 66.5 ± 24.9 55.5 ± 14.5 −11.0 ± 11.6 0.15
Pipkiia and Beta-Globin: Transcripts Differentially Expressed in Reticulocytes and Associated with High Levels of Hb H in Two Siblings with Hb H Disease.
Authors: Sonati Maria F. , Wenning Marcia R. , Mello Maricilda P. , Andrade Tiago G. , Lanaro Carolina , Albuquerque Dulcineia M. , Titular Sara Saad , Titular Fernando F. Costa 
Published: April 2020

Abstract
Heterogeneous amounts of Hb H have been detected in peripheral blood of alpha-thalassemic patients even when they carry the same mutation association. This suggests the involvement of other modulating factors besides the thalassemia determinants. To address this issue, we investigated differential gene expression in reticulocytes from two Brazilian siblings of mixed ethnical origin (Chinese and African) in whom Hb H disease is caused by the -a3.7/--SEA genotype. One is a 21-year-old male, and the other a 19-year-old female. Their hemoglobin H levels are 18.7 and 5.0%, respectively. By using the mRNA differential-display reverse-transcription polymerase chain reaction (DDRT-PCR) and suppression subtractive hybridization (SSH) techniques, we identified two main transcripts in both procedures, one corresponding to the phosphatidylinositol-4-phosphate-5-kinase type II-alpha (PIP5KIIA) gene and the other corresponding to the beta-globin gene, both overexpressed in the patient with the higher percentage of Hb H. This result was validated by quantitative RT-PCR using two endogenous genes (GAPDH and BAC). PIP5KIIA expression, in arbitrary units (AU), was 0.108701 in the patient with the higher Hb H, 0.031646 in the other and 0.01561 in the normal control, while beta-globin gene expression was 1.13882, 0.71080 and 0.37631 AU, respectively. Reticulocyte RNA samples obtained from three beta-thalassemia intermedia patients showed a very low level of PIP5KIIA expression. Type II PIP kinases produce phosphatidylinositol 4.5 biphosphate (PI4.5P2) by phosphorylating phosphatidylinositol-5-phosphate. PI4.5P2 is a pleiotropic regulatory molecule involved in diverse cellular activities, including modulation of actin cytoskeleton, protein localization and gene expression. Our results suggest that PIP5KIIA may be one of the factors related to the beta-globin gene expression and to the different levels of Hb H in alpha-thalassemic patients. Its exact mechanism of action, however, remains to be determined.
Neurological Manifestations in Gaucher Disease Patients and Relatives.
Authors: Giraldo Pilar , Alfonso Pilar , Latre Paz , Pocovi Miguel ,   Spanish Group Gaucher Disease
Published: April 2020

Abstract
Aims: Gaucher disease (GD) is characterized by a wide spectrum of manifestations. Several reports have indicated that GD relatives could developed neurological abnormalities. In order to detect neurological symptoms in GD patients and their relatives we have designed a specific prospective inquiry in Spanish GD families.
Patients and Methods: the Spanish GD Registry is an independent registry working since 1993, sponsored by the Spanish Gaucher Foundation (FEETEG). From January to December 2006 we have perform a postal survey contacting 42 physicians and 92 families to evaluate neurological symptoms and correlated with genetic characteristics. The data were included in a SPSS 12.0 data base to perform statistical analysis using descriptive parameters, ANOVA, t-test and correlation study including Pearson coefficient.
Results: We have obtained information from 72 families (78.3% responses) that included 92 type 1 and 7 type 3 GD patients and 266 relatives. Thirty (32.6%) of type 1 GD reported any neurological problem: tremor 8 (8.7%), uncordinated movements 9 (13.8%), concentration defects 11 (11.9%), strabismus 7 (7.6%), deafness 8 (8.7%), Parkinson disease (PD) 7 (7.6%), peripheral neuropathy 10 (10.9%). Thirty six (13.5%) first or second degrees relatives from 72 families presented neurological manifestations: PD 14 (5.3%), epilepsia 8 (3.0%), tremor 7 (2.6%), deafness 2 (0.7%), others 5 (1.9%). Patients with PD had mutations: S364R, D409H, L444P, [IVS2-2A&gt;G]+ [c.(− 203)A&gt;G], c.500insT, L336P. In relatives with PD a wide spectrum of mutations were observed: L444P, N370S, V398I, G202R, c.1439–1445del7, [E326K]+[N188S] and c.953delT, in others neurological manifestations as epilepsia, tremor or peripheral neuropathy predominant mutations were D409H, G195W, R120W; R147X, L336P and G377S.
Conclusions: We have found a higher incidence than expected of PD and other neurological symptoms in GD1 patients and relatives. These manifestations appear frequently in carriers of L444P or rare mutations. It is important to perform a systematic neurological exam in GD1 patients and carriers with risk mutations. This work is partially supported by the grant FIS: 06/1253.
Clinical Significance of Cytocentrifuge Preparation Analysis of Low-Cell-Count Cerebrospinal Fluid Specimens.
Authors: Lajeunesse-Viens Guylaine , Dufault Bernadette , Weng Xiaoduan , Lemieux Bernard , Florescu Marie 
Published: April 2020

Abstract
Introduction: The usefulness of performing a cytocentrifuge preparation (CCP) analysis on cerebrospinal fluid (CSF) containing less than 5 cells has never been studied. To determine if the CCP analysis has a clinical impact on central nervous system (CNS) management of patients with CSF samples containing less than five cells, we correlated the result of CCP to cytomorphology and flow cytometry.
Methods: From November 20th 2005 to July 18th 2007, CCP analysis were performed on 105 CSF consecutive samples containing less than 5 cells from patients with various cancers. For each of these samples, a research via computerized data was conducted to obtain cytomorphology and flow cytometry results. If results were positive or inconclusive, the clinical history and treatment were reviewed.
Results: All 105 samples had negative CCP results. Of the 105 samples, 74 (70,5%) had available cytomorphologies, with 5 (6,8%) being positive, confirming central nervous system infiltration. All 5 patients received treatment for their CNS involvement. The sensitivity of cytomorphology was 83,3%(5/6) and its specificity 100% (68/68).Of the 105 samples, 23 (21,9%) had available flow cytometries: 4 of the 23 (17,4%) cytometries were positive, 2 correlated by positive cytomorphology and treated. 2 had negative cytomorphology with one patient receiving treatment. The sensitivity of cytometry was 75% (3/4) and the specificity 94,7% (19/20).
Conclusion: We found no advantage to performing CCP analysis on CSF samples of less than 5 cells. However, this suggests that performing both cytomorphology and flow cytometry allows a better detection and management of CNS infiltration.
Sequential Serum Cytokine Levels after Autologous, Related and Unrelated Allogeneic Stem Cell Transplantation: Reflection of Immune Reactivity and Reconstitution.
Authors: Fagoaga Omar R. , Nehlsen-Cannarella Sandra L. , Ratanatharatorn Voravit , Martinelli Christine M. , Lum Lawrence G. , Uberti Joseph P. 
Published: April 2020

Abstract
Conditioning regimen in HSCT induces production of inflammatory, regulatory and growth-promoting cytokines. Cytokines are known to mediate alloresponses and heighten GVHD. We prospectively studied sequential cytokine levels in 38 recipients of HSCT (autologous 10, allogeneic related 10 and unrelated 18). Serum TNFα, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IFNγ, G-CSF, GM-CSF, MIP1α, MIP1β levels were measured. Also, Th1 and Th2 cytokines were evaluated as a ratio: Th1/Th2 = IL-2 + IFNγ /IL-4 + IL-10 and Type 1/Type 2 = IL-2 + IFNγ / IL-4 + IL-5 + IL-10. Samples were collected at baseline prior to conditioning regimen and at 4–6 day intervals up to day 95 postHSCT. We report only the significant findings here. In autologous HSCT, IL-5 peaked 192-fold (288.5pg/mL, p=0.0005) at 7d postHSCT over preHSCT levels (1.5pg/mL). At day 15d postHSCT, IL-1α levels decreased 1.9-fold to 0.2 pg/mL under preHSCT levels of 2.3pg/mL and increased 1.9-fold at 40d postHSCT (p=0.0301). In related alloHSCT, the levels of IL-1β increased 3.1-fold to a peak of 16.2 pg/ml at 51d postHSCT (p=0.001) compared to preHSCT level of 5.2pg/mL. IL-2 levels increased 2.2-fold (p=0.001) during the 2nd month postHSCT compared to preHSCT (1.5pg/mL) levels. IL-4 decreased 8.1-fold (p=0.001) at 27d postHSCT compared to preHSCT levels (4.9 pg/mL). IFNγ levels increased 1.5-fold to a plateau after 51d postHSCT compared to preHSCT levels (5.8pg/mL, p=0.017). In unrelated alloHSCT, the levels of TNFα increased 1.7-fold at 60d and 68d postHSCT compared to preHSCT levels of (8.94 pg/mL). IL-10 levels increased 5-fold (p=0.028) to peak at 27d postHSCT compared to preHSCT levels of 2.5pg/mL and to levels after the 1st month postHSCT. The Type1/Type2 ratio decreased 2.5-fold (p=0.023) to a nadir at 27d postHSCT from baseline and returned to preHSCT values by approximately 3 months postHSCT. In unrelated HSCT, Th2 polarization increased in the first month postHSCT due to higher levels of IL-5 and IL-10. After the first month, Th2 dominance subsided, probably due to T-cell recovery and its response to histoincompatibility. The related HSCT showed marked Th1 polarization after the first month of HSCT during which high levels of IL-4 declined and levels of IL-2 and IFNγ increased (Figure 1). Increased IL-5 levels in autologous HSCT is consistent with reconstitution of humoral response in the absence of allostimulation. In summary, we demonstrate some of the dynamic cytokine interactions occurring in the clinical course of recipients undergoing autologous, allogeneic related or unrelated HSCT. The kinetics of Th1 and Th2 levels may reflect the cellular immune reconstitution that could help us design immunotherapeutic interventions.
Figure Figure
ETP in the Discrimination of Liver Disease from DIC.
Authors: Tran Minh H. , Hassett Andrea L. Cortese 
Published: April 2020

Abstract
Introduction Endogenous Thrombin Potential (ETP) is felt to offer a global assessment of coagulation status using continuous photometric measurement of fluorescence emitted, followed by cleavage of a synthetic thrombin substrate. In this study we sought to explore differences in the ETP profile of patients diagnosed with Dissemintated Intravascular Coagulation (DIC) and to examine whether ETP can aid in the discrimination of patients with DIC or End Stage Liver Disease, who can often display similar testing profiles.
Methods Patients with test results interpreted as diagnostic for DIC, Liver Disease (LD), and neither DIC nor Liver Disease (NCD) were selected for evaluation. A total of 55 potential patients were identified and, of these, 45 (82%) were suitable for testing. Samples for testing had been collected in trisodium citrate, double centrifuged, and stored at −70° C for a mean of 15 months. The ETP test (Dade Behring, Marburg, Germany) was performed utilizing the BCS instrument according to the manufacturer’s guidelines. Results for T Lag, T Max, C Max, and AUC were compared between patient groups using two tailed T-test with a P value of &lt;0.05, considered significant.
Results Tests were uninterpretable in 9/45 samples (20%) and therefore the total patient data set included 36 samples (10 in the LD group, 14 in the DIC group, and 12 in the NCD group). There were 7 female and 13 male controls (NC). Liver disease patients express lower values for T Lag and T Max than do DIC patients and lower C Max and AUC than either NCD or NC groups. All ETP variables are significantly lower in the DIC group vs either NCD or NC. NCD and NC groups exhibit minor, but significant differences in all variables, the greatest differences being lower C Max and AUC in NCD vs NC (see Figure 1). Similar differences were observed in gender specific analysis.
Conclusion While ETP determination may be helpful as an additional piece of information in distinguishing between DIC and End Stage Liver Disease patients, differences between the two groups were minor and there was considerable overlap. Paradoxically, the T Max (time to peak thrombin generation) was longer, and both the C Max (which represents the slope of the rise in thrombin generation) and AUC (total thrombin generation) lower, in DIC than in all other groups compared. This is possibly the result of inhibition from significantly higher levels of fibrinogen degradation products and D-Dimers in the DIC vs Liver Disease and non-DIC groups (data not shown). Additional studies using ETP in DIC, Liver Disease, and other hyper- and hypo-coagulable states are necessary.
ETP Variables in Various Patient Groups ETP Variables in Various Patient Groups
Short Term Outcome after Allogeneic Stem Cell Transplantation in 70 Cases of Severe Aplastic Anaemia.
Authors: Ahmed Parvez , Ullah Khalil , Satti Tariq M. , Raza Shahid , Chaudhry Qamar-Un-Nisa , Kamal Khalid , Khan Badshah , Anwar Masood 
Published: April 2020

Abstract
Allogeneic stem cell transplantation (SCT) from HLA matched sibling donor is the standard treatment option in younger patients with severe aplastic anaemia (SAA). In the current study outcome of 70 patients with SAA undergoing allogeneic SCT at our institution from July 2001 to June 2007 is presented. Median follow up time was 727 days (range 100–2187). Three patients received 2nd SCT due to graft failure or rejection so actual number of SCT in the patients was 73. Median age of the patients was 16 years (range 5–38), 55 males, and 15 females. Seventeen had major ABO mismatch while sex mismatch in the form of female donor to male patient was present in 23 cases, 7 had both major ABO and sex mismatch. Sixty four patients were CMV positive while 6 had CMV negative status. Conditioning regimens included; cyclophosphamide (Cy) 200 mg/kg with either antilymphocyte globulin (ALG) 45 mg/kg (n=33) or antithymocyte globulin (rabbit ATG) 11.25 mg/kg (n=26); Cy plus Campath 100 mg (n=6), fludarabine 150 mg/m2 plus Cy 300 mg/m2 and ATG (n=8). All patient undergoing 2nd transplant received conditioning with Cy, fludarabine and ATG. GVHD prophylaxis was given with cyclosporin (CSA) plus prednisolone (41) with or without short course of methotrexate (29). Patients received PBSC (10) or bone marrow (12) alone or both (48). Mean mononuclear and CD34+ cell doses were 5.59 x 108/Kg and 4.8 x 106/Kg respectively. Median time to neutrophil recovery was 11 days (range 7–24). Neutropenic fever was seen in 60% cases, with mean duration of fever being 8 days. In majority (66%) no focus of infection could be found. Various isolates included gram negative rods (n=6), staphylococcus (n=2) and fungi (n=5). Other post-transplant infections were tuberculosis (n=2), herpes zoster (n=2) and transfusion associated falciparum malaria (n=2). Post-BMT non-infectious complications included acute GVHD (24%), chronic GVHD (08%), hemorrhagic cystitis (14%), seizures (5%), and VOD (3%). Graft rejection and primary graft failure was seen in 3 and 2 cases respectively. Three of them received 2nd transplant and had successful recovery while the other 2 died of septicemia. Six patients died during peri-transplant period, 3 at day 100, and 8 beyond day 100. One patient died of unrelated cause at 2 years post-transplant. Main causes of death were septicemia (n=4), conditioning regimen toxicity (n=3), VOD (n=2), GVHD (n=2) and disseminated aspergillosis (n=2). The overall and disease free survival was 76%. In univariate analysis using Logrank and Wilcoxon test factors correlated with better survival were patient’s age &lt;15 years, disease duration &lt;6 months, previous transfusions &lt;20 events, conditioning with fludarabine/Cy/ATG, and absence of chronic GVHD. SCT from HLA matched sibling donor is effective treatment modality in majority of the young patients with SAA.
A Common Genetic Variant in the 3′UTR of IRF4/MUM1 Associates with Risk of Disease and Poor Prognosis in Chronic Lymphocytic Leukaemia.
Authors: Allan James M , Sunter Nicola , Hall Andrew , Mainou-Fowler Tryfonia , Jackson Graham , Summerfield Geoffrey , Harris Robert John , Pettitt Andrew , Houlston Richard , Bailey James , Pepper Chris , Fegan Chris , Pratt Guy , Allsup David J 
Published: April 2020

Abstract
High frequency low penetrance risk alleles for chronic lymphocytic leukaemia (CLL) have been identified at 6p25.3 (rs872071, IRF4/MUM1), 11q24.1 (rs735665, GRAMD1B), 15q23 (rs7176508), 2q37.1 (rs13397985, SP140), 2q13 (rs17483466, ACOXL) and 19q13.32 (rs11083846, PRKD2). Given a role in determining risk of disease it is plausible that these allelic variants also play a role in disease progression and overall survival. In order to test this hypothesis, polymorphic status was determined in a case series of 403 patients diagnosed with CLL recruited via 5 clinical centres in the United Kingdom. Mean follow-up time was 4447 days and 169 patients were deceased at the time of last follow-up. Kaplan-Meier survival analysis and the log-rank test were used to investigate the prognostic significance of constitutional genetic markers. Polymorphic variation at rs735665, rs7176508, rs13397985, rs17483466 and rs11083846 was not significantly association with time from diagnosis to first treatment (p&gt;0.05, log-rank test). However, a genetic variant in the 3′UTR of the interferon regulatory factor 4 (IRF4)/multiple myeloma oncogene 1 (MUM1) gene was significantly associated with poor prognosis. Specifically, carriers of the disease-associated variant at rs872071 had a significantly shorter mean time from diagnosis to first treatment (3983 days), compared to non-carriers (7340 days)(p=0.001), although there was no significant difference in overall survival (p=0.29). The association with time to first treatment remained significant in multivariate Cox regression analysis that included age, gender, immunoglobulin heavy chain variable region mutational status and stage of disease at diagnosis in the model (p=0.021). IRF4 is expressed in germinal centre (GC) and post-GC B-cells, and is important for B-cell maturation and homeostasis. Taken together with the aetiological evidence, these data suggest that common allelic variation in IRF4 not only affects risk of CLL, but also predicts poor prognosis.