bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer as the Initial Presentation in Patients with Fanconi’s Anemia.
Authors: Alter Blanche P. 
Published: April 2020

Abstract
Background: Patients with Fanconi’s Anemia (FA) have very high risks of developing leukemia and solid tumors. Cancer is thought to follow the diagnosis of FA in most patients, but we know about several patients in whom a cancer diagnosis led to the diagnosis of FA.
Hypotheses: FA patients who present with cancer comprise a substantial proportion of the FA patients who have cancer. Undiagnosed FA may contribute significantly to apparently sporadic cancer patients who are atypically young and lack usual risk factors.
Experimental Design: A systematic review of the medical literature.
Methods: Medline search terms were “Fanconi Anemia” and “Cancer,” “Leukemia” or “Myelodysplastic Syndrome (MDS).” Malignancies after stem cell transplant were excluded.
Results: 90 patients were reported with a solid tumor, 117 with leukemia, and 61 with MDS (11 of whom developed leukemia). These events preceded the diagnosis of FA in ~25% of patients. The median ages at diagnosis of FA were 9, 23, and 12 years respectively. 40% of the tumors were squamous cell carcinomas of the head, neck, or esophagus (HNSCC), and 10% each were brain, Wilms, and gynecologic tumors. The relative frequency of the tumor types was similar whether the first diagnosis was cancer or FA. 90% of the leukemias were acute myeloid leukemia (AML). Among FA patients with tumors as adults (&gt;18 years old), the age at cancer diagnosis was similar whether cancer occurred first or FA was diagnosed first (median ages 31 and 27), but the age at FA was significantly older when cancer came first (32 vs 11 yrs). Among FA patients with tumors &lt;18 years old, those with cancer first had cancer younger than those with FA first (median ages 2 vs 6 years), while the age at diagnosis of FA was similar (2 vs 1 years). In both the &lt;18 and &gt;18 year old patients with leukemia or MDS, these complications occurred at similar ages whether they preceded or followed the diagnosis of FA.
Conclusions: This literature review is limited by over-reporting of patients who presented with cancer and were then identified as FA, and under-reporting of patients who presented with cancer in whom FA was never diagnosed. The magnitude of these biases cannot be determined from the literature, or from cohorts of patients known to have FA. We propose that a systematic evaluation for FA should be done in young, risk-factor negative HNSCC patients, to determine the contribution of FA to this subset of cancer in the general population. Heightened awareness of features of FA may also be helpful in the diagnosis of FA in patients with brain, Wilms, and gynecologic tumors.
A Pilot Study of Rabbit Antithymocyte Globulin - TECELAC Combined with Cyclosporine and Prednisolone as Immunosuppressive Therapy for Severe Aplastic Anemia.
Authors: Chandy Mammen , George Biju , Viswabandya Auro , Bajel Ashish , Mathews Vikram , Srivastava Alok 
Published: April 2020

Abstract
Immunosuppressive therapy is the treatment of choice in patients with severe aplastic anemia (SAA) not eligible for an allogeneic bone marrow transplant. We treated 10 patients with a combination of Tecelac (Biotest, Germany) (1.5 mg/kg/day for 4 days), Cyclosporine (5 mg/kg/day for 6 months) and Prednisolone (2mg/kg/day for 3 weeks and taper over 1 week). Tecelac is a rabbit anti-T cell immunoglobulin produced by Biotest Germany from rabbits immunized with human peripheral blood lymphocytes. Antibiotic and blood product support was given as required. Ten patients (8 males; 2 females) with a median age of 26 years (range: 18–40) were treated. The median time from diagnosis to treatment was 2 months (range: 1 – 4). The median absolute lymphocyte count (ALC) pre ATG was 1537/cumm (range: 1224 – 1748) while the median ALC post ATG was 40/cumm (range: 20 – 200). None of the patients developed serum sickness. Two patients expired due to bacterial infection (Staphylococcal sepsis and Escherichia Coli sepsis) on day +14 and day +40 post ATG. Response was seen in 5(62.5%) out of 8 evaluable patients. Two patients achieved complete normalization of blood counts. Two patients have become transfusion independent for 6 – 12 months of which one had a relapse after 12 months. One patient showed improvement in the absolute neutrophil count (ANC) and platelet count with a decrease in transfusion frequency. Three patients (37.5%) showed no improvement in blood counts and continue to remain transfusion dependant. At a median follow up of 22 months (16 – 30), the overall survival is 80% with a disease free survival of 37%. Rabbit ATG induces remission in a small number of patients with severe aplastic anemia and the results are comparable with some reports using equine ATG/ALG. Larger studies need to be done to evaluate the efficacy of rabbit ATG in severe aplastic anemia.
Management of Hereditary Spherocytosis in a Public Health Care Provider in a Developing Country.
Authors: Feldman Leonardo , Drelichman Guillermo , Basack Nora , Rodriguez Ernesto , Freigeiro Daniel , Aversa Luis 
Published: April 2020

Abstract
Hereditary Spherocytosis (HS) is the most common cause of non-immune hemolytic anemia in Argentine people of European ancestry, it is characterized by chronic hemolysis, which is reduced or abrogated by splenectomy.. Because of the risk of postsplenectomy sepsis, especially among children under 5 years old, partial splenectomy has been advocated as an alternative. This procedure seems to ensure prolonged reduction but not complete elimination of hemolysis and it is possible some regrowth of the splenic remnant and a secondary total splenectomy must be performed in some patients (pts). This problem is worse especially when pts. live in rural areas and a close observation is necessary. We analyzed retrospectively the evolution of 83 pediatric pts with HS with low resources, other health priorities and in some cases an underling nutritional deficit. Diagnostics was made in a public hospital between October 1971 and December 2002 and the last control was in December 2004. The pts. Median age at diagnostic was 4.7 years (14 days to 14 years). Severe forms were observed in 18%, mild in 20% and moderate in 62%. Twenty four pts were phenotypically sporadic. Biochemical analysis (SDS-PAGE) were performed in 30 pts and/or family members, combined spectrin- ankirin deficiency were observed in most of them. Sixty-nine hemolytic crisis was observed in 30 pts (37.5%). and 17.5% developed an aplastic crisis. Fifty-two pts. (65%) received 249 Red Blood Cell Transfusions (Trs), 36% between 1 and 2, 22.5% 3 to10, and 6% between 10 to 34 Trs. Gallstones were observed in 4 PTs (5%). Total splenectomy was performed in 46 of 83 pts (55%), median age: 7 years (4–15) 42 pts had conventional and 4 have undergone laparoscopyc procedure. Ninety six per cent of pts were splenectomized after age of 5. The median time from diagnostic to splenectomy was 1 year (0.2–8.9). All pts were immunized against Pneumococcus, Haemophilus, and Meningococus and received prophylactic antibiotics. With a median follow up of 18.5 years (3–30 y) after splenectomy all pts showed a significant clinical improvement and no further transfusion requirement. In all cases the hemoglobin increased (median pre and post splenectomy 8.6/13gr/dl) and reticulocyte counts decreased (8 / 1.4%). We do not observe procedure relate mortality, sepsis, thrombosis, and aplastic or hemolytic crisis post-splenectomy. On the basis of our experience we favor the total splenectomy performed by a training team in countries with low resources and in pts with deficient hygienic and housing conditions that inhabit in places with long distances from centers to ensure wider access to training health care providers.
Subsets and Function Changes of Th Cells in the Bone Marrow of Patients with Immune Related Pancytopenia.
Authors: He Guangsheng , Wang Xiuli , Wu De Pei , Sun Aining , Jin Zhengming 
Published: April 2020

Abstract
Objectives
To explore the subsets and function of T helper (Th) in bone marrow of the patients with immune related pancytopenia(IRP).
Methods
The CD4+ cells producing IFN-γ or IL-4 in cytoplasm were defined as Th1 or Th2 cells respectively. All these cells in bone marrow were measured from 16 normal controls, 25 untreated IRP patients; The mRNA expressions of IL-4, IL-10, IFN-γ and IL-2 genes in unstimulated bone marrow mononuclear cells(BMMNC)from 25 untreated IRP patients, 10 normal controls were measured by reverse transcription polymerase chain reaction (RT-PCR).
Results
The percentage of Th1 cells, Th2 cells and ratio of Th1/Th2 in bone marrow of normal controls was: 0.42%, 0.24%, 1.57 respectively, and the percentage of Th1 cells in untreated patients with IRP was 0.58%, which was not markedly different from the that of normal controls(t=0.903, P&gt;0.05). But the percentage of Th2 cells of the patients with IRP was significantly higher than that of normal controls(t=4.673, P&lt;0.01), and the balance of Th1/Th2 shifted to Th2 more significantly by comparing to that of normal controls (t=4.880, P&lt;0.01). The mRNA expressions of IL-4 and IL-10 in the Th2 cells of the untreated IRP patients were significantly higher than those of the normal controls, however difference of the expressions of IFN-γ and IL-2 in the Th1 cells were not significantly.
Conclusions
The percentage of Th2 cells increased in the patients with IRP, and the balance of Th1/Th2 shifted to Th2. And the expression of Th2 type cytokines was more frequent in IRP. The imbalance of subtypes of Th lymphocytes and hyperfunction of Th2 lymphocytes might play important roles in the pathogenic mechanism of IRP, which lead to more B lymphocytes and producing autoantibodies consistenly.
The Association between Serum Copper and Anemia in the Adult NHANES II Population.
Authors: Molnar Istvan , Il’yasova Dora , Ivanova Anastasia , Knovich Mary A. 
Published: April 2020

Abstract
Anemia is prevalent in older adults. Although the majority of cases are due to nutritional deficiencies, chronic inflammation, or renal disease, anemia remains unexplained in about one third of cases (Guralnik et al., Blood, 2004, p2263). Copper deficiency has been reported as a rare cause of anemia and neutropenia. We hypothesized that copper deficiency could account for some cases of unexplained anemia in adults. To test this hypothesis, we examined the relationship between serum copper and unexplained anemia in 11,240 adults (15 years and older) who participated in the Second National Health and Nutrition Examination Survey (NHANES II). Anemia was defined as hemoglobin level below 13.5 g/dL in males and below 11.5 g/dL in females. In this study population, 638 or 5.7% of adults were anemic. Of these, anemia was unexplained by vitamin B12, folate, or iron deficiencies, chronic inflammation, or renal disease in 421 or 3.7% of the total subjects studied. Thus, unexplained anemia constituted approximately 65% of all anemia cases in this sample of US adults.
Median serum copper level was significantly higher in all anemia cases (126 μg/dL, p &lt;0.0001), in explained anemia (133 μg/dL, p&lt;0.0001), and in unexplained anemia (122 μg/dL, p&lt;0.02) as compared to non-anemic adults (119 μg/dL, ref). Spline regression showed a U-shaped relationship between serum copper levels and unexplained anemia. The prevalence of unexplained anemia increased significantly at both lower and higher copper levels as compared to the median (119 μg/dL): odds ratios for unexplained anemia were 1.2 (95% CI: 1.1–1.3) in the association with a decrease of serum copper from median to 10th percentile (92 μg/dL) and 1.8 (95% CI: 1.6–2.2) in the association with an increase of serum copper to 90th percentile (161 μg/dL).
This study likely underestimates the prevalence of anemia of chronic illness, as only a single marker of inflammation (serum iron) was available to capture these subjects. Furthermore, copper levels are known to be elevated in inflammation. Thus, unrecognized cases of anemia of chronic illness might explain the observed association between high serum copper levels and unexplained anemia. On the other hand, subjects with low serum copper levels and unexplained anemia might have nutritional deficiency.
In conclusion, this analysis of the NHANES II data confirms (1) that unexplained anemia is common among the US adults, and (2) that both lower and higher than median serum copper levels are positively associated with unexplained anemia. These findings support the need for further study of copper status in adults with unexplained anemia.
Randomized, Open-Label Study of Epoetin alfa 40,000 U Once Weekly Versus 80,000 U Every Two Weeks in Anemic Patients with Cancer Receiving Chemotherapy.
Authors: Henry David H. , Xie John , Woodman Richard C. 
Published: April 2020

Abstract
Epoetin alfa administered three times weekly or once weekly (QW) has been proven and widely accepted in the management of chemotherapy (CT)-induced anemia. Extended dosing intervals less frequent than QW would provide added convenience for patients. An ongoing randomized open-label study was designed to compare the efficacy and safety of a regimen of 80,000 U of epoetin alfa every two weeks (Q2W) to the commonly used regimen of 40,000 U QW. Two hundred and eighty patients with nonmeyloid malignancy, baseline (BL) hemoglobin (Hb) ≤ 11 g/dL, and scheduled to receive CT for a minimum of 12 weeks will be enrolled. Doses will be adjusted to maintain Hb values of approximately 12 g/dL. Endpoints include the comparison of change in mean Hb values at the end of the study (EOS) between the two treatment groups and Hb over time. The first 71 randomized patients (mean age 64 years, 72% women, 31% breast cancer) with at least one post-BL Hb or transfusion were analyzed. Preliminary results (see table) demonstrate similar Hb increases for each group. In the QW group, 50% (10/20) of patients and in the Q2W group 76% (16/21) of patients had ≥ 1 g/dL Hb increase during the first 4 weeks. Five (14%) QW and 7 (20%) Q2W patients had a serious adverse event; no clinically relevant thrombovascular events were reported; 1 patient (QW) died on study. These results suggest that initiating epoetin alfa treatment for CT-induced anemia with 80,000 U every two weeks provides similar efficacy and safety as treatment with 40,000 U weekly.
Mean Hb Over Time Epoetin alfa 40,000 U QW Epoetin alfa 80,000 U Q2W Weeks on Study Mean ± SD (N) Mean ± SD (N) BL 9.9 ± 0.9 (36) 9.8 ± 0.9 (35) 4 11.0 ± 1.2 (20) 11.2 ± 1.2 (21) 6 10.9 ± 1.4 (13) 11.0 ± 1.5 (18) 8 10.7 ± 1.3 (7) 11.7 ± 1.6 (11) 12 (EOS) 11.6 ± 1.1 (3) 11.1 ± 1.1 (5)
A Randomized Controlled Trial of Patient Controlled Analgesia Versus Continuous Infusion of Morphine during Vaso-Occlusive Crisis in Sickle Cell Disease.
Authors: van Beers Eduard J. , Nieuwkerk Pythia T. , van Tuijn Charlotte F.J. , Friederich Philip W. , Vranken Jan H. , Biemond Bart J. 
Published: April 2020

Abstract
Pain during vaso-occlusive crisis (VOC) in sickle cell disease (SCD) is commonly treated with continuous intravenous infusion (CI) of morphine. During CI the treating physician titrates the dose of morphine until adequate relief of pain has been established. Patient controlled analgesia (PCA) allows the patient to self-administer doses of morphine for the relief of pain and has shown to be equianalgesic in post surgical patients with lower morphine consumption than with CI of morphine. Morphine has many dose-related side-effects and high plasma levels of morphine are associated with serious complications. Therefore, we conducted the first randomized controlled trial to compare the administration of morphine with PCA versus CI in sickle cell patients with VOC. 26 consecutive episodes of VOC in 21 patients with SCD were included. Patients were randomized between PCA and CI of morphine within 24 hours after hospital admission. Endpoints of the study were: the mean and cumulative morphine dose, pain intensity and quality of life (QoL). Pain intensity was measured daily using a ten-point-scale verbal pain score. Reduction of pain intensity was measured by subtracting a pain score on a ten point visual analogue scale (VAS) before randomization from the same measurement two days after randomization. QoL was measured using the Medical Outcomes Study 36-item Short Form Healthy Survey (SF36).
Patients with PCA demonstrated to have significant lower morphine consumption as compared to patients randomized to CI. The mean and total cumulative morphine dose was 0.5 mg/h and 33 mg in the PCA-group versus 2.3 mg/h and 275 mg in the CI-group, respectively (p=0.02 and p&lt;0.001). The pain intensity was not different between the groups. The mean daily ten-point-scale verbal pain score was 5.1 in the PCA group versus 5.3 in the CI-group (p=0.20). Reduction in pain intensity (VAS) two days after randomization was −2.4 in the PCA-group versus −3.8 in the CI-group (p=1.00). Also no difference in QoL was found.
We conclude that the use of PCA in sickle cell patients with VOC results in adequate pain relief at a significant lower morphine dose as compared to morphine administration by continuous infusion.
Figure. Mean morphine dose per patient Figure. Mean morphine dose per patient
Cancer Incidence in Sickle Cell Disease. Howard University, 1996–2004.
Authors: Dawkins Fitzroy , Ufearo Hilary , Pantin Jeremy , Kwagyan John , Nwokolo Catherine , Onyekwere Onyinye C. , Gordeuk Victor R. , Castro Oswaldo 
Published: April 2020

Abstract
There are no prospectively collected data on cancer incidence and mortality in patients with sickle cell disease. This information would be a useful baseline for cancer surveillance, particularly in sickle patients exposed to potentially carcinogenic interventions such as hydroxurea administration and stem cell transplantation. A review of cancer cases among 696 adult sickle cell patients (mean age 28.8 y) at Howard University for the years 1986–1995 (2,684 patient-years, pt. yrs.) estimated the cancer incidence and mortality at 1.74 and 1.04 per 1000 pt. yrs, respectively (Am J Hematol1997;55:188). These figures were comparable to those reported for adult African American patients of similar age in the SEER database.
Because sickle cell patients are now surviving longer, we examined again the cancer incidence and mortality at our institution for the years 1996 – 2004. In determining the patient-years of observation we assumed that if a patient was seen at least once during a given calendar year, the patient had been observed for that whole year. A total of 677 adult sickle cell patients (mean age 35.1 ± 12.5 y) were followed from 1996 through 2004 (2,317 pt.yrs.). There were 54.5 % females and 45.5 % males; the Hb genotype distribution was SS=70.5%, SC=19.2%, S-Thal=9.7%, and other=1%. The table shows the characteristics of 7 sickle cell patients who developed cancer during the study period. Their ages ranged between 38 and 64 years. All but one (Pt. 7) were female and all but one (Pt. 2) had Hb SS. Patients 1 and 3 had been treated with hydroxyurea.
Based on these cases, the estimated cancer incidence was 3.02 per 1000 patient years, still below the upper 95% confidence limit in the 1986–1995 estimate (4.3 per 1000 patient years). Two additional cancer patients were seen at our institution, one with prostate cancer and the other with metastatic breast cancer. They were not included in the incidence estimate since they were specifically referred to our institution because of the cancer diagnosis. The current incidence of cancer in adult sickle cell patients at our institution is not increasing appreciably even though they are getting older and some are taking hydroxyurea.
Patient Age (y) Sex Hb type Cancer type 1 43 F SS Cervical carcinoma in situ 2 38 F SC Hodkin’s disease 3 64 F SS Uterine carcino-sarcoma 4 43 F SS Metastatic adeno-ca., primary unknown 5 57 F SS Renal adenocarcinoma 6 48 F SS Breast cancer 7 38 M SS Anaplastic B-cell lymphoma (HIV)
Painful Episodes in Children with Sickle Cell Disease and Asthma Are Temporally Associated with Respiratory Symptoms.
Authors: Glassberg Jeffrey A. , Spivey John F. , Strunk Robert , Boslaugh Sarah , DeBaun Michael R. 
Published: April 2020

Abstract
Background: Previously our research group demonstrated that a diagnosis of asthma is associated with an increased rate of painful episodes in children with sickle cell disease (SCD); however, little is known about the temporal relationship between an asthma exacerbation and a painful episode in a child with SCD. We tested the hypothesis that respiratory symptoms either precede or occur concomitantly with painful episodes more frequently in children with SCD and asthma when compared to children without asthma.
Methods: As part of standard care, a cohort study was conducted. The primary hematologist referred all children with SCD for evaluation by a pulmonologist. The definition of asthma was based on the National Heart Lung and Blood Institute’s guidelines. The primary outcome recorded was respiratory symptoms occurring up to 96 hours prior to a painful episode. Respiratory symptoms were defined as any of the following:
cough wheeze tachypnea retractions, or grunting.
Pain was defined as the complaint of body pain (excluding the head) requiring the administration of opioids in the hospital, clinic, or emergency department.. Cases and controls were children with and without asthma, respectively. Medical records from all hematology clinic, emergency department, and inpatient visits over a 25-month period were reviewed for painful episodes and the presence of respiratory symptoms.
Results: A total of 74 children were evaluated by a hematologist and referred to pulmonologist for an asthma between 6/15/2004 and 1/31/2005. Of the eligible patients, 36 were diagnosed with asthma (mean age 9.8 years; median 9.6 years; range 2.4–19.4) and 38 were determined not to have asthma (mean age, 9.8 years; median 9.7 years; range 2.4–19.5). For children with asthma versus those without asthma, the odds ratio of having a pain episode associated with antecedent or concurrent respiratory symptoms was 4.9 (95% confidence intervals, 2.2–10.7).
Conclusions: In children with both SCD and asthma, respiratory symptoms are a risk factor for subsequent painful episodes.