bluuebunny/crossref_metadata_2025 huggingface dataset:
High Dose Chemotherapy with Autologous Stem Cell Transplant in Treatment of Germ Cell Tumors: A Systematic Review and Meta-Analysis
Authors: Husnain Muhammad , Riaz Irbaz Bin , Kamal Muhammad Umar , Gondal Farva Razia , Ali Zeeshan , Sipra Qurat-ul-Ain Riaz , Javed Asad , Akbar Sara , Singh Parminder , Anwer Faiz
Published: November 2019

Background:

Cure rates for the poor risk, relapsed and refractory germ cell tumors are only 25 % with conventional dose chemotherapy. High Dose Chemotherapy (HDCT) followed by rescue stem cell transplant has since been studied in randomized controlled trails for the IGCCG poor risk group patients and for the relapsed and refractory testicular cancer patients. We conducted a meta-analysis of all prospective Phase II and III trials studying the role of high dose chemotherapy in germ cell tumors.

Methods:

Literature search was conducted using methods described in the PRISMA statement. Medline (PubMed and Ovid SP), Embase, Cochrane Central Register of Controlled Clinical Trials(CENTRAL) and Cochrane Database of Systematic Review (CDSR) were searched from the inception of these databases till present. We performed a meta-analysis using Comprehensive Meta-analysis 3.0 using random effects model. The heterogeneity was assessed using I2values and sensitivity analysis was performed to explain the heterogeneity where present.

Results:

After a comprehensive literature search 4440 studies were identified and finally 35 studies were included in the final analysis. 14 studies involving 905 patients with IGCCG poor risk germ cell cancer were treated with high dose chemotherapy. 44 % (398) patients were able to achieve CR with HDCT with HR of o.48 (0.33-0.62) p=0.75. The overall survival (OS) and Progression free survival (PFS ) were 0.62 (0.54-0.69, p=0.004) and 0.60 (0.52-0.68 p=0.011) respectively.

21 studies involving 1153 patients with relapsed and or refractory germ cell cancer were identified. CR rate with HDCT was 32 % (374 patients) with HR of 0.32 (0.26-0.40, p=0.00). The results for OS failed to show any significant results with HR of 0.52 (0.44-0.60, p=0.67) but was significant for PFS with HR of 0.60 (0.52-0.67, p=0.01).

Conclusion:

High dose chemotherapy followed by HSCT showed significant OS and PFS for IGCCG poor risk category germ cell tumors and significant CR and PFS for relapsed and or refractory germ cell cancer group.

Disclosures

Anwer: Incyte: Speakers Bureau; Seattle Genetics: Other: Advisory Board Participant.
Outcomes of Hematopoietic Stem Cell Transplant in Older Patients with Myelodysplastic Syndrome and Co-Existing Myelofibrosis: A Single Center Experience and Review of the Literature
Authors: Saste Abhijit B , Kuriakose Philip , Janakiraman Nalini , Peres Edward , Farhan Shatha Y.
Published: November 2019

Background:Myelodysplastic syndrome with coexisting bone marrow fibrosis has a dismal prognosis when treated with conventional chemotherapy suggesting that marrow fibrotic grade may be an important prognostic factor. Allogeneic stem cell transplantation (ASCT) has been utilized in young fit patients with this disorder. However outcomes in older patients are unknown.

Design and Methods: We conducted a retrospective study to assess the therapeutic efficacy of ASCT in 11 patients with myelodysplastic syndrome with a known co-existing high grade myelofibrosis (n=11) .Data were classified based on cytogenetic risk, conditioning regimen, donor source and cytoreduction pre-transplant. We evaluated rates of engraftment, graft versus host disease and overall survival.

Results : Higher median age of 66 years, high cytogenetic risk class and high grade bone marrow fibrosis in our study population was not associated with inferior survival in a univariate analysis. There were no patients who developed graft failure. Cumulative incidence of engraftment achieved at day +30 based on chimersim was 72.7%. The 3 year overall survival was 100% when pre-transplant cytoreduction was used. There were no cases of disease relapse.

Conclusions : Among patients with myelodysplastic syndrome and concomitant bone marrow fibrosis, advanced age, a higher grade of fibrosis or cytogenetic complexity did not adversely affect survival after ASCT.This treatment modality should therefore be considered in patients even with advanced age.

Disclosures

No relevant conflicts of interest to declare.
Antithymocyte Globulin Improves the Survival of Patients with Myelodysplastic Syndrome Undergoing HLA-Matched Unrelated Donor and Haplo-Identical Donor Transplants
Authors: Miao Miao , Wang Hong , Liu Hong , Zhou Jinyi , Zhang Tongtong , Jin Song , Zhang Xiang , Chen Suning , Li Weiyang , Xu Yang , Wu Depei
Published: November 2019

Background: Significant advances have been achieved in the outcomes of patients with myelodysplastic syndromes (MDS) after both HLA-matched sibling donor transplants (MSDT) and non-MSDT in the past few years, the latter including HLA-matched unrelated donor (MUDT) and haplo-identical donor transplants (HIDT).

Methods: We retrospectively analyzed the data of 85 consecutive patients with MDS who received allogeneic HSCT between Dec 2007 and Apr 2014 in our center. These patients comprised 38 (44.7%) who received MSDT, 29 (34.1%) MUDT, and 18 (21.2%) HIDT.

Results: The median follow-up was 30.0 months. Over all, the median overall survival (OS) was 60.2 months and the probabilities of OS at the first, second and fifth year were 63%, 57% and 48%, respectively. Median OS post transplant (OSPT) was 57.2 months and the probabilities of OSPT at the first, second and fifth year were 58%, 55% and 48%, respectively. Relapses occurred in 16 patients (18.8%), and the cumulative incidence of relapse at the first, second and third year were 14%, 23% and 27%, respectively. The survival of patients receiving non-MSDT was superior to that of MSDT, median OSPT being 84.0 months and 23.6 months, respectively (P=0.042);

And the similar result was observed when we analyzed the OS of patients who underwent non-MSDT or MSDT (median OS: 120 months vs. 27.0 months; P=0.028). We also found that using antithymocyte globulin (ATG) in conditioning regimens significantly improved survival after non-MSDT, with better OS and OSPT (P=0.016 and P=0.025). Furthermore, we compared OS or OSPT of patients who received non-MSDT with ATG (n=38) and MSDT without ATG (n=37). Our results showed that using ATG in conditioning regimen significantly improved survival of non-MSDT, with better OSPT (median OS: 84.0 months vs. 23.0 months; P=0.026) and OS (median OS: 120 months vs. 25.1 months; P=0.016).

Conclusions: These data suggest that, non-MSDT could be a valid alternative when MSDT is not available, and ATG may improve the survival of MDS patients after non-MSDT.

Disclosures

No relevant conflicts of interest to declare.
Autoimmune Hematological Diseases Following Haploidentical Donor Hematopoietic Stem Cell Transplant Compared with Matched Sibling and Unrelated Donor
Authors: Lv Weiran , Liu Qifa , Fan Zhiping , Huang Fen , Xu Na , Xuan Li , Yu Guopan , Jiang Qianli , Zhou Hongsheng , Lin Ren , Sun Jing , Zhang Xin
Published: November 2019

Objective:Autoimmune hematological diseases (AHDs) occur more frequently than other autoimmune complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and are often refractory to treatment. The aim of this study was to analyze the incidence and risk factors of AHDs as well as its response to treatment in a series of patients undergoing allo-HSCT at our single institution.

Method:Forty hundred and forty-five adult malignant hematopoietic disorders underwent allo-HSCT were enrolled in this retrospective study, including 181 cases underwent HLA-matched sibling donor (MSD) transplants, 140 unrelated donor (MUD) transplants and 124 haploidentical donor transplants (HRD).

Result:Twelve patients developed AHDs, including 6 autoimmune hemolytic anemia (AIHA)and 6 Evans' syndrome.The median time of AHDs onset was 196 days (range, 60-756). Evans' syndrome all ocuured in HRD. The 3-year cumulative incidence of AHDs was 2.7%,and HRD had higher incidence than MSD (6.5% vs 1.1%,P=0.017) and MUD(6.5%vs1.4%,P=0.049). Eight of them received complete response (CR) and 3 no response (NR) after 11 patients received the corticosteroids combined with CSA as the initial treatment for 4 weeks. One obtained CR and 2 PR after 3 NR cases treated by rituximab. Eleven cases all not were AHDs recurrence at a median followup of 313 days (range, 153 to 1051 days after CR. HRD transplantation(vs MSD: hazard ratio [HR], 7.70; 95% confidence interval [CI], 1.63 to 36.44; P=.01 and vs MUD: hazard ratio [HR], 5.87; 95% confidence interval [CI], 1.24 to 27.73; P=.026) and concurrent chronic GVHD (hazard ratio [HR], 3.76; 95% confidence interval [CI], 1.18 to 11.92; P=.025)were risk factors for AHDs.

Conclusion:The patients undergoing HRD transplantation had higher risk of AHDs and manifested as Evan's syndrome was very common compared with MSD and MUD. Corticosteroids combined with CSA as the first line treatment of AHDs results in good response and low recurrence rate.

Disclosures

Lin: National Natural Science Foundation of China 81400141: Research Funding; National Natural Science Foundation of China 81270647: Research Funding; Science and technology planning project of Guangdong Province 2014B020226004: Research Funding; The project of health collaborative innovation of Guangzhou City 201400000003-4: Research Funding.
Feasibility and Outcome of Hematopoietic Stem Cell Transplantation Combined with Decitabine for Children with Juvenile Myelomonocytic Leukemia
Authors: Liu Huaying , Li Chunfu , He Yuelin
Published: November 2019

Background

Juvenile myelomonocytic leukemia(JMML) is a rare clonalmyelodysplastic/myeloproliferative disorder that occurs during infancy and early childhood with poor prognosis. Chemotherapy has not been found to be dffective, and Hematopoietic stem cell transplantation(HSCT) is currently the only curative treatment for JMML. Relapse and engraftment failure are the major causes of HSCT failure in JMML.

Patients and method

We report the outcomes of 4 patients with JMML who received HSCT combined with Decitabine between 2014-2015. Patient median age was 2 years(range,1-3years), and 3 were boys and 1 girl. Decitabine was given before and after the HSCT for one time(20mg/m2.d X 5d、10mg/m2 .d X 5d). Before HSCT, all the patients received mild chemotherapy(three or four course). The bone marrow evaluations of all the patients before HSCT were complete remission(CR). Two patients received human leukocyte antigen(HLA)-matched HSCT from unrelated donors, and two patients received haploidentical HSCT from parents followed by unrelated cord blood transplantation(UCB). Conditioning regimen of Unrelated donor-PBSCT was Busulfan+fludarabine+Thiotepa+Thymoglobuline, and the conditioning of haplo-HSCT was Busulfan+fludarabine+Cytarabine+Thymoglobuline. The number of nucleated cells of HLA-matched HSCT was 8×108/kg. The number of nucleated cells of Haplo-HSCT was 47.2×108/kg、61.26×108/kg , respectively, and the number of nucleated cells of UCB was 7.23×107/kg、9.4×107/kg, respectively. GVHD prophylaxis was based on post-transplant high-dose cyclophosphamide(PTCy, 50mg/kg on days +3 and +4) combined with mycophenolate plus cyclosporine A or tacrlimus.

Results:

The median follow-up was 21 months(range,11-27 months). The overall survival(OS) and the Disease free survival(DFS) both were 100%, All the patients got 100% engraftment(Unrelated-donor stem cell engrafted and Haploidentical-donor stem cell engrafted in 2 and 2 patients , respectively). None of the patients developed relaps, the bone marrow evaluations were complete remission(CR) after HSCT. The most common toxicities were infection with neutropenia(100%, n=4), The cumulative incidences of acute GVHD gradesII-III and CMV infection were 50% and 75% respectively.

Conclusion:

The combination of decitabine and HSCT shows encouraging results with highly effective and less toxicity for JMML. The futhuer study should be developed in the future.

Disclosures

No relevant conflicts of interest to declare.
Triterpene Glycosides from Cimicifuga FoetidaRegulate wnt/β-Catenin Signaling in Human KG-1a Leukemia Cells
Authors: Xu Rui-Rong , Cui Si-Yuan , Chen Chong , Jiao Ning , Wu Xiao-Long , Wang Xin , Qiu Ming-Hua
Published: November 2019

Background : Leukemia stem cells (LSCs) are a limitless cell source for the initiation and maintenance of leukemia. Activation of the Wnt/β-catenin pathway is required for the survival and development of LSCs. Therefore,targeting β-catenin is considered a therapeutic strategy for the treatment of leukemia. The goal of this study was to explore whether Triterpene Glycosides(A, DA and KCY4),the active components of the traditional medicine Cimicifuga foetida, regulate β-catenin expression in leukemia cells.

Methodology and Principal Findings: Triterpene glycosides(A, DA and KCY4) from Cimicifuga foetida, which grow in black stone town in Guizhou, had been isolated and reported their molecular structure and anti-tumor activity. In this study, we injected KG-1a cells into NOD/SCID mice to establish animal model of acute myelogenous leukemia(AML), and intervened model by three kinds of triterpene glycosides(A, DA and KCY4). Observing mice living conditions, cell cycle and apoptosis rate were analyzed by flow cytometry (FCM), meanwhile, protein expression changes of β-catenin, APC and cyclinD1 were tested by immunohistochemistry (IHC). The results demonstrated the function of medium concentration of triterpene glycosides against AML KG-1a cells was induced by self-renewal of Wnt/β-catenin signaling pathways in LSCs G1 arrest and apoptosis. Apparently, mediating the induction of expression of two key factors (APC and CyclinD1) could effect expression of β-catenin. It may play an important role in induction of G1 arrest and apoptosis by the self-renewal of Wnt/β-catenin signaling pathways.

Significance: Our findings show for the first time that Triterpene glycosides(A, DA and KCY4) from Cimicifuga foetida selectively reduces β-catenin stability in AML KG-1a cells. This suppressive effect is mediated by regulating APC and CyclinD1. The effect of KCY4 is more powerful than that of A or DA.KCY4 is likely to be used as a novel strategy to eradicate leukemia via elimination of LSCs.

Disclosures

No relevant conflicts of interest to declare.
"Osteonecrosis of Jaw (ONJ) after Bisphosphonate Treatment in Patients with Multiple Myeloma (MM) : Monocentric Experience of Decreasing ONJ Incidence after Preventive Measures."
Authors: Catania Gioacchino , Monaco Federico , Ladetto Marco , Pepe Paola , Limberti Giulia , Alessio Manuela , Baraldi Anna , Fasciolo Antonella , Fusco Vittorio
Published: November 2019

Disclosures

No relevant conflicts of interest to declare.
Taking "Cellfies": Blood Morphology in the Era of Smartphones
Authors: Fountzilas Christos , Le Isabelle , Mazo-Canola Marcela , Bowhay-Carnes Elizabeth , Karnad Anand
Published: November 2019

Background: Microscopic examination of blood and marrow smears by hematologists is an essential clinical skill at risk of extinction in this high-tech era. This skill is on the decline being replaced by the reliance on flow cytometry, FISH, and molecular diagnostics. Five years ago, we observed that photographs of the oil-immersion field (OIF) in focus could be taken by positioning the smartphone camera lens close to either eyepiece. The captured image could be viewed on the smartphone, swiped to view detail, stored, and shared. We coined the term "Cellfie" for this smartphone image of the OIF. Cellfies can be taken with any smartphone at any microscope, with most learners taking a few minutes for their first Cellfie, and experts able to take Cellfies in a few seconds. Since 2012, we have taught fellows to use Cellfies at the microscope in the hospital and in clinic, and we present the experience of our hematology fellows using Cellfies.

Methods: We surveyed past and current hematology fellows (Class of 2015-to Class of 2019) regarding their experience with Cellfies.

Results: Nineteen of the twenty fellows invited to participate in the survey responded (95%). Two were PGY IV, 4 were PGY V, and 6 were PGY-VI. Four were fellows who graduated and in practice for one year (3 fellows did not provide level of training). Fifteen of 19 fellows (79%) had taken a Cellfie at some point during their training. Five took <10 Cellfies, 4 took 10-20 Cellfies, and one fellow had taken 50 or more Cellfies. Eight (53%) fellows rated the technique as 'easy', and 6 as 'difficult' (40%); one patient found the technique 'very difficult'. Cellfies were commonly used for consultation (80% of responders) and morphology teaching or use in conferences (67%). Only 2 responders had ever used Cellfies to paste in the electronic medical record (EMR). Overall, 80% of the responders thought Cellfies as a very useful tool in their everyday hematology practice.

Conclusion: Cellfie use by hematology fellows has resurrected this essential clinical skill of expertise in blood morphology. We have found a way to rekindle a passion for morphology and renew enthusiasm amongst hematology fellows, residents, and students to use information from microscopy as an essential component of their clinical skills. Taking and sharing Cellfies has the potential to put microscope skills back at the bedside, enable rapid diagnosis and treatment, shorten time to intervention in emergencies (acute promyelocytic leukemia, microangiopathy syndromes for example), expedite consultation after-hours and weekends, improve the quality of documentation in EMRs, create a portfolio of stored images for review, and teaching, and enhance patient-care.

Disclosures

No relevant conflicts of interest to declare.
The Real World of Arsenic Uses in Chinese with Acute Promyelocytic Leukemia: A Cross-Sectional Survey
Authors: Zhu Hong-Hu , Zheng Feng-Mei , Huang Xiao-Jun
Published: November 2019

OBJECTIVE:

Arsenic has become first-line treatment of acute promyelocytic leukemia (APL) since 2013 according to NCCN Guidelines Acute Myeloid Leukemia Version 2.2013, but little information is available about the real world of arsenic uses in China. We aimed to evaluate the usage of arsenic and assess the current status of the treatment of APL in China.

METHODS:

Noninterventional, cross-sectional survey using electronic questionnaires distributed to APL patients and answered anonymously.

RESULTS:

In total, 237 respondents were evaluable and 120 respondents (50.6%) were male. Median age was 40 years (range 15-68 years). Median time from diagnosis to this survey was 15 months. Valid submissions came from 28 of 34 provinces and municipalities. There were 77.64% respondents hospitalized within three days since diagnosis. The percentage of respondents received arsenic during induction treatment was 73.8% (175/237), including arsenic trioxide (ATO) (n=136) and oral arsenic (n=39). However, the percentage increased up to 100% (237/237) during the post-remission treatment phase, including ATO (n=137) and oral arsenic (n=100). Interestingly, 32.9% respondents considered the costs of ATO acceptable by themselves. However, 92.4% respondents regarded the burden of oral arsenic was high because it was not covered by health insurance, and 95.8% respondents appeal to oral arsenic covered by health insurance. The proportion of respondents covered by Basic Insurance for Urban Employees, Basic Insurance for Urban Residents, the New Rural Cooperative Medical Scheme and Commercial insurance were 3.8%, 44.3%, 38.4% and 5.9%. In total, 99.16% respondents hope to receive a chemotherapy-free outpatient treatment protocol

CONCLUSIONS:

High proportion of APL patients received arsenic as first-line treatment in China, which may result from the relative low price of arsenic. A chemotherapy-free outpatient treatment model worthy to explore.

Disclosures

No relevant conflicts of interest to declare.
Patient-Reported Symptoms in the Hematologic Malignancies
Authors: Crilley Pamela Ann , Albu Daniela , Denny Diane , Topolsky David , Bosch Brandon , Parikh Ankur , Hartman Scott , Markman Maurie
Published: November 2019

BACKGROUND : In patients with hematologic malignancies symptoms related to the disease and its treatment remain a major problem in patient care. With the advent of new treatment including immunotherapy and targeted therapies the potential for prolonged life and additional treatment is increasing. Patient self-reported symptom burden during periods of observation and treatment are infrequently reported but highly relevant to patient care. Assessment of patient-reported outcomes may allow for improvement in the management of symptoms and communication with providers.

The Symptom Inventory Tool (SIT) is an assessment tool that captures patient's perceived symptom burden for real-time clinical intervention, taken at baseline and every 21 days or greater. It is comprised of 19 questions from the validated M.D. Anderson SIT (MDASI) (Cleeland CS, Cancer 2013.) and 8 additional questions added by CTCA for additional evaluation of patient symptoms.

PATIENTS & METHODS:

Patients reported symptoms intensity using the SIT: 19-item MDASI and 8 additional questions added by CTCA (constipation, swelling, mouth soreness, bleeding, sexual interest, family, hope & overall QOL). Symptoms were rated "at the worst" on an 11-point numeric scale ranging from 0 ('none present") to 10 ("as bad as you can imagine") in the previous 24 hours. SIT became an integral part of patient care at CTCA beginning in 2012.

RESULTS: From 2012 to 2016, a total of 230 patients diagnosed with hematologic malignancies were evaluated at CTCA-ERMC. 108 patients that had two or more SIT data points were selected for analysis. A total of 830 assessments were analyzed. The assessments consisted of 108 completed at baseline, 107 completed at the 2nd follow-up, and 613 at 3rd follow-up or greater. Median age was 51 years (range, 18-78). Race: white (65%) black (32%) and other (2%). The average time since diagnosis was 41 months, and 32% of the patients had received prior systemic therapy. Table 1 shows the 5 most reported symptoms of entire sample with approximately 30% reported improvement from the baseline to the second assessment. Table 2 shows a subset of 35 patients that reported severe scores of > 8 for five symptoms that had clinically significant improvement from baseline to 2nd assessment.

CONCLUSIONS: The SIT was successful in identifying symptom burden and interference with life issues in patients with hematologic malignancies. Early identification of patient symptom burden may allow for faster intervention and improvement in patient outcomes.

Disclosures

No relevant conflicts of interest to declare.
THE ADHESION OF DOG PLATELETS TO BACTERIA
Authors: HOULIHAN RALPH B.
Published: November 2019

Streptococci and staphylococci, when added to platelet-rich plasma, serum, and defibrinated blood of the dog, are quickly enmeshed by large clumps of platelets. The factor responsible for this reaction is present in the plasma. It is heat-labile, is inactivated by adsorption with Kieselguhr and bacteria, and is partially inactivated by shaking. The activity of this factor is depressed in the presence of sodium citrate.
STUDIES ON PLATELETS
Authors: COPLEY ALFRED L. , HOULIHAN RALPH B.
Published: November 2019

1. Two methods for the isolation of platelets are described in detail. Employing both methods, 55 isolations were made from 31 human beings and 20 isolations from 20 dogs. Both methods are based on the principle of using the platelet layer obtained by repeated fractional centrifugation.

2. The Blood Anticoagulant Platelet Isolation (A) differs from the Blood Saline Platelet Isolation (B). In Method A the following anticoagulants were used: sodium heparin, in various concentrations; sodium citrate; sodium oxalate; and magnesium sulfate. In Method B 10 to 15 parts of saline were added to 1 part blood to keep the blood incoagulable.

3. Special Platelet Isolation (P-I) tubes were designed to isolate the platelets in the final steps.

4. In both methods the platelets were washed with chilled 0.9 per cent sodium chloride solution. The final platelet suspension in saline was obtained free from red and white cells and plasma after six to seven centrifugations and washings.

5. Method A has the advantage of being less laborious. Method B may be preferred for studies of platelets obtained without anticoagulants.

6. The approximate platelet yield in each method varied greatly. It was found that high concentrations of heparin did not produce the highest yields of platelets.

7. Decreases of more than 25 per cent of the initial count were considered significant. The platelets isolated from blood containing sodium heparin, sodium citrate, and sodium oxalate did not significantly decrease in number following storage for a fairly long time. However, platelets isolated using magnesium sulfate and saline did decrease significantly after one to three days’ storage at 1 to 4°C.

8. The isolated platelets did not appear to be morphologically altered. The cell outline was regular and the size did not vary extremely.

9. Both methods are recommended for securing pure platelet suspensions. Such suspensions should prove to be very satisfactory for studies of the physiology, the chemical constitution, and the physical properties of the mammalian blood platelet.
IN VITRO STUDY OF BONE MARROW
Authors: PLUM CLAUS MUNK
Published: November 2019

Certain problems in erythrocytogenesis have been studied by means of the in vitro culture of bone marrow. A few conclusions have been reached by this method:

1. Liver extract stimulates production of mature erythrocytes.

2. Plasma contains substances which stimulate the production of mature erythrocytes.

3. Plasma in anemic individuals (anemia of bleeding) probably contains substances which stimulate the production of mature erythrocytes; and the greater the anemia, the greater the stimulation.

4. Mitoses do not account for the production of mature erythrocytes from erythroblasts. Erythropoiesis rather occurs in two stages, in the first of which mitosis is of prime importance, and in the second of which gemmation of erythroblasts is the main mechanism.
THE HISTOPATHOLOGY OF LESIONS IN THE BONE MARROW OF PATIENTS HAVING ACTIVE BRUCELLOSIS
Authors: SUNDBERG R. DOROTHY , SPINK WESLEY W.
Published: November 2019

1. Aspirated sternal bone marrow was studied in 9 patients with active brucellosis. Eight of the 9 patients had a demonstrable bacteremia due to Br. abortus.

2. Particles of marrow in 4 of the 9 patients revealed the presence of granulomatous lesions. In 1 case, the presence of a relatively large lesion permitted the study of the lesion in detail by means of serial sections. The alterations in the cellular pattern of the marrow and of the peripheral blood of the 9 patients were described.

3. The histopathology of the marrow in active brucellosis has been compared with the alterations in the other organs and tissues as reported in the literature. Comparisons have also been made between the granulomatous lesions in the marrow of brucellosis and those found in tuberculosis and sarcoidosis.

4. Aspirated sternal marrow for cultural and histological purposes merits further consideration as a diagnostic aid in active brucellosis.
A PHYSIOLOGICAL STUDY OF ERYTHROBLASTS IN THE DUCK
Authors: ROSTORFER H. H. , RIGDON R. H.
Published: November 2019

1. A method for the separation of erythroblasts in quantity from normal red cells in the blood of ducks infected with malaria has been described.

2. The erythroblasts in comparison to the normal adult red cells of the duck have a larger cell volume, less hemoglobin, and show a greater discrepancy between the colorimetric hemoglobin and hemoglobin calculated from the oxygen capacity.

3. The erythroblasts in the duck use four to five times the amount of oxygen that is consumed by the adult red cells in the ducks.

4. The function and possible fates of the erythroblasts which occur in the duck during the anemia caused by malaria are discussed.
Pre-pre-B acute lymphoblastic leukemia: high frequency of alternatively spliced ALL1-AF4 transcripts and absence of minimal residual disease during complete remission
Authors: Janssen JW , Ludwig WD , Borkhardt A , Spadinger U , Rieder H , Fonatsch C , Hossfeld DK , Harbott J , Schulz AS , Repp R
Published: November 2019

We used the polymerase chain reaction (PCR) to detect ALL1-AF4 rearrangements, the molecular hallmark of t(4;11) in a series of 46 pre- pre-B (CD19+, CD24+, CD10/CD20/cylgM/sIgM-) acute lymphoblastic leukemias (ALL). Eighteen patients (39%) exhibited fusion transcripts including 4 of 12 children and 14 of 34 adults. This genetic defect was associated with hyperleukocytosis (median leukocyte count 176 x 10(9)/L) and expression of myeloid-associated antigens (CDw65+). In contrast, only two patients from a group of 67 common (CD19/CD10+, cylgM/sIgM-) and pre-B ALLs (CD19/cylgM+, CD10 +/-, sIgM-) showed ALL1- AF4 mRNA. All PCR-positive cases showed multiple amplification products representing alternative splicing events. Moreover, reciprocal der (4)- derived AF4-ALL1 transcripts were observed in 65% of the cases analyzed. Eight of the 18 pre-pre-B ALL patients with an ALL1-AF4 recombination are currently in complete continuous remission for up to 54 months (median, 26 months). Twelve remission samples were available from seven cases, and all of them lacked evidence of minimal residual disease. Overall this study documents a similarly high incidence of ALL1-AF4 recombinations in children (infants excluded) and adults with pre-pre-B ALL and demonstrates the decline of the leukemic cell clone below the detection level of PCR in a remarkable proportion of patients under intense treatment protocols.
N- and O-glycosylation muteins of recombinant human erythropoietin secreted from BHK-21 cells
Authors: Fibi MR , Hermentin P , Pauly JU , Lauffer L , Zettlmeissl G
Published: November 2019

Single-site glycomuteins of recombinant human erythropoietin (rhuEpo) were constructed and transiently and stably expressed in BHK-21 cells. The transient expression levels varied among muteins, being highest for mutein rhuEpoGln24 followed by wild-type rhuEpo (rhuEpowt). All other glycomuteins, including rhuEpoGln38, rhuEpoGln83, rhuEpoThr126, and rhuEpoGly126, were secreted at lower levels than rhuEpowt. Muteins expressed in stable cell lines showed similar differences in expression levels. Also each mutein could be affinity-purified from culture supernatants, and was biologically active in vivo. Based on secretion rates from BHK-21 cells, the most potent erythropoietin was rhuEpoGln24. This mutein is also considered to have biologic activities that are superior to rhuEpowt.
Infection with Nippostrongylus brasiliensis induces invasion of mast cell precursors from peripheral blood to small intestine
Authors: Kasugai T , Tei H , Okada M , Hirota S , Morimoto M , Yamada M , Nakama A , Arizono N , Kitamura Y
Published: November 2019

Precursors of mast cells were defined as cells that formed mast-cell colonies in methylcellulose culture (CFU-mast). Mononuclear cells (MNC) were obtained from the bone marrow, peripheral blood, and small intestine of Ws/Ws rats with a small deletion at the tyrosine kinase domain of c-kit and of control normal (+/+) rats. In the culture containing concanavalin A-stimulated spleen cell conditioned medium (ConA-SCM) alone, the numbers of mast-cell colonies produced by Ws/Ws MNC were comparable with those of +/+ MNC. In the culture containing both ConA-SCM and stem cell factor (a ligand of c-kit), however, the numbers of mast-cell colonies produced by +/+ blood MNC were 107 times as great as that of Ws/Ws blood MNC. Using this culture condition, we investigated changes in concentration of CFU-mast in the marrow, blood, and intestine of +/+ rats after infection with Nippostrongylus brasiliensis (NB), which induced marked mast-cell accumulation in the small intestine. The concentration of CFU-mast in blood dropped to 21% of preinfection levels 1 week after the NB infection. In contrast, a sevenfold increase of CFU-mast occurred in the small intestine. The proportion of CFU-mast in S phase of the cell cycle remained at low levels in the marrow and blood after NB infection, but it increased significantly in the small intestine. The present result suggests that NB infection induces the invasion of CFU-mast into the intestine from blood and their subsequent proliferation in the tissue site.
Synergistic effects of thrombopoietin and granulocyte colony- stimulating factor on neutrophil recovery in myelosuppressed mice
Authors: Grossmann A , Lenox J , Deisher TA , Ren HP , Humes JM , Kaushansky K , Sprugel KH
Published: November 2019

Severe suppression of the hematopoietic system is a major factor in limiting chemotherapy dose escalation. To determine whether a combination of human recombinant granulocyte colony-stimulating factor (G-CSF) and thrombopoietin (TPO) would alter recovery of platelets, red blood cells (RBCs), or neutrophils after myeloablative therapy, myelosuppressed mice were treated with sc injections of TPO (90 micrograms/kg), G-CSF (250 micrograms/kg). TPO plus G-CSF or vehicle and complete blood counts were measured. Marrow and spleen cells were obtained at various times and assayed for erythroid, myeloid, and megakaryocytic progenitors. The prolonged neutropenia in vehicle controls (14 days) was significantly shortened in mice treated with G-CSF or TPO for 14 days. The combination of TPO plus G-CSF further reduced the duration of neutropenia. TPO and TPO plus G-CSF treatments also significantly shortened thrombocytopenia compared to vehicle. Recovery of RBCs was also enhanced in mice treated with either G-CSF or TPO, or the combination. Furthermore, treatment with G-CSF and/or TPO hastened myeloid, erythroid, and megakaryocyte progenitor recovery compared to vehicle controls. These results show that the combination of TPO plus G-CSF acts synergistically to accelerate neutrophil recovery in myelosuppressed mice and does not compromise the platelet or RBC response to TPO therapy.
Megakaryocytic cell line-specific hyperploidy by cytotoxic necrotizing factor bacterial toxins
Authors: Hudson KM , Denko NC , Schwab E , Oswald E , Weiss A , Lieberman MA
Published: November 2019

Cytotoxic necrotizing factor (CNF) toxins, isolated from certain Escherichia coli strains known to cause intestinal and extra intestinal infections, induce reorganization of the actin cytoskeleton and generate hyperploidy in adherent cell lines. We have examined the effect of CNF toxin on one of the few cell types that naturally increase nuclear DNA content, megakaryocytes. Our studies show that only hematopoietic cells capable of differentiating along the megakaryocyte lineage responded to the CNF2 toxin by becoming polyploid and by reorganizing actin. The K562, HEL, and CHRF-288–11 cell lines can be induced with phorbol ester to differentiate along the megakaryocyte lineage, and these cells also respond to the toxin with increased DNA content and actin cytoskeletal rearrangements. Interestingly, treatment of the K562 and HEL cell lines with CNF2 does not result in an increase in production of the megakaryocytic marker glycoprotein IIIa, unlike phorbol ester treatment. Conversely, two T-cell leukemic cell lines, CEM and Molt4, and the promyelocytic HL-60 cell line, which do not differentiate along the megakaryocyte lineage in response to phorbol myristate acetate, do not respond to CNF2, by increased expression of gpIIIa, increased nuclear DNA content, or actin reorganization. A potential target of these toxins, RhoA, is expressed by both megakaryocytic and nonmegakaryocytic cell lines, as shown by reverse transcription-polymerase chain reaction and Western blot. Although it is clear that the CNF toxins can affect a wide variety of adherent nonhematopoietic cell lines, we propose that the response to CNF, in terms of reorganizing actin structure and increase in DNA content in hematologic suspension cells, correlates with the capability of these target cells to differentiate along the megakaryocytic lineage.
Interaction between COX-1 and COX-2 increases susceptibility to ischemic stroke in a Chinese population
Authors: Zhao Lei , Fang Jinghuan , Zhou Muke , Zhou Jie , Yu Lihua , Chen Ning , He Li
Published: November 2019

Background

Mutations of cyclooxygenase gene (COX gene) may increase the susceptibility of ischemic stroke. We investigated five variants (rs5788, rs1330344, rs3842788, rs20417, and rs689466) of two COX genes in order to explaining the association between these polymorphisms and we also investigated the association between these variants and ischemic stroke risk to determine whether gene–gene interaction between these genes increases the susceptibility of ischemic stroke or its subtypes.

Methods

A total of 1981 study subjects (1078 cases and 903 control subjects) were recruited. The interaction of multiple factors was investigated using Multifactor Dimensionality Reduction. The additive effect of single nucleotide polymorphisms on ischemic stroke or its subtypes were analyzed by multiple factor logistic regression.

Results

At COX-1(rs1330344), AA genotype carriers had a lower susceptibility of ischemic stroke (OR = 0.657, 95%CI = 0.437–0.988, P = 0.044), and A allele carriers had a lower susceptibility of ischemic stroke (OR = 0.812, 95%CI = 0.657–0.978, P = 0.029). At COX-1(rs3842788), AA genotype carriers had a higher susceptibility of ischemic stroke (OR = 5.203, 95% CI = 1.519–5.159, P = 0.016). At COX-2 (rs689466), AA genotype carriers had a higher susceptibility of large-artery atherosclerosis (OR = 1.404, 95% CI = 1.019–1.934, P = 0.038). COX-1(rs1330344, rs3842788) and COX-2 rs689466 interacted in SVO, but had no additive effect with ischemic stroke and other subtypes.

Conclusions

At rs1330344, AA genotype may reduce the susceptibility of ischemic stroke. At rs3842788, AA genotype may increase the susceptibility of ischemic stroke. At rs689466, AA genotype may increase the susceptibility of large-artery atherosclerosis (LAA). COX − 1(rs1330344, rs3842788) and COX-2 rs689466 interacted in small vessel occlusion (SVO), but had no additive effect with ischemic stroke and other subtypes.
Determinants of breast cancer in Saudi women from Makkah region: a case-control study (breast cancer risk factors among Saudi women)
Authors: Alsolami Fatmah J. , Azzeh Firas S. , Ghafouri Khloud J. , Ghaith Mazen M. , Almaimani Riyad A. , Almasmoum Hussain A. , Abdulal Rwaa H. , Abdulaal Wesam H. , Jazar Abdelelah S. , Tashtoush Sufyan H.
Published: November 2019

Background

There are various factors that play a major role in influencing the overall health conditions of women diagnosed with breast cancer. The population of women in Makkah region are diverse, therefore it is significant to highlight the possible determinants of breast cancer in this population. This is a case-control study that assessed determinants of breast cancer including socioeconomic factors, health-related characteristics, menstrual histories and breastfeeding among postmenopausal women in Makkah region in Saudi Arabia.

Methods

A total of 432 female participants (214 cases and 218 controls) were recruited for this study. A validated questionnaire was completed by trained dietitians at King Abdullah Medical City Hospital in the Makkah region of Saudi Arabia.

Results

Results displayed that determinants of breast cancer were associated significantly (P < 0.05) with unemployment, large family size, lack of knowledge and awareness about breast cancer, obesity, sedentary lifestyle, smoking, starting menarche at an early age, as well as hormonal and non-hormonal contraceptive use. There was no effect of diabetes, hypertension, hyperlipidemia, and duration of breastfeeding on the incidence of breast cancer.

Conclusion

In summary, the results of this study accentuate the possible effect of socioeconomic factors, health-related characteristics and menstrual history on the incidence of breast cancer in postmenopausal women in the Makkah region. Education programs should be applied to increase breast cancer awareness and possibly decrease its incidence.
Spontaneous disappearance and recurrence of impending macular hole: a case report
Authors: Miyamoto Makiko , Shimizu Kazuhiro , Sato Yohei , Konose Bunsei , Mano Natsuko , Watanabe Hiroko , Ikeda Tsunehiko
Published: November 2019

Background

There have been several reports of spontaneous closure and reopening of a macular hole, however, in most of those cases, it was observed in eyes post vitrectomy. Here, we report a case of multiple episodes of spontaneous disappearance and recurrence of impending macular hole (stage 1B macular hole) with no history of previous surgery.

Case presentation

A 76-year-old Japanese man presented with a primary complaint of reduced visual acuity in his right eye. On initial examination, the visual acuity in his right and left eye was 0.4 and 0.01, respectively. He had previously been diagnosed as having macular degeneration of unknown origin in his left eye. Optical coherence tomography imaging confirmed vitreomacular traction and impending macular hole in his right eye. After a 1-week follow-up period, posterior vitreous detachment was detected, and the impending macular hole appeared to be resolved. Two months later, the impending macular hole had completely disappeared and his visual acuity had improved to 0.9. Six months later, he again noticed decreased vision in his right eye. An examination revealed that his visual acuity had dropped to 0.4, and there was a recurrence of impending macular hole. An optical coherence tomography examination showed no definitive findings of vitreous traction, and, 1 month later, spontaneous disappearance was observed again and his visual acuity improved to 0.7.

Conclusions

In this case, both the initial onset and the recurrence involved impending macular hole, however, the optical coherence tomography findings differed at each examination. These findings suggest that some causes other than vitreous traction were responsible for both the spontaneous disappearance and recurrence of the impending macular hole in this present case.
Preliminary report of a novel formulation of clinical-grade, fully matured, tumor-associated peptide-loaded dendritic cells for cancer immunotherapy
Authors: Mirandola Leonardo , Chiriva-Internati Maurizio , Bresalier Robert , Marincola Francesco M. , Figueroa Jose A. , Dahlbeck Scott
Published: November 2019

Background

We developed and clinically test a new method to manufacture mature dendritic cells for autologous cell therapy of solid and hematological malignancies.

Methods

Peripheral blood monocytes are matured into dendritic cells with GM-CSF/IL-4 mixture, and then activated through IL1b, TNFa, IFNa-2A, and Poly(I:C), then viably frozen until use. DC are injected intra-dermally for a total of 6 injections.

Results

High-grade mDC with high pre- and post- freezing yields could be generated. These DC spontaneously produce IL12p70 and they can be further stimulated via CD40. In a patient with advanced pancreatic cancer treated with our mDC formulation, we observed no toxicity but remarkable immune response and objective response in terms of tumor shrinking.

Conclusion

We describe a new method to manufacture GMP-grade dendritic cells for autologous therapeutic cancer vaccines. We also show proof-of-principle efficacy in a patient with advanced pancreatic cancer.

Trial registration

NCT02705703.
Loss of Corneal Reflex in Children Undergoing Spinal Anesthesia: A Case Series
Authors: Holman Ashlee E. , Puglia Michael P.
Published: November 2019

Spinal anesthesia is administered for select procedures in the pediatric population and offers a safe alternative to general anesthesia. In this case series, we report loss of corneal and eyelash reflexes in 4 children who underwent spinal anesthesia for lower abdominal procedures. While initially thought to be the result of higher-than-intended spinal anesthesia, the observation that gentle stimulation produced vigorous phonation, orbicularis oculi constriction, and upper extremity movement suggests an alternative mechanism. This finding highlights a potential gap in knowledge related to the effect spinal anesthesia has on brain dynamics in children.
A Novel Approach to Postoperative Ear Pain—Greater Auricular Nerve Block Catheter: A Case Report
Authors: Ellison Matthew B. , Howell Stephen , Heiraty Payam , Wilson Colin , Shepherd Jason , Ellison Pavithra R.
Published: November 2019

A 70-year-old man presented for repair of an ear avulsion injury sustained from an all-terrain vehicle accident. A continuous technique using a catheter for a greater auricular nerve (GAN) block was performed in the preoperative area followed by general anesthesia in the operating room. No opioids were administered during the surgical procedure or in the immediate postoperative period. The GAN catheter was kept in place for 3 days with near-complete pain relief per the patient. To our knowledge, there are no case reports that describe a continuous GAN technique for surgery and postoperative pain.
THE INFLUENCE OF THE FOAMING AGENTS NATURE ON PHYSICAL AND TECHNICAL PROPERTIES OF FOAM
Authors: Попов Александр , Popov Aleksandr , Нелюбова В.В. , Nelyubova Viktoriya , Нецвет Д. , Necvet Dar'ya
Published: November 2019

The paper considers the influence of the nature of foaming agent on the properties of foams. Based on the analysis of the market of modern pore-forming additives, from the number of foaming agents the most widely used components, as well as novelties of the market, have been chosen. The technical characteristics of the foaming agents provided on the market are reviewed. The influence of foaming agent concentration, composition and base on the foam expansion, stability and density of foams is studied in the paper. The optimum ("working") concentrations of foaming additives are determined taking into account their stability. The stability of foams formed on the basis of working solutions in porous systems of various compositions is studied. Based on the complex of studies, the protein foaming agents are ranked according to the degree of their effectiveness, according to the data on the physical and technical properties of foams obtained on their basis.
STATISTICAL SIGNIFICANCE OF PREDICTING THE PRODUCTION PROCESS RESULTS BY MEANS OF AN ARTIFICIAL NEURAL NETWORK
Authors: Макаров Александр , Makarov Aleksandr
Published: November 2019

As a result of the research of production process organization for the roof construction of residential multi-storey buildings, an artificial neural network (ANN) was designed, the purpose of which is to predict the labor productivity based on organizational factors. One of the main tasks on the way to this purpose is the training of ANN on precedents of the sample extracted from the research object. In view of the deficiency of training data, the main problem is to determine the conditions for the statistical significance of the predictions of the model trained on limited sample. This article is devoted to solving this problem within the research of production organization. The paper uses the provisions of the statistical learning theory, the notion of the Vapnik-Chervonenkis dimension for describing the sample complexity, and also the approaches of probably approximately correct learning (PAC-learning). The technologies of statistical bootstrapping and bagging are described, which allow expanding the training sample. ANN training is conducted using a computer experiment on the programming language Python. The bounds of the theoretical sample complexity, which is necessary for obtaining of ANN results within a given confidence interval with a confidence level of 0,95, were estimated. The sample was transformed by an order comparable to the theoretical lower bound. ANN was trained and the mean square error (MSE) in the test sample was defined, which amounted to . The theoretical bounds of the sample complexity to ensure a given statistical significance are determined in the article. After the ANN training on the sample, the order of which corresponds to theoretical lower bound, a prediction error was obtained on the test sample within the given confidence interval.