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A consensus mechanism must be cared for protecting blockchain against attacks
yoshiyasu takefuji

yoshiyasu takefuji

October 23, 2020
Telenti A. et al. wrote a perspective on treating medical data as a durable asset using blockchain and AI technology1. In order to use the blockchain technology, detection and protection mechanisms against attacks must be embedded in blockchain applications for protecting vulnerabilities of known consensus algorithms.
Long- and short-read metabarcoding technologies reveal similar spatio-temporal struct...
Brendan Furneaux
Mohammad Bahram

Brendan Furneaux

and 4 more

October 22, 2020
Fungi form diverse communities and play essential roles in many terrestrial ecosystems, yet there are methodological challenges in taxonomic and phylogenetic placement of fungi from environmental sequences. To address such challenges we investigated spatio-temporal structure of a fungal community using soil metabarcoding with four different sequencing strategies: short amplicon sequencing of the ITS2 region (300–400\ bp) with Illumina MiSeq, Ion Torrent Ion S5, and PacBio RS II, all from the same PCR library, as well as long amplicon sequencing of the full ITS and partial LSU regions (1200–1600\ bp) with PacBio RS II. Resulting community structure and diversity depended more on statistical method than sequencing technology. The use of long-amplicon sequencing enables construction of a phylogenetic tree from metabarcoding reads, which facilitates taxonomic identification of sequences. However, long reads present issues for denoising algorithms in diverse communities. We present a solution that splits the reads into shorter homologous regions prior to denoising, and then reconstructs the full denoised reads. In the choice between short and long amplicons, we suggest a hybrid approach using short amplicons for sampling breadth and depth, and long amplicons to characterize the local species pool for improved identification and phylogenetic analyses.
Analysis of circulating nutritional antigen-specific T-cells in celiac disease and in...
Rainer Glauben
Yasmina Rodriguez-Sillke

Rainer Glauben

and 6 more

October 22, 2020
Background: The present study aims to detect, quantify and analyze circulating nutritional antigen-specific T-cells in patients with celiac disease (CeD) as well as inflammatory bowel disease (IBD), thus comparing the specific T-cell response following barrier disruption and antigen translocation. Methods: The antigen-reactive T-cell enrichment (ARTE) technique was applied allowing for a phenotypical and functional flow cytometric analysis of rare nutritional antigen-specific T-cells, including the CeD-causing gliadin (gluten), in the peripheral blood. Results: Our study indicates that by applying the ARTE technique, differences of gluten-specific T-cells as well as the differential cytokine expression between the patient groups can be detected, even without the burdening gluten re-exposure of the patients. CeD patients, independent from the presence or absence of gluten exposure in their current diet, featured an increase of the frequency of gliadin-specific T-cells, which were characterized by a pro-inflammatory phenotype. However, only for active CeD and a consecutive small intestinal barrier breach, an increase of distinct nutritional T-cells could be detected. Accordingly, frequency as well as pro-inflammatory phenotype of nutritional antigen-specific T cells were highest in Crohn’s disease patients with small intestinal inflammation whereas no significant increase was observed in ulcerative colitis. Conclusion: In summary, the ARTE method allows not only for detection but also for functional analysis of these rare cells even in healthy subjects. Applying this method, we were able to demonstrate that for non-CeD-related nutritional antigens, small intestinal barrier breach is mandatory for a peripheral antigen-specific T-cell.
Asymptomatic infection outcomes for brucellosis: A meta-analysis
Huixin Yang
Xiangyi Zhang

Huixin Yang

and 9 more

October 22, 2020
Abstract Background A Brucella leak occurred at the Lanzhou Biopharmaceutical Factory in China. As of September 14, 2020, 96 brucella asymptomatic infections have been detected, while little is known about them due to lack of the follow-up study. Methods To synthesise the evidence of the effectiveness of asymptomatic brucellosis infection. Multiple databases Were searched and inclusion Criteria included participants were newly infected with Brucella, and had a positive serum agglutination test (SAT≥100),no symptoms, such as fever, sweating, malaise; Papers were quality assessed used the Cochrane risk bias tool. Results Meta-analyses were performed for risk difference and standardised mean difference of all asymptomatic brucellosis infection. we conducted a meta-analysis of the published literatures. A total of 56 asymptomatic infections were included in, male adults accounted for the majority of the cases, and both occupational and non-occupational groups had asymptomatic infection; 20%(95%CI:0%-55%) of subjects had positive outcomes and the follow up time ranged from 1-12 months in meta-analysis. Conclusions Meta-analysis suggests that both occupational and non-occupational groups have asymptomatic infection and male adults account for the majority and most of the subjects showing positive outcome exposed to sheep or unpasteurized dairy products. Key words: Brucellosis, asymptomatic infection, meta-analysis
Do wild suids from Ndumo Game Reserve, South Africa, play a role in the maintenance a...
Cynthia Mapendere
Ferran Jori

Cynthia Mapendere

and 3 more

October 22, 2020
In Southern Africa, the African Swine Fever (ASF) sylvatic cycle presents a permanent threat for the development of the pig farming industry. Warthogs (Phacochoerus africanus) and bushpigs (Potamochoerus larvatus), wild reservoirs of ASF are present in Ndumo Game Reserve (NGR), located in Northern KwaZulu Natal Province in South Africa and within 30 km of the locations of endemic ASF outbreaks in Mozambique where sylvatic disease transmission has been implicated. To assess if wild suids represent a risk of ASF virus spillover to domestic pigs in the neighbouring community, transect counts and fence patrols were conducted and camera traps were deployed in NGR to estimate wild suid abundance and incursions outside NGR boundaries. We searched for Ornithodoros ticks in 35 warthog burrows distributed across different NGR areas. Pig farmers (n=254) surrounding Mathenjwa Community were interviewed to gather information on interactions between domestic and wild suids and the occurrence of ASF. We conclude that NGR has established populations of bushpigs and warthogs, estimated at 5 and 3-5 individuals/km2 respectively. Both species move out of the reserve regularly (15.4 warthogs/day and 6.35 bushpigs/day), with a significant increase of movements during the dry season. Some farmers observed warthogs and bushpigs as far as 8 and 19 km from the reserve respectively, but no direct wild-domestic suids interactions nor any ASF outbreaks were reported. In addition, no soft ticks were found among the 35 warthog burrows. The absence of ticks in warthog burrows from NGR and the absence of reported outbreaks and familiarity with ASF in the surrounding farming area, suggest that a sylvatic cycle of ASF is at present unlikely in NGR. However, further research should be undertaken to confirm this by surveying a larger number of warthog burrows and monitoring potential antibodies in warthogs from NGR and domestic pigs in the neighbouring community.
Fatigue fracture assessment of 10CrNi3MoV welded load-carrying cruciform joints consi...
Song Wei
LIU SONG

Song Wei

and 7 more

October 22, 2020
Fatigue experiments and numerical simulations based on the Linear Elastic Fracture Mechanics (LEFM) theory were conducted on the Even-Matched (EM) and Under-Matched (UM) 10CrNi3MoV Load-carrying Cruciform Welded Joints (LCWJs). The study firstly experimentally investigated the Fatigue Crack Growth Rate (FCGR) of base metal, EM, and UM weldments. The corresponding Paris parameters as essential input data are provided to assess the fatigue crack propagation behavior for weld toe and weld root failure of LCWJs. On the one hand, the Stress Intensity Factors (SIFs) at weld toe and weld root were calculated considering the effects of LCWJ specimen geometries, initial crack types, and sizes. The comparisons between simulated results and standards analytical solutions were executed, which exhibit good accordance. It proved that the fatigue fracture simulation procedure based on LEFM is appropriate for the fatigue assessment of LCWJs. Eventually, it conducted the parametric analysis by predicted S-N curves, which included in the weld length, initial crack shape, initial crack size, penetration length, and materials fracture parameter, to explore some safety assessment reference lines for both failure modes of LCWJ.
Kejimkujik Calibrated Catchments: a benchmark dataset for long-term impacts of terres...
Shannon Sterling
Tom Clair

Shannon Sterling

and 5 more

October 22, 2020
Delays in forest recovery from terrestrial acidification combined with climate change is leading Acadian Forest ecosystems into new territory. Kejimkujik Calibrated Catchments (KCC) Study Program was established in an around Kejimkujik National Park and Historic Site (KNPHS) in Southwest Nova Scotia (SWNS) in the late 1970s to increase our understanding of the impacts of acid precipitation on relatively pristine ecosystems. KCC now have one of the longest continuously monitored water chemistry records in North America, with data collection beginning in 1980. Its infrastructure includes three gauged streams, twelve forest inventory plots, an atmospheric deposition monitoring station, and three streams with continuous water quality monitoring and regular lab analysis of stream chemistry, and recent LiDAR coverage. The KCC fits into a wider network of monitored lakes. Data collected at the KCC form a key datapoint in comparisons of catchment response to terrestrial acidification in the context of a warming climate, due to their high and increasing DOC levels, highly dilute waters, lowland topography and extensive wetlands. KCC are also emerging as an important source of information for species at risk protection as SWNS was declared one of the 11 national priority places for biodiversity protection.
Stream temperature response to 50% strip-thinning in a temperate forested headwater c...
Dinh Oanh
Takashi Gomi

Dinh Oanh

and 6 more

October 22, 2020
We examined stream temperature response to 50% strip-thinning of a 20- to 50-year-old Japanese cedar and cypress plantation in a 17-ha headwater catchment. The thinning lines extended through the riparian zone. Paired-catchment analysis was applied to estimate changes in daily maximum, mean, and minimum stream temperatures for the first year following treatment. Significant effects on daily maximum stream temperature were found for April to August, ranging from 0.6 to 3.9 °C, similar to the magnitude of effect found in previous studies involving 50% random thinning. Multiple regression analysis revealed that treatment effects for maximum daily stream temperature were positively related to solar radiation and negatively related to discharge. Frequent precipitation during the summer monsoon season produced moderate increases in discharge (from 1 to 5 mm day-1), which mitigates stream temperature increases associated with solar radiation. Catchment hydrologic response to rain events can play an important role in controlling stream thermal response to forest management practices.
Thyroid storm after mitral valve repair in a patient with Becker muscular dystrophy
Kazuhiro Yamazaki
Kenji Minakata

Kazuhiro Yamazaki

and 5 more

October 22, 2020
A 40-year-old male with Becker muscular dystrophy presented with severe mitral regurgitation and underwent mitral valve repair. Following the surgery, the patient became tachycardic, and developed a continuous high grade-fever and hyperbilirubinemia. The patient's condition worsened and we eventually tested his thyroid levels and discovered abnormally high thyroid levels. After diagnosing a severe thyroid storm, the patient was treated with oral administration of Lugol's iodine and thiamazole, as well as an intravenous steroid, which led to an immediate improvement of symptoms. The incidence of thyroid storm after open-heart surgery is extremely rare but highly life-threatening if unrecognized.
Dynamic epigenome changes in response to light in Brachypodium distachyon
yunyun An
Wei Shen

yunyun An

and 4 more

October 22, 2020
Light plays an important role in many plant biological processes such as photosynthesis and photomorphogenesis. In this study, we applied RNA-seq, ATAC-seq and ChIP-seq to study transcriptional regulation at multiple levels in Brachypodium distachyon (B. distachyon) under controlled light and extended darkness conditions. We have identified 8,400 differentially expressed genes (DEGs), and they are enriched in photosynthesis Gene Ontology terms. ATAC-seq signal decreased after extended darkness, indicating that light has a genome-wide impact on chromatin accessibility. We also found that differential H3K4me3 and H3K9ac modifications are enriched in gene loci associated with photosynthesis and other light-dependent reactions. Finally, ChIP-seq revealed that a HY5-Like transcription factor could directly bind to the promoter open chromatin regions of these light reaction genes. Taken together, our results indicated the dynamic transcriptional reprograming associated with light-dark changes in Brachypodium could be resulted from the combinatorial action of multiple epigenetic features.
Remedial dosing regimens for delayed or missed rivaroxaban doses in patients with non...
Xiaoqin Liu
Yiwei Yin

Xiaoqin Liu

and 5 more

October 22, 2020
Background: Rivaroxaban is an oral anticoagulant used widely for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). During long-term anticoagulant therapy, delayed or missed doses are common. However, a lack of practical instructions on remedial methods has created a barrier to maximise the benefit of the medications. This study aimed to explore appropriate remedial dosing regimens for non-adherent rivaroxaban-treated patients. Methods: Monte Carlo simulation based on a previously established rivaroxaban population pharmacokinetic/pharmacodynamic (PK/PD) model for patients with NVAF was employed to design remedial dosing regimens. The proposed regimens were compared with remedial strategies in the European Heart Rhythm Association (EHRA) guide by assessing deviation time in terms of drug concentration, factor Xa activity, and prothrombin time under various scenarios of non-adherence. Results: The proposed remedial dosing regimens were dependent on delay duration. The missed dose should be taken immediately when the delay does not exceed 6 h; a half dose is advisable when the delay is between 6-20 h. A missed dose should be skipped if less than 4 h remains before the next dose. Age or renal function does not significantly influence remedial dosing regimens. The proposed regimens resulted in shorter deviation time than that of the EHRA guide in most non-adherence scenarios. Conclusion: EHRA guide may not provide optimal remedial strategies for rivaroxaban-treated non-adherent patients based on simulation. PK/PD and simulation provide valid evidence on the remedial dosing regimen of rivaroxaban for patients with NVAF, which could help to minimise the risk of bleeding and thromboembolism.
Maternal and child health handbook to improve continuum of maternal and child care in...
Ruoyan Gai Tobe
Syed Emdadul  Haque

Ruoyan Gai Tobe

and 5 more

October 22, 2020
Objective: This study aimed to evaluate the effectiveness of maternal and child health handbook (MCH) enhanced by mobile tools and to generate evidence informing the adoption of the program in Bangladesh Design: Cluster randomized controlled trial Setting: Two Upazilas in Bangladesh Population or Sample: Pregnant women Methods: Unions of the study settings were randomly allocated in either one of three groups: (1) Intervention 1 using both mobile platform and MCH, (2) Intervention 2 using MCH alone, or (3) the Control. A total of 3,002 participants were recruited. The interventions were designed to promote two-way communications between pregnant women/their families and community health workers by an empowering approach. Main outcome measures: continuum of care (CoC), neonatal mortality and morbidities Results: The interventions both significantly improved the utilization of CoC, although the overall proportion of CoC was relevantly low: 2.79% in the Control (95% CI: 1.37-3.54%), 6.16% in Intervention 2 (95% CI: 4.67-7.86%), and 7.89% in Intervention 1 (95% CI: 6.29-9.90%). Neonatal mortality rate with and without CoC was 5.43 per 1,000 (95% CI: 3.63 - 9.57 per 1,000) and 34.8 per 1,000 (95% CI: 24.3 - 45.4 per 1,000), respectively. Conclusion: our study indicated the effectiveness of the interventions by leveraging MCH and a mobile platform to promote uptake of CoC throughout prepartum, intrapartum and postpartum/neonatal periods, potentially bringing long-lasting benefits to mothers and their offspring. The explicit approach is expected to guide policy makers to adopt MCH interventions in primary healthcare strengthening at the community level.
Study on perinatal related factors of maternity and newborn in parturients with intra...
Yuru Fan
Chong Fan

Yuru Fan

and 10 more

October 22, 2020
Objective To investigate the impact of intrapartum fever on maternity and fetus. Design Retrospective cohort study. Setting Women’s Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China Population We studied intrapartum fever, as well as non-fever parturients, between January 1, 2018 and December 31, 2018. Methods We collected pregnancy outcomes of intrapartum fever and non-fever mother and neonatal data. Main outcomes and measures The obstetrics outcomes, complete blood cell count (CBC) and thereby converted neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR), as well as vaginal secretion were observed in women with and without intrapartum fever. Results Prepartum white blood cell (WBC), red blood cell (RBC), and hemoglobin (Hb) were all higher in febrile group, and WBC still higher but RBC and Hb lower after birth. Postpartum NLR and MLR were all higher in fever group but not preferred overtly difference before delivery. Additionally, the comparison of WBC, RBC, Hb, platelets (PLT), neutrophils, and monocytes in prepartum and postpartum all showed significant difference. Conclusions The differences of the prepartum WBC, RBC, Hb, and monocytes existed in the intrapartum fever and afebrile groups. Besides, the parturition could bring about the change of the value of CBC and intrapartum fever might aggravate or alleviate this change. Additionally, the intrapartum fever might not be caused mainly by infection and the difference between bacteria and fungus could reflect in the CBC. Keywords: Intrapartum fever, perinatal period, vaginal discharge examination
Associations between C-section and hand grip strength: an observational analysis and...
Xiaomeng Chu
Li Liu

Xiaomeng Chu

and 16 more

October 22, 2020
Objective: Hand grip strength (HGS) could be taken as a biomarker for overall health of individual. While growing evidence suggests cesarean section (C-section) related to child health, few studies have assessed its effect on the overall health status of offspring. Design: Cross-sectional cohort study. Setting: UK Biobank cohort. Population: A population-based cohort consisting of 160,635 participants for left HGS and 160,651 for right HGS aged between 40 and 69. Methods: Regression analyses were conducted to test the associations between C-section and left HGS and right HGS. Then, genome-wide of environment interaction study (GWEIS) was conducted by PLINK 2.0 to identify loci with gene-environment (G×E) interaction effects, using C-section as an environmental factor. FUMA platform was used for functional gene set enrichment analysis of identified candidate genes. Main Outcome Measures: C-sections and hand grip strength. Results: The regression analyses showed significant associations (P <0.001) between C-section and left and right HGS. GWEIS detected 6 significant G×E interaction effects on left HGS, such as ADGRV1 gene, POLR3G gene, and WASL gene. 32 significant G×E interactions effects on right HGS were detected, such as APBB2 gene, and CRPPA gene. Comparing the analyses results of left HGS and right HGS, identified suggestive significant interactions between CLEC16A gene and C-section, such as rs80001954 (Pright = 5.21 × 10−8, Pleft = 1.22 × 10−7); rs117658390 (Pright = 5.43 × 10−8, Pleft = 1.09 × 10−7) and rs79479146 (Pright  = 5.45 × 10−8, Pleft  = 1.22 × 10−7). Gene set enrichment analyses reported 12 GO terms, such as GO_CENTRAL_NERVOUS_SYSTEM_DEVELOPMENT (adjusted P = 1.98 × 10−3), and GO_HEAD_DEVELOPMENT (adjusted P = 5.09 × 10−3). Conclusion: Our study holds potential for clarifying the functional relevance of C-section with HGS
Mortality in Sickle Cell Disease -- A Population Based Study in an Aboriginal Communi...
VEENA SHESHADRI
Shabeer PK

VEENA SHESHADRI

and 5 more

October 22, 2020
Background: Sickle cell disease (SCD), the commonest monogenic disorder, affects more than 300,000 births annually, with 44,000 in India. While the clinical phenotype of SCD is considered to be milder in aboriginal populations in India, there is a paucity of data on outcomes. To determine the severity of SCD in this population, we studied mortality rates and causes of mortality in a longitudinal cohort of patients with SCD in a remote aboriginal community in India receiving community-based comprehensive care. Procedures: Causes of death in this cohort from January 2008 to December 2018 were analyzed. Details were collected from hospital records and in case of deaths at home, by utilizing the WHO verbal autopsy questionnaire. Results: The cohort consisted of 157 patients belonging to the Paniya, Betta Kurumba, Kattunyakan, and Mullu Kurumba tribes. During the study period, there were 22 deaths, all from the Paniya tribe. Twelve deaths (54.5%) occurred in the hospital and the remaining at home (45.5%) reflecting a crude mortality rate of 140 per 1000 population. 25% of deaths occurred in the 6-18 age group. There were no deaths in the 0-5 age group. The median age of death was 25 years, which was 20 years less than in the non-SCD aboriginal population. The leading causes of death were acute chest syndrome, anemia, and sepsis among the SCD patients and stroke and suicides in the non-SCD aboriginal population Conclusion: SCD is a severe disease among the Gudalur Valley’s aboriginal population with a significant risk of premature mortality.
Biomanufacturing of Value-Added Products from Oils or Fats: A Case Study of Yarrowia...
Na Liu
Ya-Hue Soong

Na Liu

and 6 more

October 22, 2020
The United States produces more than 10 million tons of waste oils and fats each year. This paper aims to establish a new biomanufacturing platform that convert waste oils or fats into a series of value-added products. Our research employs the oleaginous yeast Yarrowia lipolytica as a case study for citrate production from waste oils. First, we conducted the CFD simulation of the bioreactor system and identified that the extracellular mixing and mass transfer is the first limiting factor of an oil fermentation process due to the insolubility of oil in water. Based on the CFD simulation results, bioreactor design and operating conditions were optimized and successfully enhanced oil uptake and bioconversion in fed-batch fermentation experiments. After that, we investigated the impacts of cell morphology on oil uptake, intracellular lipid accumulation, and citrate formation by overexpressing and deleting the MHY1 gene in the wild type Y. lipolytica. Fairly good correlations were achieved between cell morphology and productivities of biomass, lipid, and citrate. Finally, fermentation kinetics with both glucose and oil substrates were compared and the oil fermentation process was carefully evaluated. Our research results suggest that waste oils or fats can be economical feedstocks for biomanufacturing of many high-value products.
Risk factors for complications of implantable venous access port usage among young pe...
Shanshan Qiu
Ming Hu

Shanshan Qiu

and 5 more

October 22, 2020
Background and Objectives: This study aimed to evaluate the utilization of totally implantable venous access ports (TIVAPs) and identify risk factors for complications associated with their usage in young pediatric patients with a solid tumor. Methods: We retrospectively investigated the clinical characteristics and procedure records of all patients admitted with a solid tumor who underwent TIVAP implantation and removal as well as line patency maintenance in our clinic from 2016 to 2019 at the Shanghai Children’s Medical Center. Results: Overall, 144 patients were evaluated over 28,444 catheter days. There was a greater risk of central line-associated bloodstream infection (CLABSI) in patients with neuroblastoma who were older in age and whose body mass index was lower. The rate of CLABSI was relatively increased in high-risk than low-risk and intermediate-risk neuroblastoma according to the Children’s Oncology Group (COG) classification system. There were no significant differences in complications between the TIVAP implantation group and the combined surgery group. Conclusions: Older age, lower BMI, and high COG risk are great risk factors of CLABSI in patients with neuroblastoma, thus requiring vigilant surveillance. Combining TIVAP insertion with biopsy and/or resection surgery should be given due consideration.
Donor characteristics and intra-operative total nucleated cell count influence hemato...
Jacob Kalin
Anh Thy Nguyen

Jacob Kalin

and 2 more

October 22, 2020
Background: Bone marrow graft cell content impacts engraftment potential after allogeneic hematopoietic cell transplantation (alloHCT). Surrogates such as intra-operative total nucleated cell count (ioTNC), are of unclear utility in predicting final graft characteristics. In addition, demographic and clinical factors may influence graft cellular profile and recipient engraftment. Procedure: We retrospectively reviewed marrow harvests at our institution performed between 2009 and 2019. During this time, an ioTNC was measured after 50% of the projected final graft volume was collected. Regression models were used to assess associations between ioTNC (cells/µL) and final graft CD34+ cells/mL, and between graft and donor characteristics and final graft CD34+ cells/mL. Results: Fifty-three marrow harvests and donor-recipient pairs were analyzed. Median (range) donor and recipient ages were 13 (0.7-28) years and 9 (0.2-21) years, respectively. The median ratio of donor/recipient weight was 1.225 (range 0.31-7.13). Median total volume of harvested marrow was 15.3ml/kg (range 4.3-20.4ml/kg) of donor weight and 19.4ml/kg (range 4.7-87.4ml/kg) of recipient weight. Median ioTNC was 20930/µL (range 6600-44310/ µL) or 2.1x109/mL, corresponding to median predicted final graft TNC of 3.59 x108/kg recipient weight (range 1.28-19.42x108). Simple linear regression between ioTNC and CD34+ cells/mL resulted in an R2 of 0.42. LASSO regression produced a moderately predictive model consisting of ioTNC, donor age, and donor weight (adjusted R2=0.7) of final graft CD34+ cells/mL. Conclusions: ioTNC and certain donor characteristic correlate moderately well with marrow product CD34+ cells/m, potentially informing donor selection and marrow procurement strategies.
Palifermin as Primary Prophylaxis for Mucositis Prevention in Patients with B-Cell No...
Anthony Zembillas
Stefanie Thomas

Anthony Zembillas

and 4 more

October 22, 2020
Palifermin as Primary Prophylaxis for Mucositis Prevention in Patients with B-Cell Non-Hodgkin LymphomaAnthony S. Zembillas, PharmD, BCPS, BCOP1,3, Stefanie M. Thomas, MD, MS2, Seth J. Rotz MD2, Ilia N. Buhtoiarov, MD2, Rabi Hanna, MD2(1) Pharmacy, Cleveland Clinic, Cleveland, OH;(2) Department of Pediatric Hematology Oncology and Bone Marrow Transplantation, Cleveland Clinic Children’s, Cleveland, OH;(3) Address correspondence to:Funding Source: Supported in part by a grant from the NIH NCATS (2KL2TR002547 PI Dweik, to S.J.R.)To the Editor:Progress continues to be made regarding the treatment of children and adolescents with aggressive B-cell Non-Hodgkin Lymphoma (NHL). Recent data demonstrated patients with mature B-cell NHL have an improved overall survival with the addition of rituximab to lymphomes malins B (LMB) chemotherapy.1 However, these patients experienced significant therapy-related adverse events including febrile neutropenia, stomatitis, and infection. Oral mucositis, the second most common adverse event, occurred in up to 80% of patients with grade 3 oral mucositis occurring in 71% of patients. 1Complications related to mucositis include significant morbidities such as severe pain requiring opioids, nutritional deficiencies necessitating parenteral nutrition, life-threatening bloodstream infections, and prolonged hospitalizations likely increasing the overall cost of care.2 Proper oral care is the standard first-line approach to mucositis prevention but its benefits may be limited with more intensive chemotherapy regimens.Palifermin, a human recombinant keratinocyte growth factor, is a preventative medication that has shown positive effects on reducing mucositis frequqncy and severity in children receiving cancer therapy.3 Studies of palifermin most frequently involve patient’s undergoing hematopoietic stem cell transplant (HSCT) with limited data in the non-HSCT setting.4-6 Data are encouraging regarding the use of palifermin as secondary prophylaxis, showing effectiveness in children and adolescents with NHL who previously developed mucositis.6 This data, combined with our experience of significant toxicity in our patient population led us to administer palifermin as primary prophylaxis for mucositis prevention in patients receiving Group B or Group C LMB therapy for B-cell NHL, as part of routine clinical practice.We first utilized this approach in a young adult male with Stage II A diffuse large B cell lymphoma (DLBCL) treated per Group B of ANHL1131. He received a single dose of palifermin 180 mcg/kg IV in the outpatient setting approximately three days prior to cycles 1 and 2. He did not receive palifermin prior to cycle 3 due to the perceived lower risk of mucositis. But after developing severe mucositis requiring opioid analgesics during cycle 3, palifermin was reinstituted prior to cycle 4. Of the three cycles where palifermin was used, there were no mucositis-related complications. The patient remains in complete remission one year post-therapy. The second patient was a young adult female with Burkitt lymphoma treated per Group C1 of ANHL1131. She received a single dose of palifermin 180 mcg/kg IV in the outpatient setting approximately 3 days prior to all 6 cycles of chemotherapy. She did not have mucositis-related complications or require opioids for mucositis-related pain throughout her entire treatment. She has no evidence of disease at end of therapy. No toxicities from palifermin were noted in either patient.Our experience suggests that palifermin is a potential therapeutic option as primary prophylaxis for NHL patients receiving high intensity chemotherapy commonly causing grade 3-4 mucositis. Prospective studies are warranted to confirm the benefit and safety of palifermin compared to other interventions such as oral saline rinses or a standardized oral mouth care protocol.ReferencesMinard-Colin V, Auperin A, Pillon M, Burke GAA, Barkauskas DA, Wheatley K. Rituximab for high-risk, mature B-cell non-Hodgkin’s lymphoma in children. N Engl J Med 2020;382:2207-2219.Spielberger R, Stiff P, Bensinger W, Gentile T, Weisdorf D, Kewalramani T. Palifermin for Oral Mucositis after Intensive Therapy for Hematologic Cancers. N Engl J Med2004;351:2590-2598.Mazhari, F, Shirazi AS, Shabzendehdar M. Management of oral mucositis in pediatric patients receiving cancer therapy: a systematic review and meta-analysis. Pediatr Blood Cancer 2019;66:e27403.Vadhan-Raj S, Trent J, Patel S, Zhou X, Johnson MM, Araujo D. Single-dose palifermin prevents severe oral mucositis during multicycle chemotherapy in patients with cancer. Ann Intern Med 2010;153:358-367.Saber W, Zhang MJ, Steinert P, Chen Min, Horowitz MM. The impact of palifermin use on hematopoietic cell transplant outcomes in children. Biol Blood Marrow Transplant 2016;22:1460-1466.Dazhi L, Seyboth B, Mathew S, Gilheeney SW, Chou AJ, Drill E. Retrospective evaluation of palifermin use in nonhematopoietic stem cell transplant pediatric patients. J Pediatr Hematol Oncol 2017;39:177-182.
#Bibliotheca 001: Geometri
Matematik ve Matematik Mühendisliği Topluluğu

Matematik ve Matematik Mühendisliği Topluluğu

November 12, 2020
    Mustafa Kemal Atatürk'ün geometri öğrenmeyi kolaylaştırmak amacıyla Osmanlıca geometri terimlerini Türkçe'ye çevirdiğini ve çalışmalarını "Geometri" adıyla bir kitapta toplayarak yayınladığını biliyor muydunuz?
The Diagnostic Evaluation of Clinical Symptoms and Signs for COVID¬-19 in hospitalize...
Hossein  Hatami
Mohammad  Saeidi

Hossein Hatami

and 3 more

October 22, 2020
Background: A novel coronavirus, led to a rapidly spreading outbreak of COVID¬19 which caused morbidity and mortality worldwide. Appropriate case definitions can help in diagnosing COVID¬19. The aim of this study was to evaluate the existing and potential syndromic case definitions of COVID¬19 using latent class analyses (LCA) among hospitalized patients of North Iran. Methods. The data of this cross-sectional study was collected from hospitalized patients tested for COVID-¬19 by RT-PCR between February 20 and August 20, 2020. The sensitivity, specificity, positive, and negative predictive values, and the area under the ROC curve (AUC) of each syndromic pattern (standard case definitions and alternative case definition patterns from Latent Class Analysis (LCA)) were compared and plotted. Results. Among 7,784 hospitalized patients tested for COVID¬19 and included in the analyses, 2,233 (28, 7%) had RT-PCR confirmed COVID-19. The symptoms of fever & chills, cough, breathing difficulty, myalgia, sore throat, headache; and the signs of body temperature >37.8, pharyngeal exudate, and abnormal chest radiography were informative in all syndromic patterns. Among latent classes, symptom-class 3 that was comprised of fever & chills, cough, and breathing difficulty had the greatest AUC. While, among standard syndromic patterns, the WHO-acute respiratory infection (ARI), suspected-COVID-19 and probable-COVID-19 definitions had the greatest sensitivity and AUC. Conclusion. The WHO ARI, suspected-COVID-19, and probable-COVID-19 patterns were the most sensitive for detecting COVID-19 infection among hospitalized patients. However, alternative syndromic patterns can be used in case high specificity is required.
Contained Hypopharyngeal and Cervical Esophageal Perforation Masquerading as Retropha...
Theodore Klug
Courtney Shires

Theodore Klug

and 1 more

October 22, 2020
Esophageal perforation is most commonly caused by endoscopic instrumentation of the upper GI tract and most commonly presents with chest pain in more than 70% of patients, vomiting, and subcutaneous emphysema.
The coping strategies of community  pharmacists and pharmaceutical services provided...
Kok Pim Kua
Shaun Lee

Kok Pim Kua

and 1 more

October 28, 2021
Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in profound health challenges across the globe. Pharmacists’ readiness to cope with the pandemic is critical in supporting and sustaining the healthcare workforce to meet the challenges.Objective This study aims to examine community pharmacists’ views on their work environment, policies, and preparedness for safe retail patronage to prevent the transmission of COVID-19 and assess the variables influencing coping strategies during the pandemic.Setting An online survey of pharmacists practicing in community pharmacy setting in Malaysia.Method A questionnaire-based, cross-sectional study was conducted in Malaysia to evaluate coping strategies of community pharmacists and pharmaceutical services provided during COVID-19 pandemic. Between May 1 and July 31, 2020, the questionnaire was distributed to pharmacists working in community setting nationwide utilizing a snowball sampling method. Main outcome measure Community pharmacists’ perceptions on safety, resilience, organizational support, and pharmaceutical services offered during COVID-19 pandemic.Results A total of 217 pharmacists participated in the study. The vast majority of community pharmacists reported a positive outlook and were able to balance working with self-care during this period. Most reported to have access to personal protective equipment such as gloves and hand sanitizers. A large proportion of community pharmacies also installed physical barriers in doorways or in front of the counter, put markings on the ground to section areas to ensure physical distancing, and controlled the number of customers who could access the pharmacy during this period. Innovations reported to be implemented included teleconsultations and providing curb-side or drive-through delivery and pickup services.  Conclusion The findings suggest the frontline and essential roles of community pharmacists in delivering pandemic responses, creating the opportunity to determine areas where community pharmacy services can be incorporated to strengthen the public health system and improve patient health outcomes.
Cryptococcemia in a Patient with COVID-19: A Case Report
Mohamad  Khatib
Amna  Ahmed

Mohamad Khatib

and 4 more

October 22, 2020
Cryptococcus neoformans infection is a known cause of meningoencephalitis in immunocompromised patients. However, it is less frequent in immunocompetent individuals. Here we report a case of a 60 years old COVID-19 patient with a history of several co-morbidities who received tocilizumab and corticosteroids, which lead to Cryptococcemia.
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