bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil-Dependent Immune Response Promotes Joint Damage in Hemophilia
Authors: Kaminski Tomasz Waldemar , Katoch Omika , Ragni Margaret V. , Sundd Prithu
Published: December 2023

Background: Hemophilic arthropathy (HA) is the predominant pathophysiology resulting from recurrent joint bleeding in individuals with hemophilia and leads to permanent joint damage, chronic pain and reduced quality of life. Although FVIII replacement therapy or FVIII mimetics like HEMLIBRA have significantly improved the disease outcome, joint bleeding continues to occur in severely hemophilic patients (FVIII<1%). HA starts at an early age and develops progressively over time, warranting the need for a therapy that can intervene the progression of HA. Unfortunately, such therapy does not exist and the etiological mechanism of HA remains poorly understood.

Aim: To determine whether neutrophil Gasdermin-D (GSDMD)-dependent generation of neutrophil extracellular traps (NETs) in in the joint promotes HA.

Methods: Knee joints in FVIII-total knockout (F8 TKO) or littermate WT male mice were injured using a needle . Scoring of the bleeding severity and histology of injured joints were conducted to assess the joint injury in mice.Imaging-flow-cytometry and ELISA assays were used to evaluate the number of circulating NETs in the blood samples of patients diagnosed with HA and mice with following knee injury. Neutrophils from HA patients, F8 TKO mice and matched controls were isolated, activation of GSDMD-pathway components was evaluated in neutrophils using qRT-PCR (gene expression) and western blotting (protein levels and cleavage).

Results: F8 TKO but not control mice manifested unresolved joint injury and severe bleeding 5-days post knee injury. Circulating NETs (cNETs) and cNETs markers llike neutrophil elastase or citrulinated histones were significantly elevated in the plasma of hemophilia patients diagnosed with HA and injured F8 TKO mice but not plasma of control humans or injured WT mice or uninjured F8 TKO mice. Major genes (mRNA levels) associated with GSDMD-mediated NETs generation were significantly elevated in neutrophils of HA patients and injured F8 TKO mice compared to matched controls. Finally, western blot analysis revealed activation of GSDMD pathway in neutrophils isolated from HA patients and F8 TKO mice but not matched controls.

Conclusions: These findings are the first to suggest that GSDMD-dependent generation of NETs contributes to the pathogenesis of HA
Modulating Nucleotide Metabolism Enhances Prime Editing in Hematopoietic Stem and Progenitor Cells
Authors: Levesque Sébastien , Bauer Daniel E.
Published: December 2023

Therapeutic prime editing (PE) of hematopoietic stem cells (HSCs) holds great potential to correct pathogenic mutations causative of severe blood disorders. While recent advances have improved the technology, efficient prime editing remains challenging in primary hematopoietic cells. Since SAMHD1 has been identified as an antiviral factor restricting the nucleotide pool available for reverse transcription and virus replication, we hypothesized that modulating this metabolic pathway could enhance reverse transcription and thus prime editing in HSCs. We devised strategies to modulate nucleotide metabolism by supplementing deoxynucleosides (dNs) and delivering the viral accessory protein Vpx using virus-like particles (VLPs). Exogenous dNs supplementation and Vpx-mediated proteasomal degradation of SAMHD1 markedly increased PE efficiency in HSPCs from different healthy donors from an average of 14% to 32% editing with the PE2max system, and from 51% to 70% editing with the PE3max system. Supplementing individual dNs or all dNs minus one also boosted prime editing, but all four dNs were needed for maximal enhancement of PE from an average of 41% to 64% editing at ATP1A1. Using a prime editing guide RNA designed to correct the HBB-E6V mutation causative of sickle cell disease, we achieved an average of 58% and 44% editing with the PE3max and PE3bmax systems, respectively. Modulation of nucleotide metabolism also ameliorated prime editing in both resting and activated CD3 + T cells, although to a lesser extent than in HSPCs. Of relevance, our strategies had little to no impact on PE in K562 and Jurkat cells, suggesting that nucleotide metabolism does not restrict PE in cancer cell lines. Altogether, modulation of nucleotide metabolism should enhance prime editing to facilitate the clinical translation of gene therapies for severe blood disorders. This work highlights a key metabolic restriction for therapeutic prime editing of primary cells and could help design future approaches to engineer quiescent HSCs in vivo.
Association of Hospitalist Care and Outcomes on an Inpatient Elective Anticancer Therapy Service
Authors: Vaughn John L , Merl Man-Yee , Morris Jensa C , Gould Rothberg Bonnie E
Published: December 2023

Background:

Hospitalist care is becoming increasingly common at cancer centers. Here, we assess the impact of oncology hospitalist care on quality outcomes on an inpatient elective anticancer therapy service for patients with leukemia and lymphoma.

Methods:

On July 26, 2021, the Smilow Cancer Hospital transitioned the elective anticancer therapy team from a hematologic oncologist-led traditional service (TS) to an oncology hospitalist-led service (HS). We compared quality outcomes for patients with leukemia and lymphoma requiring elective anticancer therapy who were admitted during two parallel 18-month periods (TS: July 1, 2018 to December 31, 2019; HS: July 26, 2021 to December 31, 2022). Longitudinal data analysis using mixed linear regression models with random effects for intercept (individual) and slope (time) were used to estimate the association between service and outcome, accounting for patients with multiple admissions reflecting sequential cycles of chemotherapy. The outcomes were length-of-stay (LOS), time from admission to first anticancer therapy administration, and discharge time of day. Models were adjusted for age, sex, race/ethnicity, diagnosis, anticancer therapy type, Severity of Illness index, and total elapsed time since cycle 1/day 1 of the index regimen.

Results:

The study included 161 patients, 59 from the TS and 102 from the HS. There were 65 patients with leukemia and 96 with lymphoma. No significant differences in median age, sex, race/ethnicity, or severity of illness index between services were observed (p>0.05). The most common anticancer regimen was etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone (EPOCH) for lymphoma (TS n=16 (27%); HS n=31 (30%)). For anticancer regimens with a fixed number of treatment days, after adjustment, we observed a significant reduction of length of stay that exceeded one full day (TS=6.09 days (95% CI: 6.09, 6.95 days); HS=3.82 days (95% CI:3.48, 4.16 days); p<0.001), the adjusted mean time from admission to first anticancer therapy administration decreased by 4.12 hours (95% CI: 0.66, 7.59 hours; p<0.001), and the adjusted mean discharge time decreased by 66 minutes (95% CI: 9, 211 minutes; p=0.01) ( Table 1). For those regimens that required variable monitoring for post-treatment methotrexate clearance or tumor lysis syndrome, no significant difference in outcomes was noted (p>0.05).

Conclusions:

Hospitalist care on an inpatient elective anticancer therapy service was associated with significant improvements in LOS, time from admission to anticancer therapy administration, and discharge time.
A Retrospective Study of Patient Characteristics, Treatment Patterns and Outcomes in Patients with Primary CNS Lymphoma
Authors: Curley Thomas , Wei Wei , Cordova Christine , Peereboom David , Lobbous Mina , Winter Allison
Published: December 2023

INTRODUCTION: Primary CNS lymphoma (PCNSL) is a rare lymphoma subtype. Treatment with whole brain radiotherapy (WBRT) resulted in high response rates but poor overall survival and modern therapy typically involves combination chemotherapy regimens that include rituximab and high dose methotrexate and, in some cases, followed by consolidative chemotherapy such as autologous stem cell transplantation (ASCT). However, there is no standard regimen, and the choice is institutional and/or physician preference. We performed a single institution retrospective study evaluating the outcomes of patients with PCNSL with focus on outcome stratified by POD24.

METHODS: We performed a retrospective analysis of patients with PCNSL at Cleveland Clinic between January 1, 2010 to December 31, 2020, at the Cleveland Clinic. Patients were excluded if there was any evidence of disease outside of the CNS. Progression-free survival (PFS) and overall survival (OS) after diagnosis were estimated using the Kaplan-Meier method and compared by log rank test. OS was estimated for patients with an event within 24 months (POD24) from the time of this event to death or last follow up.

RESULTS: Data from 80 consecutive eligible patients were analyzed with a median follow up of 44 months. The median age at diagnosis was 63 (range 24-87) and 55% were female. Only a small minority of patients were being treated with immunosuppressants at diagnosis (12%). Of the patients receiving induction therapy, 35% received R-MPV, 20% received R-HDMTX, 4% received HD-MTX alone, 4 % received WBRT as a frontline treatment. 16% of patients received no therapy. The overall response rate to induction therapy was 62% (56% CR and 6% PR). The majority of patients did not receive consolidation treatment (59%). Of those who did receive consolidative therapy, non-myeloablative high dose cytarabine was the most frequently used strategy. Thirty-six patients progressed (45%) and of these, the majority (67%) occurred within 24 months of starting therapy. For the entire cohort, the median PFS was 16 months, and the median OS was 32 months. The 1-year and 5-year OS rates were 66% and 34%, respectively. An ECOG performance status of 0 or 1 was associated with significantly improved PFS and OS (p < 0.0001 for both. Median OS after PD for patients with POD24 was 6 months [95% confidence interval (CI) 4-NA] with only 42% alive at 1 year.

CONCLUSION: This large retrospective study evaluating all patients with B-cell NHL PCNSL with extended follow up shows that the majority of progressive events occur within 24 months and is associated with poor outcomes. Rituximab and polychemotherapy regimens are now favored over rituximab and methotrexate alone to improve response rates. Our data show that emphasis on strategies for consolidation such as high dose chemotherapy and autologous transplantation are needed to prevent progression.
KF1601, a Novel Orally Bioavailable Inhibitor of BCR-ABL1 T315I without Inducing Thrombotic Microangiopathy
Authors: Ahn Sung-Min , Kim Dong-Wook
Published: December 2023

Targeting Bcr-Abl with tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of chronic myeloid leukemia (CML) by significantly improving patients' survival. However, the gatekeeper mutation T315I confers resistance to TKIs targeting Bcr-Abl, presenting a formidable task in CML's clinical management. Ponatinib significantly reduces the mortality of CML patients with Bcr-Abl T315I, but often accompanies severe, life-threatening side effects. Herein, we report KF1601, a novel orally bioavailable TKI: 1) KF1601 inhibited kinase functions of both Bcr-Abl WT and Bcr-Abl T315I with nanomolar IC 50 values; 2) KF1601 and ponatinib had similar potency in terms of inhibiting CRKL phosphorylation, which correlates to major molecular responses in CML patients. 3) In murine models using Ba/F3 Bcr-Abl T315I cell line, it showed promising in vivo antitumor efficacy, comparable to that of ponatinib; 4) In animal models, it did not cause thrombotic microangiopathy, a major mechanism of ponatinib's toxicity. In summary, KF1601 is a promising drug candidate for safely treating CML patients with drug-resistant Bcr-Abl T315I mutation.
The ‘Weekend Effect’ on Immune Cytopenia: Insights from the National Inpatient Sample Database
Authors: Mahmoud Amir , Kharel Himal , Srivastava Arnav , Jain Tripti , Orakzai Abdullah , Mostafa Mariam A , Neupane Niraj , Eltaher Basant , Yassin Heba , Abdelhay Ali
Published: December 2023

Introduction: Outcomes for weekend versus weekday admissions for immune cytopenias including immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), and autoimmune hemolytic anemia (AIHA)/Evan's Syndrome are explored in this abstract.

Methods: A query of the 2012-2019 National Inpatient Sample was performed for primary hospitalizations with immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), and autoimmune hemolytic anemia (AIHA)/Evan's Syndrome using ICD-9/10 codes. Demographics, comorbidities, and outcomes were identified. Univariate analysis with t-tests or chi-square performed as appropriate. A 1:1 nearest neighbor propensity score matched cohorts was generated for each of the ITP, TTP and AIHA/Evan's hospitalization dataset. Variables with standardized mean differences >0.1 used in multivariate regression to generate adjusted odds ratios (AOR)/β-coefficients for weekend admission status on outcomes. Significance was set at an alpha level of <0.05. All analysis performed in SPSS versions 26.

Results: 24,325, 2992,and 7,609 hospitalizations were included with 4592, 656, and 1468 weekend admissions in ITP, TTP, and AIHA/Evan's respectively. Propensity matched cohorts were generated adjusting for age, sex, race, median household income and co-morbidities including DM, CHF, CKD/ESRD, and liver disease. The results showed significantly higher, almost two-fold, in-hospital mortality in AIHA for weekend admissions (Odds ratio (OR): 1.85, CI 1.20-2.85, p-value=0.005). In addition, there was significantly higher risk of circulatory shock and mechanical ventilation requirement for weekend admissions in AIHA along with significantly increased length of hospital stay and total hospital charges. TTP patients also showed similar trend towards higher mortality with significantly higher incidence of AKI and increased length of stay for weekend admissions. There was no significant difference seen in ITP. The results are summarized in table 1. These results are partly in agreement with findings of Manadan et al study, which showed lower rate of procedures and higher adjusted mortality for general inpatient admissions in weekends.

Conclusion: Weekend admissions showed poorer outcomes especially in AIHA and TTP. Although the exact reasons are unknown, decreased staffing and procedural availability may be responsible for such findings. Further studies are needed to clarify the steps needed to decrease adverse outcomes for weekend admissions.
Association between Iron Deficiency Anemia and Thrombosis, a Population Based Study
Authors: Laber Eric Nathan , Laber Damian A
Published: December 2023

Iron deficiency anemia (IDA) has been associated with thrombosis in children, but this association has not been appropriately studied in other age groups. We hypothesize that IDA is a risk factor for thrombosis in all populations. The aim of our study is to evaluate the association between iron deficiency anemia and different types of thrombosis in all patients.

Methods: We searched the medical records of all patients evaluated at a large hospital and outpatient medical center in Tampa, Florida utilizing the International Classification of Diseases 10th Edition (ICD-10). This coding system assigns standard acronyms to conditions, symptoms, and other factors of disease. We used the codes for iron deficiency anemia of all types, venous embolism and thrombosis, cerebrovascular disease, and retinal vascular occlusion. We then combined the codes in the database search to obtain the total number of patients with these conditions. Finally, we performed simple statistical analysis to compare the number and percentage of patients with thrombosis and IDA to patients with thrombosis and without IDA.

Results: 2,539,231 patients were included in our database between 2010 and July 31st 2023. The age of this population was between 0-102 years-old. IDA was present in 66,693 patients (2.63%), venous embolism and thrombosis was present in 36,523 individuals (1.43%), cerebrovascular thrombosis was present in 14,159 patients (0.56%), and retinal vascular occlusion was present in 1,506 individuals (0.06%). Out of the 66,693 patients with IDA, 7,554 (11.3%) had venous embolism and thrombosis, 14,159 (0.56%) had cerebrovascular thrombosis, and 1,506 (0.06%) had retinal vascular occlusion. Out of the 2,472,538 patients without IDA, 28,969 (1.17%) had venous embolism and thrombosis, 12,172 (0.49%) had cerebrovascular thrombosis, and 1,276 (0.05%) had retinal vascular occlusion. When comparing the percentage of patients with IDA versus no-IDA, venous embolism and thrombosis was 10 times more prevalent, cerebrovascular thrombosis was 6 times more prevalent, and retinal vascular occlusion 6 times more prevalent in patients with IDA than in those without IDA in all age groups combined.

Conclusions: In this population based study, the incidence of thrombosis was 6-10 times greater in patients with IDA compared to no-IDA. Our data suggests that IDA is a risk factor for thrombosis in all patients. Prospective studies might be needed to confirm our findings. Finally, our data suggests that treatment of IDA might decrease the risk of thrombosis.
Survival of Patients with Transformed Marginal Zone Lymphoma in the United States: A Population-Based Cohort Study
Authors: Vaughn John L , Epperla Narendranath
Published: December 2023

Background: Marginal zone lymphomas (MZLs) are a heterogenous group of indolent non-Hodgkin lymphomas that include extranodal MZL of mucosa-associated lymphoid tissue (EMZL or MALT lymphoma), nodal MZL (NMZL), and splenic (SMZL). All three subtypes can transform to diffuse large B-cell lymphoma (DLBCL). However, the cumulative incidence of histologic transformation (HT) and survival of patients with transformed MZL (t-MZL) in the US population have not been reported to date. Hence, we sought to estimate the risk of HT and relative survival (RS) in patients diagnosed with MZL in USA using a population-based study.

Method: We conducted a population-based cohort study of t-MZL using the Surveillance, Epidemiology, and End Results-17 database. We included adults diagnosed with MZL in the US between 2011-2015. This time period was selected to provide a contemporary estimate of survival and allow for adequate follow-up. We identified patients with t-MZL by following patients with MZL and identifying those patients with subsequent diagnoses of DLBCL. All patients with t-MZL had biopsy-proven HT. We estimated the post-transformation RS of patients with t-MZL using flexible parametric survival models with 5 degrees of freedom for the baseline cumulative hazard. We compared the survival of the different MZL subtypes using multivariable modeling after adjusting for age, year, race, Ann Arbor stage, B symptoms, and geographic location. P values less than 0.05 were considered statistically significant.

Results: A total of 5372 patients with MZL were included in the study. There were 3446 (64.2%) patients with EMZL, 1485 (27.6%) with NMZL, and 441 with SMZL (8.2%). Among the 5372 patients, 121 (2.3%) had biopsy-proven HT after a median follow-up of 6.2 years (95% confidence interval (CI), 6.1-6.3). HT was associated with decreased survival for patients with MZL ( Figure 1A). Among the MZL subtypes, SMZL was the most likely to develop HT (24/441, 5.4%), followed by NMZL (49/1436, 3.3%) and EMZL (48/3398, 1.4%) ( P < 0.001) despite similar follow-up between groups. The 5-year post-transformation RS was highest for t-EMZL (61%) followed by t-NMZL (51%) and t-SMZL (46%) (Figure 1B). On multivariable analysis, however, the subtype of MZL was not a significant predictor of RS. In addition, there were no significant predictors of RS identified among the study covariates.

Conclusion: This is the first population-based study to date reporting outcomes associated with t-MZL in the USA. The risk of HT in MZL may vary depending on the subtype of MZL with cumulative incidence of 1.4-5.4% observed after 6 years of follow-up in the contemporary era. HT was associated with increased mortality irrespective of MZL subtype. Among the MZL subtypes, SMZL was most likely to develop HT and had the lowest estimated 5-year RS. Additional studies are needed to better understand factors associated with prognosis in t-MZL.
Statewide Burden and Trends of Acute Myeloid Leukemia in the United States between 1990-2019: A Benchmarking Analysis for the Global Burden of Disease Study 2019
Authors: Gadhiya Dhruvkumar , Bhatt Parjanya , Christian Cleris , Singh Gauravdeep , Dhawan Arushi , Amin Vishrant , Patel Juhi , Desai Hardik Dineshbhai
Published: December 2023

Background: Acute myeloid leukemia (AML) ranks as the 15th leading cause of death, accounting for 1.75% of all cancer-related deaths in the United States of America (USA) in 2019, following Myeloma. Despite its significance, statewide disparities in AML burden have not been previously studied. Thus, this research aimed to assess the burden and trends of AML across the USA over the last three decades, spanning from 1990 to 2019.

Method: Employing the Global Burden of Disease methodology, we evaluated AML prevalence, incidence, mortality, and disability-adjusted life years (DALYs) using standardized approaches and statistical modeling. The results were presented in absolute counts and age-standardized rates (per 100,000 person-years).

Results: The total number of AML prevalence cases rose from 10,124 (95% uncertainty interval (UI): 9,259-11,482) in 1990 to 21,370 (95% UI: 17,759-24,830) in 2019. Correspondingly, deaths increased from 6,849 (95% UI: 6,301-7,724) in 1990 to 13,620 (95% UI: 11,632-14,664) in 2019, while DALYs increased from 185,960 (95% UI: 171,985-210,122) in 1990 to 301,526 (95% UI: 268,606-323,608) in 2019. The age-standardized incidence rate (ASIR) rose from 2.75 (95% UI: 2.52-3.09) to 3.23 (95% UI: 2.71-3.73) cases per 100,000 from 1990 to 2019. Similarly, the age-standardized mortality rate (ASMR) increased from 2.20 (95% UI: 2.03-2.48) to 2.54 (95% UI: 2.19-2.72) cases per 100,000 during the same period. In 2019, the greatest AML incidence was observed in California (1,677), followed by Florida (1,268) and Texas (1,155), while the lowest incidence was observed in the District of Columbia (24). Regarding the annual percentage of change (APC), the highest percentage increase in deaths was observed in Nevada (328%), followed by Alaska (224%), while the District of Columbia had the lowest APC (6%) from 1990 to 2019. In terms of incidence, Nevada (332%) and Arizona (227%) had the highest APC during the same period. The age group of 70-74 years had the highest number of deaths (2,264) and incidence (2,665), as well as DALYs (43,918) in 2019. Notably, the older age groups exhibited the highest APC in deaths and incidence. Males had a higher burden of AML compared to females.

Conclusion: Our study underscores significant disparities in AML burden across different states in the USA from 1990 to 2019. We have also identified that males and elderly individuals face a higher likelihood of AML burden. Consequently, policymakers must prioritize enhancing healthcare systems, advancing early diagnosis and treatment approaches, and promoting health education to reduce individual exposures to relevant risk factors.
Beneficial Role of Erythrocyte Sphingosine 1-Phosphate in Preventing Renal Macrophage Polarization and Fibrosis through Combating HIF-1α-Dependent Creatine Phosphate Shuttle
Authors: Xie Tingting , Chen Changhan , Wang Yiyan , Li Zhenjiang , Brown Benjamin C. , Kellems Rodney E. , Zhang Weiru , D'Alessandro Angelo , Xia Yang
Published: December 2023

Introduction: Erythrocytes, the major reservoir and supplier for plasma sphingosine 1 phosphate (S1P), is a potent biolipid signaling via its specific receptors responsible for immune cell trafficking and function. Current evidence has revealed that erythrocyte intracellular S1P has its own function to promote oxygen (O 2) delivery to counteract tissue hypoxia.

Aim: To understand whether O 2 delivery mediated by erythrocyte S1P is involved in tissue macrophage polarization and fibrosis.

Methods and Results: Genetic ablation of erythrocyte SphK1 (the only enzyme to generate S1P in erythrocyte, eSphK1 -/-) resulted in less O 2 delivery from erythrocytes, thus leading to severe renal hypoxia, damage and fibrosis in angiotensin II induced hypertensive kidney disease mouse model. Surprisingly, although plasma S1P level was reduced to 50% in Ang II-infused eSphK1 -/- mice, these mice displayed preferentially elevated pro-fibrosis M2 macrophages surrounding the hypoxic renal tubules. Surprisingly, there was no significant difference of S1P level in either kidney or renal macrophages between Ang II-infused controls and eSphK1 -/- mice, ruling out the possibility of difference of kidney or macrophage S1P levels responsible for renal M2 macrophage polarization. Metabolically, untargeted high-throughput metabolic profiling in macrophages purified from mouse kidney revealed a substantial reduction of amino acids (AAs) and fatty acids (FAs) but increased creatine. We further validate this in vitro by 13C 6, 15N 4-labeled arginine tracer. Hypoxia (1~2% O 2) promoted increased 13C 2-labeled creatine (arginine downstream metabolite) in murine bone marrow derived macrophages (BMDMs) time dependently. At cellular and molecular level, we further demonstrated that hypoxia signaling via HIF-1a directly enhanced IL-4 induced M2 polarization of BMDMs as well as expression of Ckb (a gene encoding creatine shuttle), which can be reversed by Chrysin (an HIF-1α inhibitor). Preclinical studies revealed that chrysin rescued the severe renal damage in eSphK1 -/-mice manipulated with unilateral ureteral obstruction (UUO) and prevented development of chronic kidney disease (CKD) in the control mice. Translational research validated mouse findings in kidney tissue of CKD patients.

Conclusion: Our work has revealed that erythrocyte S1P combats HIF1α-dependent creatine shuttle, renal macrophage polarization and fibrosis and highlighted potential diagnostic and therapeutic possibilities for macrophage polarization and renal fibrosis.
Comparative Outcome Analysis of Nodular Lymphocyte-Predominant Hodgkin Lymphoma Vs Classical Hodgkin's Lymphoma - a SEER Based Study
Authors: Shah Anish , Budhathoki Pravash , Karki Ujjwal , Neupane Niraj , Khanal Sneha
Published: December 2023

Introduction

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a slower-growing variant of Hodgkin lymphoma that is uniquely characterized by its growth pattern and cellular appearance. While patients with NLPHL tend to demonstrate more promising prognoses than their counterparts with classical Hodgkin lymphoma (CHL), recent comparative studies remain limited. The objective of this study was to investigate the disparities in survival rates between NLPHL and CHL patients, accounting for variations in patient demographics and disease attributes.

Methodology

We utilized Surveillance, Epidemiology, and End Results (SEER) 17 registries database to identify patients diagnosed with NLPHL and CHL between 2000 - 2020. Univariate survival analysis was done using a Kaplan Meir plot with a log-rank test, and the Cox proportion hazard regression model was used for multivariate survival analysis.

Results

A total of 2,723 NLPHL cases and 42,581 CHL cases were included in the study. The median age of NLPHL patients stood at 44 years, whereas for CHL patients it was observed to be 38 years. Over an 83-month median follow-up, NLPHL demonstrated superior 5-year (92.2%) and 10-year (83.84%) survival rates compared to CHL (82.45% and 75.45%, respectively). When controlled for all available characteristics, NLPHL showed a significantly higher overall survival (HR: 2.373; 95% CI, 2.131 - 2.644; P<.001) than CHL. For those diagnosed with NLPHL, our data indicated that patients who underwent radiation therapy had better survival rate (HR: 1.98; 95% CI, 1.55 - 2.53; p<.001). Additionally, younger age and male gender were associated with a more favorable prognosis.

Conclusion

Our analysis highlights the superior survival outcomes for NLPHL patients as compared to those with CHL, even when accounting for available patient and disease characteristics. The further enhanced survival rates observed in NLPHL patients undergoing radiation therapy suggests potential for more tailored therapeutic approaches. Factors such as younger age and male gender were also identified as indicative of a more favorable prognosis, underscoring the need for further exploration of demographic and clinical influences on survival outcomes in Hodgkin lymphomas.
National Mortality Outcomes of Acute Chest Syndrome Hospitalization during the COVID-19 Pandemic
Authors: Olafimihan Ayobami , Turk Ekrem , Ozogbo Stanley , Cuartas-Mesa Maria Cristina , Fawehinmi Praise , Shaka Hafeez
Published: December 2023

Introduction

Sickle cell disease (SCD) is an hereditary hemoglobin disorder characterized by repeated episodes of severe acute pain, acute chest syndrome (ACS) and other complications. The average life expectancy of SCD patients remains 20 years less than the general population, and ACS is the leading cause of mortality. This retrospective study describes the effect of the COVID-19 pandemic on epidemiologic trends and outcomes of Acute Chest Syndrome.

Methods

The National Inpatient Sample (NIS) database from 2016 to 2020 was searched for hospitalizations with ACS as the principal diagnosis using Clinical Classifications Software Refined codes. The ACS admission rate for each calendar year was obtained as admission per 10,000 SCD adults hospitalized. The primary outcome was a comparison of inpatient mortality, and the secondary outcomes were the length of hospital stay (LOS) and total hospital charge (THC) between prepandemic (2019) and pandemic years (2020).

Results

In 2019 (prepandemic), there were 5,160 hospitalizations for ACS, accounting for 624 per 10,000 adult SCD hospitalizations. In 2020 (pandemic), there were 4,285 patients hospitalized for ACS, accounting for 540 per 10,000 adult SCD hospitalizations. The mean age of admission was similar for both years (31.5 vs 32 years, P=0.143), and there was no significant difference in age categories when both years were compared. The gender distribution was similar during both periods (females: 45.6 vs 46.7%, p=0.68). The racial distribution was predominantly blacks with no significant difference during both year (92 vs 92%, p=0.3). There was no significant difference in hospitalizations with regard to insurance status, hospital region, or hospital size between both years.

There was a three-fold increase in overall proportion of ACS inpatient mortality in the pandemic year of 2020 compared to the prepandemic level (0.6% vs 1.9%, P=0.009). Proportion of mortality among women had a five-fold increase (0.4% vs 2.3%, P=0.02). There was a four-fold increase in mortality proportions among the Black population (0.5% vs 2%; p=0.007). Mortality outcomes were similar over both years when stratified for income quartiles and hospital regions.

The LOS during the pandemic was similar to the prepandemic level (6.5. vs 7.4days, P=0.563). Also, there was no statistically significant difference in the total hospital charge ($61,515 vs $80,191, P=0.108).

Conclusion

This study depicts a statistically significant increase in inpatient mortality outcomes of Acute chest syndrome during the pandemic period. However, the length of hospital stay and total hospital charge were similar. Further studies need be conducted to evaluate the long-term effect of the COVID-19 pandemic on SCD.
Primary Pancreatic Lymphoma: An Analysis of the National Cancer Database
Authors: Abushalha Kamelah , Silberstein Peter T.
Published: December 2023

Background: Primary pancreatic lymphoma (PPL) is a rare entity, accounting for fewer than 2% of extranodal malignant lymphomas and 0.5% of all pancreatic masses. Fewer than 150 cases of PPL have been reported in the English language medical literature. We aimed to utilize the National Cancer Database (NCDB) to investigate the clinicopathological features and prognostic factors in PPL.

Methods: The NCDB for Non-Hodgkin lymphoma was used to identify 2130 patients diagnosed with PPL (2004 and 2020). The database was used to examine clinicopathological features. Survival analysis was done by Kaplan-Meier. Cox proportional hazards was adopted for prognostic variable evaluation.

Results: Most PPL patients were males (58.5%) and white (87.7%), mean age at diagnosis was 67.38 years. Histologically 59.6% were diffuse large B-cell. 14.9% Follicular, 2.6 % Burkitt, & 15.8% Lymphoma NOS. Regarding treatment 71.5% of patients received chemotherapy. Immunotherapy given in 21.9%. Radiation in 12.1%, and 7.3% received some form of surgical treatment. Median survival was 85.32 months (CI 79.79-90.84). Using Cox hazard regression, the following factors were statistically significant (p<0.001): Age >60 (HR: 2.36,CI 1.9-2.8), increasing Charlson-Deyo Score, DLBL histology (HR:0.57,CI 0.45-0.72), stage 3 (HR:1.9,CI 1.6-2.2), Chemotherapy (HR 0.4,CI 0.34-0.46),and immunotherapy (HR 0.61,CI0.62-0.89)

Conclusion: This is the most comprehensive study to date to utilize the NCDB to study the characteristics and prognostic factors of patients with PPL. DLBL histology, chemotherapy and immunotherapy are associated with reduced risk of death.
Incidence and Prognosis of Primary Malignancies in Ataxia-Telangiectasia Patients: A Report from the Ataxia-Telangiectasia Clinical Center (ATCC)
Authors: Sharma Richa , Magnarelli Aimee , Liu Qi , Wang Fan , Yasui Yutaka , Ehrhardt Matthew J. , Lederman Howard
Published: December 2023

Biallelic germline mutations in the ATM gene result in Ataxia-Telangiectasia (AT), a classic DNA repair disorder associated with a high incidence of primary malignancies. The lack of standardized cancer treatment approaches for patients with AT is believed to contribute to poor survival after diagnosis. Robust characterization of the incidence, outcomes, and ATM variant enrichment of large cohorts of individuals with AT who develop malignancies are needed to inform therapeutic decision-making.

The AT Clinical Center (ATCC) at Johns Hopkins Hospital is a large, retrospective cohort that prospectively collects outcomes data on individuals diagnosed with AT in the US. Standardized incidence ratios (SIRs) were used to compare cancer incidence to that of age-, sex-, and year-matched US general population using the SEER database. Standardized mortality ratios (SMRs) and mortality rate ratios were used to estimate mortality risk compared to the general population.

Among 508 total participants with AT, 84 developed cancers (16.5%): 39 non-Hodgkin lymphoma (NHL), 7 Hodgkin lymphoma, 16 leukemia (n=13 of T cell origin), and 22 carcinomas. SIRs were 355.9, 67.4, 45.6, and 18.0, respectively. Median (interquartile range) age at cancer diagnosis was 14.3 years (10.3-22.8), with NHL occurring in the youngest (12.4 years, IQR 7.3-16.7) and solid tumors in the oldest (26.3 years, IQR 18.7-29.0) individuals. The SMR was 24.6 (95% CI: 21.1-28.4) for the overall cohort of AT patients and 232.9 (95% CI: 178.1-299.2) among those with cancer. Median survival following a cancer diagnosis was 2.5 years (95% CI: 0.1-14.4). The post-cancer mortality rate ratio was 2.2 (95% CI: 1.1-4.3, p=0.025) comparing AT patients with cancer treated without dose reduction or for whom dosing was unknown (n=24) versus AT patients with cancer who received dose reduced chemotherapy (n= 38). Among those who received chemotherapy (n=62), 11/24 (45.8%, 95% CI: 25.6-67.2) treated with standard dosing and 24/38 (63%, 95% CI: 46.0-78.2) treated with reduced dosing experienced toxicity (p=0.20). ATM variant associations were detected by single variant analysis among 247 patients with AT who had confirmed biallelic ATM mutations via whole exome sequencing.

Individuals with AT are at very high-risk of primary malignancies, of which NHL is most common. Prognosis is poor regardless of standard versus dose reduced chemotherapy regimens, which calls for novel therapies.
Translation, cross-cultural adaptation and measurement proprieties of the German version of the Allodynia Symptom Checklist (ASC-12)
Authors: Marusich Tetiana , Szikszay Tibor M , Sennholz Anne , Luedtke Kerstin , Carvalho Gabriela F.
Published: December 2023

Background

Cutaneous allodynia is highly prevalent among migraineurs and is associated with a poor prognosis. The Allodynia Symptom Checklist (ASC-12) is a comprehensive questionnaire to identify the presence and severity of allodynia. Our aim was to translate and adapt the ASC-12 to German and evaluate its measurement properties.

Methods

Following the COSMIN guidelines, 80 migraine patients were enrolled in the study to evaluate the stages of translation (n=30) and measurement propriety assessment (n=50), respectively. After reaching a final version, the German ASC-12 was assessed for structural validity, internal consistency, test-retest reliability, construct validity and absolute agreement, using mechanical and thermal pain thresholds as reference method.

Results

The German version of the ASC-12 presented an adequate structural validity compatible with the original version of the questionnaire. Its internal consistency ranged from 0.70 to 0.80 considering the total score and the thermic, static and dynamic mechanic subdomains. The total score presented excellent reliability (ICC: 0.85) with a standard error of measurement of 1.15 points and smallest detectable change of 3.40 points. ASC-12 total scores were correlated with headache intensity (r=0.38, p=0.004), headache disability (r=0.37, p=0.004) and cold pain thresholds (r=0.28, p=0.025). The thermic allodynia ASC-12 scores were correlated with cold (r=0.36, p=0.005) and heat (r=-0.30, p=0.010) pain thresholds, while the static mechanical allodynia ASC-12 scores correlated with mechanical pain threshold (r=0.29, p=0.019) and with mechanical pain sensitivity (r=0.24 to 0.28, p< 0.045). Despite no significant bias between methods, quantitative sensory testing (QST) results and ASC-12 scores tend to disagree.

Conclusion

The German version of the ASC-12 is available for research and clinical settings and presented adequate measurement proprieties, as the original version. Despite the correlation between the ASC-12 and QST, one method cannot be replaced by the other.
HostNet: improved sequence representation in deep neural networks for virus-host prediction
Authors: Ming Zhaoyan , Chen Xiangjun , Wang Shunlong , Liu Hong , Yuan Zhiming , Wu Minghui , Xia Han
Published: December 2023

Background

The escalation of viruses over the past decade has highlighted the need to determine their respective hosts, particularly for emerging ones that pose a potential menace to the welfare of both human and animal life. Yet, the traditional means of ascertaining the host range of viruses, which involves field surveillance and laboratory experiments, is a laborious and demanding undertaking. A computational tool with the capability to reliably predict host ranges for novel viruses can provide timely responses in the prevention and control of emerging infectious diseases. The intricate nature of viral-host prediction involves issues such as data imbalance and deficiency. Therefore, developing highly accurate computational tools capable of predicting virus-host associations is a challenging and pressing demand.

Results

To overcome the challenges of virus-host prediction, we present HostNet, a deep learning framework that utilizes a Transformer-CNN-BiGRU architecture and two enhanced sequence representation modules. The first module, k-mer to vector, pre-trains a background vector representation of k-mers from a broad range of virus sequences to address the issue of data deficiency. The second module, an adaptive sliding window, truncates virus sequences of various lengths to create a uniform number of informative and distinct samples for each sequence to address the issue of data imbalance. We assess HostNet's performance on a benchmark dataset of “Rabies lyssavirus” and an in-house dataset of “Flavivirus”. Our results show that HostNet surpasses the state-of-the-art deep learning-based method in host-prediction accuracies and F1 score. The enhanced sequence representation modules, significantly improve HostNet's training generalization, performance in challenging classes, and stability.

Conclusion

HostNet is a promising framework for predicting virus hosts from genomic sequences, addressing challenges posed by sparse and varying-length virus sequence data. Our results demonstrate its potential as a valuable tool for virus-host prediction in various biological contexts. Virus-host prediction based on genomic sequences using deep neural networks is a promising approach to identifying their potential hosts accurately and efficiently, with significant impacts on public health, disease prevention, and vaccine development.
Comparison of intrathecal low-dose bupivacaine and morphine with intravenous patient control analgesia for postoperative analgesia for video-assisted thoracoscopic surgery
Authors: Guo Miao , Tang Suhong , Wang Yixin , Liu Fengxia , Wang Lin , Yang Dawei , Zhang Jianyou
Published: December 2023

Background

Thoracoscopic surgical techniques continue to advance, yet the intensity of postoperative pain remains significant, impeding swift patient recovery. This study aimed to evaluate the differences in postoperative pain and recuperation between patients receiving intrathecal morphine paired with low-dose bupivacaine and those administered general anesthesia exclusively.

Methods

This randomized controlled trial enrolled 100 patients, who were allocated into three groups: Group M (5 μg/kg morphine intrathecal injection), Group B (5 μg/kg morphine combined with bupivacaine 3 mg intrathecal injection) and Group C (intrathecal sham injection). The primary outcome was the assessment of pain relief using the Numeric Rating Scale (NRS). Additionally, intraoperative remifentanil consumption was quantified at the end of the surgery, and postoperative opioid use was determined by the number of patient-controlled analgesia (PCIA) compressions at 48 h post-surgery. Both the efficacy of the treatments and any complications were meticulously recorded.

Results

Postoperative NRS scores for both rest and exercise at 6, 12, 24, and 48 h were significantly lower in groups M and B than in group C (P<0.05). The intraoperative remifentanil dosage was significantly greater in groups M and C than in group B (P<0.05), while there was no significant difference between groups M and C (P>0.05). There was no significant difference in intraoperative propofol dosage across all three groups (P>0.05). Postoperative dosages of both sufentanil and Nonsteroidal anti‐inflammatory drugs (NSAIDs) were significantly less in groups M and B compared to group C (P<0.05). The time of first analgesic request was later in both groups M and B than in group C (P<0.05). Specific and total scores were elevated at 2 days postoperative when compared to scores at 1 day for all groups (P<0.05). Furthermore, at 1 day and 2 days postoperatively, both specific scores and total scores were higher in groups M and B compared to group C (P<0.05).

Conclusion

Intrathecal administration of morphine combined with bupivacaine has been shown to effectively ameliorate acute pain in patients undergoing thoracoscopic surgery.

Trial registration

The trial was registered on ClinicalTrials.gov: ChiCTR2200058544, registered 10/04/2022.
MicroRNA-155 targets SOCS1 to inhibit osteoclast differentiation during orthodontic tooth movement
Authors: Jiao Yao , Mi Sicong , Li Xiaoyan , Liu Yitong , Han Nannan , Xu Junji , Liu Yi , Li Song , Guo Lijia
Published: December 2023

Background

MicroRNA-155 (miR-155) is a multifunctional miRNA whose expression is known to be involved in a range of physiological and pathological processes. Its association with several oral diseases has been established. However, the specific role of miR-155 in orthodontic tooth movement remains unclear. In this study, we investigated the impact of miR-155 on osteoclast differentiation and orthodontic tooth movement models, aiming to explore the underlying mechanisms.

Methods

In this experiment, we utilized various agents including miR-155 mimic, miR-155 inhibitor, as well as non-specific sequences (NC mimic & NC inhibitor) to treat murine BMMNCs. Subsequently, osteoclast induction (OC) was carried out to examine the changes in the differentiation ability of monocytes under different conditions. To assess these changes, we employed RT-PCR, Western blotting, and TRAP staining techniques. For the orthodontic tooth movement model in mice, the subjects were divided into two groups: the NaCl group (injected with saline solution) and the miR-155 inhibitor group (injected with AntagomiR-155). We observed the impact of orthodontic tooth movement using stereoscopic microscopy, micro-CT, and HE staining. Furthermore, we performed RT-PCR and Western blotting analyses on the tissues surrounding the moving teeth. Additionally, we employed TargetScan to predict potential target genes of miR-155.

Results

During osteoclast induction of BMMNCs, the expression of miR-155 exhibited an inverse correlation with osteoclast-related markers. Overexpression of miR-155 led to a decrease in osteoclast-related indexes, whereas underexpression of miR-155 increased those indexes. In the mouse orthodontic tooth movement model, the rate of tooth movement was enhanced following injection of the miR-155 inhibitor, leading to heightened osteoclast activity. TargetScan analysis identified SOCS1 as a target gene of miR-155.

Conclusions

Our results suggest that miR-155 functions as an inhibitor of osteoclast differentiation, and it appears to regulate osteoclasts during orthodontic tooth movement. The regulatory mechanism of miR-155 in this process involves the targeting of SOCS1.
The effects of art therapy on quality of life and psychosomatic symptoms in adults with cancer: a systematic review and meta-analysis
Authors: Zhou ShiShuang , Yu MeiHong , Zhou Zhan , Wang LiWen , Liu WeiWei , Dai Qin
Published: December 2023

Background

Cancer-related psychological and physical disorders can mean stressful and painful experiences for patients. Art therapy, a form of complementary and alternative medicine, is an increasingly popular way to decrease emotional stress, alleviate somatic symptoms, and improve quality of life in patients with cancer. However, current systematic reviews have not explored the beneficial effects of art therapy. Moreover, there have been inconsistent findings on the effect of this therapy, and there is insufficient evidence to confirm the effects in adults with cancer. The objective of this study was to determine the efficacy of art therapy in improving quality of life and psychosomatic symptoms in adults with cancer.

Methods

This systematic review and meta-analysis included adults with all kinds of cancer. Six English-language and three large Chinese-language databases were comprehensively searched for relevant studies. Gray literature and references were also checked. The quality of the included studies was evaluated using the Cochrane risk-of-bias assessment tool.

Results

Eight eligible randomized controlled trials conducted in four countries were included. Art therapy improved overall quality of life, but had no significant effect on psychological health or physical health sub-dimensions in women with cancer. Moreover, art therapy alleviated anxiety and depression, but had only a tendency toward an effect on somatic symptoms.

Conclusions

Moderate-quality evidence shows that art therapy is beneficial for women with cancer in terms of improving the overall quality of life and alleviating emotional symptoms (anxiety and depression). However, more high-quality randomized controlled trials are needed to determine the efficacy of this therapy on somatic symptoms.