bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends and Drivers of Avocado Production in Ethiopia: A Review
Authors: Asfaw Efrem , Nigussie Zinash
Published: December 2024

Global avocado production has seen a significant increase over the past few decades. The area harvested and production quantities have grown substantially, reflecting the rising demand for avocados worldwide. In Ethiopia, avocado production has been experiencing significant growth and the Ethiopian government, in collaboration with international organizations has been working intensively for avocado crop development in the country. These efforts have led to an increase in both the area under cultivation, production and productivity. The data from Food and Agricultural Organization indicated that the area under avocado cultivation in Ethiopia was 9,754 ha in 2000 and through up and downward fluctuations, substantial jump were seen in 2020 hitting 30,588 ha. For about more than a decade from 2000-2013, the volume of avocado production reveals a steady increase and the most significant growth were observed from 2016-2020, with production rising to 81,431.76 metric tons in 2017 and reaching 245,335.63 metric tons in 2020. The productivity of avocado in Ethiopia has experienced notable fluctuations in the last two decades. Even though there was a slight decline in subsequent years, the current productivity 5.8tons per hectare remained relatively high compared to the early 2010s. Favorable agro-ecological conditions, growing domestic demand, and government initiatives to promote and produce, high-yield, disease-resistant varieties, nutritional value, development of export markets, establishment of different processing factories in different parts of Ethiopia, government initiative and international support are factors responsible for expansion and development of avocado crop in Ethiopia. However, challenges such as limited access to quality seeds and planting materials, insufficient irrigation systems, very weak market chains, climate change, root rot and pests, low agronomic practices, lack of market and price information, perishability nature of the crop, lack of proper storage, weak access to transportation and extension services still need to be addressed. Addressing the issues, the future of avocado production and productivity in Ethiopia look promising and positive trends, with the potential to contribute significantly to the food security and economic development.
A Unique Case of Pretonamid Resistance on MDR TB Patient: A Case Report
Authors: Yesuf Mustofa , Diress Getachew , Mamo Abraham , Mohammed Abdurehman
Published: December 2024

Background: Pretomanid is a novel medication that belongs to the class of nitroimid-azooxazines. The development of resistance to this novel agent not only complicates clinical management but also poses a threat to public health efforts aimed at controlling TB. This case report highlights the clinical presentation, laboratory findings, and therapeutic implications associated with a patient exhibiting pretonamid resistance. Through this examination, we aim to enhance understanding of resistance mechanisms, underscore the importance of ongoing surveillance, and advocate for refined treatment strategies in the context of MDR-TB management understanding the mechanism of this resistance is crucial for developing effective treatment strategy and improving patient outcome. Case presentation: a sixteen-year-old male patient diagnosed with rifampicin-resistant PTB (RR-PTB) after he presented with a cough of two weeks duration and he is on treatment for RR-PTB, and he is on BpaLM regimen. The third-month second-line phenotypic DST result revealed pretomanid (Pa) resistance. [Stm, INH, RIF, EMB, Pa are resistant, and Bdq, Clf, Dlm, Lfx, Lzd, and Mfx are sensitive]. Clinical Discussion: Following the hospital’s clinical panel team and national TB program expert’s discussion we changed the regimen to individualized (Lfx, Cs, Bdq, Dlm, Cfz and Lzd). Conclusion: Pretomanid resistance in humans reveals a low prevalence but highlight the need for vigilance. And since it’s the incorporated in BPaL regimine and its among the backbone of the regimen we should have to follow the resistance pattern. While facing Pretomanid resistance Consult experts, engage a physician experienced in drug-resistant TB for treatment planning and management, monitor adverse effects closely observe patients for signs of myelosuppression, peripheral neuropathy, and hepatotoxicity during treatment with the BPaL regimen. And also ensure timely susceptibility testing for all components of the BPaL regimen to guide effective treatment adjustments then go for alternative regimen.
Guilt-and Shame-Proneness, Birth-related Post-traumatic Stress and Post-Traumatic Growth in Women with Preterm Birth
Authors: Jarašiūnaitė-Fedosejeva Gabija , Kniežaitė Jovita , Sakalauskienė Ernesta , Ayers Susan , Bogaerts Annick , Riklikienė Olga
Published: December 2024

Mothers of premature infants are at high risk of experiencing birth trauma and poor postpartum mental health. However, for some, this experience can lead to personal growth. This study examines Lithuanian women with preterm births, where birth-related PTSD is notably higher despite a lower preterm birth rate. Given the common emotional responses of guilt and shame, we explore whether proneness to these emotions moderates the relationship between birth-related PTSD and post-traumatic growth. A cross-sectional study was conducted using an anonymous e-survey to collect data. Women (N = 79) who experienced a preterm birth during 2020 to 2021 participated in the study at least 2 months postpartum, completing the City Birth Trauma Scale (City BiTS), the Guilt and Shame Proneness Scale (GASP), and the Post Traumatic Growth Inventory (PTGI). The relationship between birth-related post-traumatic stress and post-traumatic growth was assessed using linear regression, while the roles of guilt and shame proneness in this relationship were evaluated using moderated regression. The results showed that higher birth-related post-traumatic stress symptoms were associated with greater post-traumatic growth. However, proneness to shame-related negative self-evaluation weakened this relationship, particularly in women with very preterm births. These findings suggest that trauma models should incorporate the moderating role of shame in recovery outcomes. Women with very preterm births who are prone to shame may require more focused attention from healthcare specialists, with targeted interventions to address these emotional challenges and enhance post-traumatic growth. Additionally, policy initiatives should prioritize support programs tailored to the unique psychological needs of these women.
Place and sense of place in local manufacturing: How local fashion and textile companies in Norway work with and through place-based tensions
Authors: Andersen Kirsti Reitan , Pedersen Esben Rahbek Gjerdrum
Published: December 2024

The study examines: (1) how place-based organizational tensions arise in the context of local textile and fashion manufacturing, and (2) the strategies employed to address these tensions. Based on interviews with owners and/or managers from Norwegian textile and fashion companies, the study identifies three main categories of place-based tensions: (1) Mission: Belonging vs Performing; (2) Spatial: Belonging vs Organizing; and (3) Competence: Belonging versus Learning. Moreover, the study identifies four interrelated coping strategies used by actors to tackle place-based tensions and strengthen the position of local manufacturing in the global fashion industry. The findings contribute to the existing literature by identifying the key place-based tensions linked to local manufacturing business models and the steps taken by actors to address these oppositional demands in everyday organizational practices. Additionally, the study adds nuance to our understanding of how attachment to place can support organizational change toward practicing sustainability.
Managing and resourcing Nigerian banks’ diasporic operations in the UK: An empirical study
Authors: Sani Kareem Folohunso , Harrison Michael , Adisa Toyin Ajibade
Published: December 2024

This study explores the objectives and operations of the diasporic operations of Nigerian banks in the UK. Its aim is to understand why such banks choose to establish a presence in the UK, how they structure themselves, and how they meet the UK’s regulatory standards. By employing a mixed-method approach – a combination of survey data and semi-structured interviews – this research examines the reasons underlying Nigerian banks’ engagement in diaspora banking, their human resources strategies, and the manifestation of their organisational culture within the UK context. The findings illustrate that Nigerian banks utilise either the subsidiary model or the branch model to cater to the financial needs of Nigerian diaspora communities, facilitate international transactions, and support international investment in Nigeria and Africa more broadly. The usually staffing strategy applied involves a mixture of UK-based employees and Nigerian staff seconded from the banks; headquarters in Nigeria, which ensures that the bank are able to adhere to both UK financial regulations and Nigerian compliance standards. The study’s originality lies in its novel contribution to the operational activities of diaspora banking in the UK.
Shedding Light on Falls: The Effect of Lighting Levels on Fall Risk in Long-Term Residential Care Facilities
Authors: Emad Yasaman , Neef Sonja P. , Taylor Lynne , Kerse Ngaire , Cavadino Alana , Moyes Simon A. , Comber Kate , Wu Xiaojing S. , Molloy Janine , Bacon Catherine J.
Published: December 2024

To compare lighting levels in care facilities with local recommendations and determine their cross-sectional association with fall rate, we recruited residents ( n = 126) from 12 long-term care facilities (mean ± SD age 85.1 ± 7.9 years; 64.3% female). Lighting levels were measured at different times in various areas within facilities, according to each resident’s movements and habitual use of light. Lighting fell short of focused activity recommendations in 57.7% of bedrooms and 68.5% of bathrooms (bathing and toileting areas); 22.8% and 41.9%, respectively, were also below general activity recommendations. Lower bedroom and overall lighting correlated with higher fall rates (all p < .05). Covariate-adjusted negative binomial models showed lighting in dining rooms (incidence rate ratio [IRR] = 0.92 (95% CI 0.87–0.98; p = .005) for 100 lux increase), bathrooms (IRR = 0.87 [0.78–0.98]; p = .016), and overall (IRR = 0.91 [0.83–1.00]; p = .03–.04) predicted lower fall rates. Areas used by care facility residents commonly have lower than recommended lighting levels, which increases fall risk.
Outcomes for older patients with subarachnoid haemorrhage who require admission to an Australian intensive care unit
Authors: Sharman Jeremy , Turner Natasha , Karahalios Amalia , Sansom Ben , Deane Adam M , Plummer Mark P
Published: December 2024

Background:

Advanced age is an independent risk factor for poor outcomes following aneurysmal subarachnoid haemorrhage (SAH). However, Australian data are lacking. Our aim was to evaluate outcomes for older patients admitted to an Australian intensive care unit for management of aneurysmal SAH.

Methods:

We conducted a single centre retrospective observational study looking at adult patients admitted with aneurysmal SAH to an Intensive Care Unit (ICU) over a 10-year period. Patients were grouped by age; <70 years, 70–79 years, ⩾80 years, and were of sufficient complexity to be unsuitable for our neurosurgical high-dependency unit. The primary outcome was in-hospital mortality. Secondary outcomes were ICU and hospital length of stay, and discharge destination.

Results:

Of 372 patients admitted to ICU with aneurysmal SAH, 302 (82%) were younger (<70 years), 46 (12%) were septuagenarians and 24 (6%) were octogenarians. There were no differences between clinical or radiological grade of aneurysmal SAH between age cohorts. When compared to the patients younger than 70 years, there was increased odds of dying for those 70–79 and ⩾80 years (70–79: OR 1.98, 95% CI 0.93, 4.20 p = 0.077; ⩾80: OR 4.01, 95% CI 1.55, 10.35 p = 0.004). There were no associations between age and duration of admission. Only 6% of patients aged ⩾70 years were discharged home alive.

Conclusion:

It was uncommon for patients over 70 years of age who present with a SAH to be discharged home from hospital, and those aged ⩾80 are four times more likely to die in hospital than younger patients.
The effect of preoperative interventions on postoperative outcomes following elective hand surgery: A systematic review
Authors: Babiker-Moore Tahra , Clark Carol J , Kavanagh Emma , Crook Timothy B
Published: December 2024

Background

Hand surgery is commonly required for conditions like Dupuytren’s disease, carpal tunnel syndrome, and carpometacarpal osteoarthritis. Hand experts agree that patient education and managing expectations can optimise surgical outcomes. With an aging population, and rising rates of diabetes and obesity, a significant increase in elective hand surgeries is anticipated over the next decade.

Objective

To assess the effectiveness of preoperative therapy interventions on improving postoperative outcomes following elective hand surgery.

Method

A systematic search of six databases accessed journals from January 2011 to April 2024. Included studies assessed postoperative outcomes following preoperative therapy intervention.

Results

Seven articles met the inclusion criteria: six randomised controlled trials (RCTs) and one retrospective cohort study. Five RCTs explored effects of opioid education on postoperative consumption, all reporting statistically significant differences in favour of the intervention, with one showing a decrease of 49.7 morphine equivalent units (95% CI: 11.9 to 87.5), representing a 34.7% decrease between intervention and control. All RCTs scored poorly for risk of bias with the exception of one which assessed the effects of a neuroscience pain education on postoperative pain, reporting a non-significant decrease of 7.7% favouring the control.

Conclusion

There is a lack of quality research assessing preoperative interventions and outcomes for hand surgery. There was some indication of favourable outcomes following preoperative opioid education; however, number of studies were small, the evidence quality was poor, and data were limited. Further research is required to address these gaps and identify the most effective preoperative interventions.
Context matters: Examining the linguistic aspects of educator-toddler talk
Authors: Zhang Yuxin , Taumoepeau Mele , Reese Elaine
Published: December 2024

The quantity and quality of educator-child talk in early childhood education plays a critical role in children’s language development. This study analysed the linguistic aspects of educator-toddler interactions in 24 New Zealand early childhood classrooms, sampling 25 minutes of naturally occurring interaction across five contexts: book-reading, mealtime, play, group, and nappy-change. Both the quantity (e.g., total utterances) and linguistic quality (e.g., lexical diversity, mean length of utterance in morphemes) of educator and child talk were analysed. The quantity and quality of educator-toddler verbal interactions varied across contexts, with book-reading displaying positive features of educators’ language, and nappy-changes showing positive features of children’s language. This information about which contexts naturally promote high-quality verbal interactions will pave the way for oral language interventions in New Zealand and worldwide.
Clinical Spectrum and Outcome of Kidney Involvement in Non-Langerhans Histiocytosis
Authors: Miao Huilei , Gao Wen , Cao Xinxin
Published: December 2024

Objective: To describe the clinical features and treatment response of Rosai-Dorfman disease (RDD) and Erdheim-Chester disease (ECD) with kidney involvement.

Methods: We conducted a retrospective analysis of patients with RDD and ECD who had kidney involvement between January 2005 and December 2023. We evaluated the kidney response based on kidney function, computed tomography (CT) response and metabolic responses.

Results: A total of 4 RDD patients and 44 ECD patients were included, with a median age of 58 (36-68) and 51(18-66) years, respectively. None of the RDD patients had kidney-associated symptoms, whereas 12 (27.3%) ECD patients presented with lower extremity edema. Regarding baseline kidney function, the median eGFR of RDD and ECD was 80.5 (range: 63-125) and 100 (range: 22-133) ml/min/1.73 m², respectively. Renal mass was the most frequent characteristic of RDD, accounting for 100%, while ECD patients showed a high perirenal infiltration rate (68.2%). Among the 4 RDD patients, one (25.0%) achieved eGFR improvement and two (50.0%) achieved CT response and PET-CT response. In 34 ECD patients evaluable, the percentage of eGFR improvement, CT response and PET-CT response was 14.7%, 5.9% and 52.9%. The median follow-up time was 27.0 months (range: 10.1-52.9 months) for RDD and 53.0 months (range: 3.1-105.3 months) for ECD. The 5-year OS was 66.7% in RDD patients and 81.8% in ECD patients. The median PFS for patients with RDD was 18.3 months, while for those with ECD, it was 59.4 months.

Conclusion: We pioneered the detailed description of kidney involvement characteristics and treatment responses in RDD and ECD. RDD tended to be featured with occupying mass, while ECD is characterized by soft tissue encircling, which is less likely to regress after treatment. Patients with ECD may experience irreversible kidney dysfunction, indicating the critical need for early diagnosis and timely treatment.
A Tumor-Only Whole Genome Sequencing Pipeline for the Development of Molecular Pathology Assays for AML
Authors: Velazquez-Muriel Javier , Tyndale Selene , D'Angelo Julian , Sanchez Paulina , Shah Presha , Huang Ying , Miller Jeffrey E , Niemeijer Meindert
Published: December 2024

Introduction

The discovery of the genomic variants that are part of Acute Myeloid Leukemia (AML) is of great importance for its diagnosis, clinical subtype classifications, treatment, and prognosis. The current state of the art for variant detection utilizes next generation sequencing techniques, typically sequencing only selected regions of the genome involving the most-frequently affected genes (targeted gene panels), or all coding regions. With decreasing costs, the use of whole genome sequencing (WGS) is becoming attractive, as it offers the advantage of uncovering variants outside gene panels or coding regions, a feature of key importance for AML, where structural variants, and in particular gene fusions, are known to play a significant role. We present a tumor-only, somatic WGS pipeline for the development of molecular pathology assays for AML, and potentially, other diseases.

Methods

We built a cloud-based WGS pipeline consisting of 1) sequencing WGS libraries prepared from AML samples using the Illumina DNA Prep workflow on an Illumina NovaSeq 6000 sequencer and S4 flow cell, generating 72-108X coverage per sample, 2) demultiplexing on local hardware to generate sample FASTQ read files, and 3) : read-mapping to the reference genome, quality metrics gathering, deduplication of reads, base quality recalibration, variant calling (single nucleotide variants and small indels), and variant filtering.

We compared the results of our WGS pipeline to those obtained with Invivoscribe's gene panel for 10 clinical samples, 2 AML cell lines (OCI-AML3, MV4-11), and a negative control (HG002). We also ran our WGS pipeline with a reference sample (Seracare Myeloid Mutation DNA mix). In all cases, we looked for detection of the Pathogenic/Likely Pathogenic (P/LP) variants and their variant allele fraction (VAF).

Results

Our WGS pipeline was able to from the reference sample. Compared to MyAML, the WGS pipeline achieved 100% (44/44) detection of the P/LP variants present at for the other samples. Of the 15 P/LP variants with VAF < 5% reported by MyAML, only 1 was detected by the WGS pipeline. The average absolute difference for the VAF value between MyAML and the WGS pipeline was 10% or less for . Our cloud WGS pipeline can process an entire sample from NovaSeq run in 4h or less.

Conclusions

Our WGS pipeline for analyzing WGS data from AML samples can be an effective substitute of the current MyAML gene panel for variants detection with VAF > 5%, . We are working on expanding the capabilities of our current WGS pipeline by adding structural variant calling, variant annotation, and optimization of running times. This proof-of-concept WGS work for AML can be leveraged to develop assays for other diseases with minimal changes in the experimental protocol and bioinformatics analyses.
Clinical Evaluation of Fast-in-Time (FIT) Anti-CD19 CAR T-a Non-Viral, 2-Day Rapid Manufacture CAR T-Cell Therapy for B-Cell Malignancies
Authors: Li Ping , Ge Jian , Ye Shiguang , Zhou Lili , Gong Yiming , Ruan Huaying , Kouros-Mehr Hosein , Liang Aibin
Published: December 2024

Chimeric antigen receptor (CAR) T-cell therapy has shown promise in the treatment of hematologic malignancies, but access barriers exist globally. FIT™, a non-viral, 2-day rapid manufacture autologous CAR T platform, aims to address limitations associated with current CAR T-cell therapies. Here we performed initial clinical evaluation of FIT-CD19-CAR-T, a 2nd generation CD28-CD3ζ CAR T utilizing a humanized anti-CD19 binder.

This investigator-initiated trial evaluated the safety, pharmacokinetics (PK), and preliminary efficacy of FIT-CD19-CAR-T cells in 4 patients (pts) with relapsed or refractory B-cell malignancies, including a B-ALL patient (pt) with 9 prior lines of therapy (LOT) and 50% bone marrow (BM) blasts, a B-ALL pt with 2 LOT and 0.5% BM blasts, an FL pt with 4 LOT and moderate tumor burden (sum of product of diameters [SPD] 3440 mm2) and an FL pt with 2 LOT and 36% BM tumor cells.

CAR T-cells were prepared within 3 days post apheresis. Three pts received 2-3 days of LD chemotherapy (cyclophosphamide 250 mg/m2/day and fludarabine 25 mg/m2/day) begun within 1 day of apheresis at the investigator's discretion and received fresh (non-frozen) FIT-CD19-CAR T-cells with a 5-day vein-to-vein time, while 1 FL is planned to receive cryopreserved CAR T-cells as per his willingness. Two ALL pts received 70k and 100k CAR-T cells/kg, while the FL pt received 600k CAR T-cells/kg. Peak CAR T-cell copy numbers were comparable to approved CD19 CAR T-cell products with Cmax occurring on days 13-14 after CAR T treatment. Overall, the treatment exhibited an acceptable safety profile with manageable cytokine release syndrome (CRS; G3 and G2 in ALL pts; no CRS in FL pt) and immune effector cell-associated neurotoxicity syndrome (ICANS; 1 case of G3 in ALL patient). All three evaluable pts have achieved complete remission as their best objective response, with ongoing MRD-negative CR for over 4 months and 6 months in the two ALL pts. One FL pt experienced disease progression at the 6-month assessment due to newly developed cervical lesions, while the original lesions continued to show ongoing metabolic remission.

In conclusion, FIT-CD19-CAR-T demonstrates a favorable safety profile and encouraging initial efficacy and PK at relative low doses in pts with heavily pretreated B-cell malignancies, which may be attributable to enhanced expression of naïve and stem cell memory markers on rapidly manufactured FIT-CD19-CAR-T cells that were not expanded or activated ex vivo. Phase 1 studies are planned for continued investigation.
Modulating Schlafen 12 Activity Using Velcrins in Acute Myeloid Leukemia Cells
Authors: Guillen Magana Jamie Nelly , Platanias Leonidas C. , Zannikou Markella , Small Sara H. , Baran Aneta H. , Beauchamp Elspeth M. , Eckerdt Frank Dieter
Published: December 2024

Schlafen 12 (SLFN12) belongs to the Schlafen (SLFN) family of proteins, classified as

interferon-stimulated genes with diverse biological functions. In humans, SLFNs exert a role via

their endonuclease and/or helicase domains in cellular proliferation, differentiation, immune

responses, and chemosensitivity of malignant cells. Accumulating evidence suggests that SLFN

family members could serve as prognostic markers in certain malignancies and may be

potential novel therapeutic targets. Using data from the TCGA database, we found that SLFN12

is notably overexpressed in acute myeloid leukemia (AML). To modulate SLFN12 activity in

AML cell lines, we utilized velcrins. Velcrins are a class of molecular glues that facilitate

heterotetramer formation between SLFN12 and phosphodiesterase 3A (PDE3A). This stabilizes

SLFN12 protein and enhances its RNAse activity, ultimately inducing cancer cell death. Velcrins

effectively reduced cell viability and leukemic progenitor potential in colony forming assays in

AML cell lines, with particular sensitivity observed in HEL cells characterized by elevated

SLFN12 and PDE3A levels. Further investigation revealed that velcrin treatment promoted the

SLFN12-PDE3A interaction and potently induced apoptosis in AML cell lines. In cell lines with

lower PDE3A levels, PDE3B, an isoform of PDE3, seems to be partially mediating velcrin

sensitivity as co-immunoprecipitation analysis confirmed a PDE3B-SLFN12 protein interaction

following velcrin treatment in U937 cells, which do not express PDE3A. Moreover, in vivo

experiments utilizing HEL subcutaneous xenografts, demonstrated significant reduction in tumor

burden and prolonged survival upon velcrin treatment, further supporting its therapeutic efficacy

in AML. We also demonstrated enhanced effects in vitro when combined with azacitidine in the

reduction of leukemic cell viability. Altogether, these findings demonstrate an important role for

SLFN12 in AML and raise the potential of velcrins as agents with unique activity in the

treatment of AML.
Co-Concurrent Protein C Deficiency and Myocardial Infarction: A Case Report and Systematic Review
Authors: Kanitthamniyom Chanakarn , Rungjirajittranon Tarinee , Owattanapanich Weerapat
Published: December 2024

Introduction:

The association between arterial thrombosis and protein C (PC) deficiency has not been well-studied. Previous Systematic reviews and meta-analyses have shown a two-fold increase in ischemic stroke incidence among PC-deficient patients compared to controls. However, data on myocardial infarction (MI) is limited.

Objective:

This study reports a case of MI in a patient with PC deficiency and performs a systematic review to characterize MI presentations, PC deficiency details, and treatments in affected patients.

Methods:

We conducted a descriptive review of case reports on PC deficiency and MI. Studies published before June 2024 were searched in Ovid MEDLINE and EMBASE by three investigators.

Results:

We included 33 patients, including our case. The median age was 37 years (IQR, 26.5-44 years). Six patients (18.2%) had additional atherosclerotic risk factors. Notably, 57.6% (19 patients) had recurrent thrombotic events, both arterial and venous. Median PC activity was 42.8% (IQR 32.3-50.5%), and median PC antigen level was 44% (IQR 39.7-52.2%). Four genetic mutations in the PROC gene were identified: c.325G>A (p.G109R), c.764T>A (p.M255L), c.577_579delAAG (p.192delK), and c.565C>T (p.R189W). Coronary angiography frequently showed total occlusion by thrombus without obvious atherosclerosis. Most patients were treated with oral anticoagulants and anti-platelet therapies.

Conclusions:

This study suggests a potential association between PC deficiency and MI, with recurrent thrombotic events in some patients. These findings highlight the need to consider PC deficiency in MI diagnosis, especially when coronary angiography shows no atherosclerotic disease. Further research is needed to clarify this association.
Retrospective Analysis of 118 Cases of Primary Central Nervous System Lymphoma
Authors: Wu Shaojie , Deng Yanni , Lai Mingyao , Tu Sanfang , Cai Linbo , Li Yuhua
Published: December 2024

Purpose: To retrospectively analyze the clinical efficacy of high-dose methotrexate (HD-MTX)-based regimens in treating primary central nervous system lymphoma (PCNSL), and to evaluate the impact of autologous hematopoietic stem cell transplantation (AHSCT) or maintenance therapy on long-term survival of patients.

Methods: A total of 118 PCNSL patients treated between January 2016 and December 2023 were included. They were classified into 5 groups based on treatment regimens: single-agent (HD-MTX), two-drug(HD-MTX and temozolomide), three-drug (rituximab, HD-MTX and temozolomide or radiation), four-drug (rituximab, HD-MTX, temozolomide and BTKi), and radiation alone. The number of cases in each group was as follows:17, 18, 39, 20,and 24,respectively. Clinical efficacy and adverse events among these groups were analyzed.

Results: The median follow-up time for the 118 PCNSL patients was 45 months. The median overall survival (OS) was 25 months, and the median progression-free survival (PFS) was 20 months. Subgroup analysis revealed that patients in the four-drug regimen group had significantly higher OS and PFS compared to the other four groups (P values of 0.045 and 0.036, respectively). Additionally, patients in the four-drug group had a significantly higher objective response rate (ORR) after two cycles compared to the other groups (P=0.026). Further analysis demonstrated a trend towards improved OS (P=0.077) and PFS (P=0.067) in the group receiving BTKi-containing regimens. After induction chemotherapy followed by sequential AHSCT or maintenance therapy, the median OS was 25 months and median PFS was 20 months for both the AHSCT group and the maintenance therapy group. Both OS in the maintenance therapy and AHSCT groups were significantly higher than those in the observation group (P values of 0.037 and 0.039, respectively).Similarly, PFS was superior in both the maintenance therapy group and the AHSCT group compared to the observation group (P values were 0.017 and 0.062, respectively). Hematologic toxicity was observed in 53.4% (63/118) of patients, all graded as CTCAE 1-2. Non-hematologic toxicities, mainly nausea, vomiting, and mucositis, were also graded as 1-2 and did not lead to any toxicity-related death.

Conclusion: The use of four-drug regimens based on HD-MTX shows significant efficacy in the treatment of PCNSL, with a higher ORR after two cycles. Post-induction strategies with AHSCT or maintenance therapy further improve treatment efficacy. In addition, regimens containing BTKi indicate a potential benefit in long-term survival, which warrants further investigation.
Combined Natural Language Processing and Gpt-4 Pathology Report Interpretation Efficiently Identify a Myelodysplastic Syndrome Cohort for Large Scale Clinical Research Applications
Authors: Gracie Thomas J. , Pershad Yash , Bejan Cosmin , Bick Alexander G. , Ferrell Brent , Kishtagari Ashwin
Published: December 2024

Introduction

Cohort studies provide a unique opportunity to test hypotheses that cannot be evaluated through randomized controlled trials. To be effective, they require a substantial and carefully chosen cohort, which typically necessitates time-consuming doctor chart reviews. Some Electronic Health Record (EHR) compatible automation strategies have been designed to speed up this process. However, these are often ineffective for diseases diagnosed through pathology, such as Myelodysplastic Syndrome (MDS), due to the storage of clinical pathology data in free-text reports. In this study, we used a combination of natural-language processing (NLP), International Classification of Diseases (ICD) coding, and Generative Pre-trained Transformer 4 (GPT-4) free-text analysis to sift through a large clinical database and identify patients with pathology-confirmed MDS that met several additional criteria.

Methods

We used the Research Derivative (RD), a clinically annotated database at VUMC, to screen for patients with MDS-related ICD-10 codes, available sequencing data, and hematopathology keywords identified through NLP. Out of 5 million patients, 724 met these criteria. We then used GPT-4 to analyze the pathology reports from their diagnostic bone marrow biopsies. The model provided a certainty score between 0 and 1 for the usability of each report, with 1 representing 100% certainty. The usability of a report was defined by three criteria: it was a bone marrow biopsy report diagnostic of MDS; it showed no evidence of any other hematologic disease; and it did not mention any prior MDS treatment. We used these scores to generate a Receiver Operating Characteristic (ROC) curve, which helped us determine the best threshold for converting usability scores into a simple ‘yes’ or ‘no’. We then compared these results with manual chart reviews for verification.

Results

The area under the ROC was 0.95, with the optimal threshold for classification at a usability score of 0.5. Using this threshold, the GPT model achieved a recall of 0.981, incorrectly excluding only one case out of the 724 patients that met the NLP and ICD10 criteria. The accuracy was 0.756, with the most common reason for inaccuracy being the absence of pretreatment information in the hematopathology report. This was confirmed through manual chart reviews.

Conclusions

The combination of NLP, ICD coding, and GPT-4 analysis proved highly effective in screening a large clinical database for patients with pathology-confirmed MDS, reducing potential study candidates from five million to several hundred. Manual reviews of separate clinical charts revealed treatment status information not listed in the pathology reports. Future automated phenotyping efforts could benefit from GPT-4 screening of contemporaneous clinic notes to enhance precision.
Ultrasound Exhibited Superior Advantages over 18F-FDG PET/CT in Monitoring Follow-up of DLBCL
Authors: Hanzhen Zhang , Wei Yongqiang , Wei Xiaolei , Feng Ru
Published: December 2024

Purpose: The purpose of this study was to comparison of Ultrasound and 18F-FDG PET/CT for finding refractory/relapse DLBCL after first-line therapy.

Methods: From January 2012 to September 2023, newly diagnosed DLBCL patients in our center who underwent standard first-line treatment and had complete follow-up records after treatment were enrolled. Data regarding patients' clinical and imaging data, as well as their therapeutic responses were collected.

Results: A total of 597 patients was analyzed, including 146 patients with refractory/relapse DLBCL. Among the 146 cases, there were 49 patients presented with signs and symptoms of relapse. 97 patients showed recurrence on imaging follow-up without abnormal signs or symptoms, 93 of these patients was detected by ultrasound, 52 of these were also confirmed through 18F-FDG PET/CT imaging and 41patients did not undergo 18F-FDG PET/CT due to economic constraints, intolerance, or other factors. 18F-FDG PET/CT indicated recurrence despite normal ultrasound imaging in two patients, one patient had mesenteric lymph node recurrence, another one patient had intravertebral recurrence. CT indicated recurrence despite normal PET/CT imaging in two patients.

Conclusions: Ultrasound identified most of asymptomatic DLBCL patients with relapse. However, the application of PET/CT is limited due to its high cost and radiation characteristics. Therefore, it is recommended that ultrasound be used as a routine follow-up examination for DLBCL.
Protein Energy Malnutrition and in-Hospital Outcomes Among Hospitalized Patients with Immune Thrombocytopenia: A United States Collaborative Network Cohort Study
Authors: Jones Colton Frisco , Obomanu Elvis , Verinumbe Tarfa , Elom Hilary A , Yusuf Hasiya , Byfield Karecia , Ugwe Chidiebube , Arya Yajur , Syal Arshi , Mayo Ryan J
Published: December 2024

Background

Immune thrombocytopenia (ITP) is an acquired form of thrombocytopenia seen in adults and children. It is characterized by immune-mediated platelet destruction and can lead to life-threatening bleeding in certain patients. Protein-energy malnutrition (PEM) can lead to adverse outcomes in many medical conditions; however, whether its presence leads to adverse outcomes in patients with ITP is yet to be determined.

Methodology

We conducted a secondary analysis of data from the United States Collaborative Network-TriNetX. Our study sample included patients with ITP [defined based on the International Classification of Disease, 10th Revision (ICD-10) code (D69.3)]. PEM was our primary exposure (determined based on the ICD-10 code E46). ITP patients with and without PEM were propensity-matched to ensure both groups had similar sociodemographic characteristics. Clinical outcomes assessed were hospital readmission, intensive care unit (ICU) admission, recurrent bleeding, need for transfusion, risk of myocardial infarction (MI) and pulmonary embolism (PE), and all-cause mortality. Generalized linear models were used to measure the association of PEM and the clinical outcomes of interest. Estimates were presented as risk ratios and 95% confidence intervals, and a p-value of <0.05 was considered statistically significant.

Results

After propensity score matching, 4607 participants were included in each cohort. In the PEM cohort, 46% were male, 64%% were white, and the mean age was 64.8 years (SD +/- 20.2). About 76% had hospital readmission, 30% had an ICU admission, 13% experienced recurrent bleeding, 15% needed transfusion, 6% had MI and PE, and all-cause mortality was 32% in the PEM cohort. Participants admitted with ITP and concurrent PEM had a statistically significant higher risk of hospital readmission (RR 1.329, 95% CI: 1.290-1.369), ICU admission (RR 2.153, 95% CI: 1.980-2.341), recurrent bleeding (RR 1.145, 95% CI: 1.026-1.278), need for transfusion (RR 1.640, 95% CI 1.423-1.889), risk of MI and PE (RR 1.507, 95% CI 1.226-1.852), and risk of all-cause mortality (RR 1.905, 95% CI 1.764-2.056) when compared to those without PEM.

Conclusion

Our study found a considerable proportion of patients with ITP and comorbid PEM. Findings suggest that ITP patients with concurrent PEM are at a higher risk of adverse health outcomes and mortality than ITP patients without PEM. Early recognition and prompt management of PEM among patients with ITP may contribute to improved clinical outcomes.
Gender Influences Epidemiologic Characteristics of Secondary Malignant Neoplasms in Classical Ph Negative Myeloproliferative Neoplasms
Authors: Cai Yanan , Wang Yuebo , Lu Wenyi , Zhang Ping , Zhu Zunmin
Published: December 2024

Objectives:

To explore the influence of gender on the incidence of secondary malignant neoplasms (SMNs) among patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), based on The Surveillance, Epidemiology and End Results (SEER).

Methods:

We used the ICD (International Classification of Diseases) for Oncology, third edition (codes 9950, 9961, and 9962) to assemble a retrospective cohort of patients with PV, ET and PMF diagnosed between 2000 and 2018 in SEER 18. SMNs were defined as new cancer diagnoses occurring in patients with diagnosis of PV, ET and PMF at least 6 months prior to the diagnosis of a new malignancy. Other exclusion criteria included unknown age and diagnosis by autopsy or death certificate only.

Results:

The cohorts enrolled 35645 patients with myeloproliferative neoplasms (MPNs), including 17416 male patients (48.9%) and 18229 female patients (51.1%). The incidence of SMNs in male patients was higher than female patients (11.7% versus 9.1%，P＜0.001). This trend was also observed across PV,ET and PMF patients (11.4% versus 9.8%, 12.6% versus 8.7%, 10.9% versus 8.3% respectively，all P value＜0.05). The median time from diagnosis of MPNs to SMNs in male and female patients were similar [48 (6-217) versus 49.5 (6-207) months, P=0.884]. In subgroup analysis, the median time from diagnosis of PV and ET to SMNs in male patients were 54 (6-200) and 50.5 (6-207) months respectively, similar to those in female patients [54 (6-227) and 49 (6-201) months with P=0.994 and 0.645, respectively]. However, the median time from diagnosis of PMF to SMNs in male patients was shortened when compared with female patients [30(6-159) versus 38 (7-186) months, P=0.046]. In terms of the spectrum of SMNs, the most common site of non-hematological solid SMNs in male patients were prostate (2.5%), lung (1.5%), skin (0.7%), bladder (0.5%), gastrointestinal (0.4%) and kidney (0.4%), while breast (1.5%), lung (1.2%), reproductive system (0.5%), skin (0.3%), gastrointestinal (0.3%), kidney (0.3%) and thyroid (0.2%) cancers dominated the top of non-hematological solid SMNs in female patients. Survival analysis showed that the cumulative incidence of SMNs, leukemia, non-leukemic hematological cancers (including myelodysplastic syndromes and lymphoma) and solid SMNs were similar between male and female patients with PV and ET (all P value＞0.05). However, male patients with PMF suffered higher incidence of SMNs and leukemia than female patients with PMF (P=0.002 and 0.005, respectively), but the cumulative incidence of non-leukemic hematological cancers and solid SMNs in male PMF patients did not differ with female PMF patients (P=0.52 and 0.081, respectively).

Conclusion:

Gender influences incidence and spectrum of SMNs in MPNs. Male patients with PMF developed SMNs earlier and suffered higher incidence of SMNs, especially leukemia, over time.
Epidemiology and Survival Outcomes of Acute Promyelocytic Leukemia in Adults: A SEER Database Analysis
Authors: Ali Hassan , Durugu Satya R , Agrawal Shubham , Sinha Shrishti , Santhi Jaison Lawrence Alexander , Bodrova Elizaveta , Ahmed Aftab , Bajwa Shammas , Bajwa Umair , Faisal Muhammad Salman , Thirumaran Rajesh
Published: December 2024

Background:

Acute Promyelocytic Leukemia (APL) is a relatively uncommon and highly aggressive variant of Acute Myeloid Leukemia, also known as AML-M3. Characterized by the classic translocation t(15;17) and hence retinoic acid receptor (RAR) disruption, APL leads to accumulation of numerous immature blasts in the bone marrow. APL is notorious for causing distinctive and fatal coagulopathy due to the presence of Auer Rods. Pancytopenias with associated sequelae are frequently present. With the advent of all-trans retinoic acid (ATRA), APL has transformed from highly lethal disease to a curable neoplasm with a remission rate of over 90%. ATRA in combination with anthracycline-based chemotherapy is widely used. Newer trails with ATRA/ATO (arsenic trioxide) combination have also shown promising results. We aim to determine survival outcomes for APL based on various demographic factors.

Method:

We extracted 5403 cases of acute promyelocytic leukemia diagnosed after the age of 18 years, using the ICD Code 9866/3, from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2023 Sub (2000-2021). Data was stratified based on age, gender, race, median household income inflation adjusted to 2022 and chemotherapy-based treatment regimen. Results were compared using Log-Rank test (GraphPad Prism).

Results:

Of the reported cases, APL was equally distributed among males and females. The median age of diagnosis was 51 years. Most of the cases were reported in Caucasians (57.34%), followed by Hispanics (22.75%), Blacks (10.6%), Asian/Pacific Islanders (8.4%), Alaskan/Native Americans (0.54%) and non-Hispanics of unknown race (0.4%). The Median of survival (MoS) calculated for females was 240 and males was 219 (p 0.0045). Survival based on age showed drastic decline as the age advanced (p <0.0001). Survival obtained for race was undefined for Asian/Pacific Islanders and Hispanics likely for insignificant numbers of death events, while 203 months for White (p <0.0001). Analysis based on chemotherapy showed statistically significant improvement in survival (p <0.0001). Comparison of the curves with reference to median household income revealed higher MoS with increasing income bracket (p 0.0183).

Conclusion:

Acute Promyelocytic Leukemia is a rare and belligerent subtype of AML. Distribution is gender unbiased, but frequently affects Caucasians and Hispanics. Female gender, younger age, Asian/Pacific Islander/Hispanic race, chemotherapy and higher income bracket (>100K) are associated with improved outcomes. The rarity of this neoplasm requires more research and analysis to better understand its nature.
Clinical and Molecular Predictors of Response and Survival Following Venetoclax Plus Hypomethylating Agents in Relapsed/Refractory Acute Myeloid Leukemia
Authors: Wang Lin-Ya , Tang Feifei , Huang Xiao-Jun , Gao Hai-Tao , Fu Qiang , Jiang Qian , Jiang Hao , Wang Yu , Xu Lan-Ping , Zhang Xiaohui
Published: December 2024

This study aimed to investigate the efficacy and the clinical and molecular predictors of response and survival following venetoclax plus hypomethylating agents (VEN+HMAs) in relapsed/refractory acute myeloid leukemia (R/R AML) patients. We retrospectively analyzed 197 R/R AML patients with next-generation sequencing (NGS) treated with VEN+HMAs regimen. The median treatment cycle was 1 (1-4) cycle. Composite complete remission (CRc) including the complete remission (CR) plus CR with incomplete hematologic recovery (CRi) rate was 44.7%, and the overall response rate (ORR) was 59.9%. The median follow-up was 14.0 (0.7- 54.0) months, 1- year and 2- year overall survival (OS) was 55.4% and 40.2%, respectively. Mutations in NPM1 and SRSF2 were favorable factors for response (Odds Ratio (OR) 2.3, P = 0.008; OR 2.5, P = 0.036, respectively). Prior HMA, early relapse and GATA2 mutation were unfavorable factors for response [OR 0.4, P = 0.006; OR 0.4, P = 0.021; OR 0.1, P = 0.005, respectively]. For survival, mutations in NPM1 and IDH1/2 were the protective factors for OS; mutations in FLT3-ITD, TP53, DNMT3A and GATA2 were the risk factors for OS. In conclusion, VEN+HMAs regimen was effective for R/R AML patients, and the treatment response and OS were associated with genetic characteristics.