bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eosinophilic pericardial effusion and pericarditis in a cat
Authors: Wheatley Meagan Alisa , Shamoun John , Maggi Ricardo , Breitschwerdt Edward B , Sommer Samantha L , Cullen John M , Stowe Devorah Marks 
Published: December 2023

Case summary A 10-year-old domestic shorthair cat presented for lethargy, anorexia and labored breathing. Significant pleural and pericardial effusions prompted thoracocentesis and pericardiocentesis. Cytologic evaluation of the pericardial effusion revealed a highly cellular hemorrhagic, eosinophilic (12%) effusion, with many markedly atypical suspected mesothelial cells, interpreted as concerning for neoplasia. Thoracoscopic subtotal pericardiectomy and histology of the pericardium revealed predominantly eosinophilic inflammation with multifocal mesothelial hypertrophy and ulceration. A peripheral eosinophilia was not present on serial complete blood counts. Initial infectious disease testing was mostly negative. Toxoplasma gondii titers were most consistent with prior exposure, although reactivation could not be excluded. The owner’s medical history included a prior diagnosis of bartonellosis. Owing to the challenges of definitive Bartonella species exclusion, the cat was treated empirically with pradofloxacin and doxycycline, and a subtotal pericardectomy. There was improvement at first but pleural effusion recurred approximately 3 months after discharge. The cat was euthanized and a necropsy was not performed. Subsequent pericardial effusion Piroplasma/Bartonella/Borrelia droplet digital PCR detected DNA of Bartonella vinsonii subspecies berkhoffii, and peripheral blood culture and sequencing revealed a rare apicomplexan organism (90% homology with Colpodella species) of unknown clinical significance. Testing for filamentous bacteria and fungal pathogens was not performed. Relevance and novel information This case offers several unique entities – eosinophilic pericardial effusion and eosinophilic pericarditis of unknown etiology – and illustrates the well-known marked atypia that may occur in reactive and hyperplastic mesothelial cells, particularly of infrequently sampled and cytologically described feline pericardial effusion, supporting a cautious interpretation of this cytology finding.
Identifying Discrepancies in Gestational Diabetes Mellitus Postpartum Follow-Up During Care Transitions
Authors: Strelow Brittany , Herndon Justine , Ferrier Alex , McCormick Madysen , McMahon AnneMarie , Schlechtinger Emily , Shefa Deborah , Takagi Mark , McCoy Rozalina , Olson Rachel , O’Laughlin Danielle 
Published: December 2023

Background: Gestational diabetes mellitus (GDM) is a common complication of pregnancy that carries lasting risks. For women who have a history of GDM, the risk of developing type 2 diabetes mellitus (T2DM) increases by 50 to 60%. To monitor and prevent the development of T2DM, guidelines suggest screening those with a history of GDM at 6-weeks and 3-years post-delivery. For patients with abnormal lab results at the 6-week mark, it is advised to complete lab work sooner, at the 1-year mark. Data suggests that these guidelines are not being followed globally, and most do not receive adequate screening for T2DM. Methods: A retroactive chart review of 203 women between 18 and 55 years old with a past medical history significant for GDM was conducted to determine if patients with GDM completed screening for T2DM at 6-week, 1-year, and 3-year timestamps post-delivery. Patient demographics (age, race, ethnicity, language), clinical characteristics (body mass index), provider gender, and whether prediabetes or T2DM developed were recorded. Patients who did not complete the required follow-up received educational materials via the online portal system, and hemoglobin A1c (HbA1c) screening tests were ordered. Results: Ninety days post-intervention, 38 patients (50%) completed the HbA1c screening test, which exceeded our goal of a 5% improvement. Age and BMI 1-year postpartum were found to be significant factors in whether a patient completed HbA1c screening, with 16/18 (89%) completing screening with a healthy BMI 1-year postpartum (18.5 ≤ BMI < 25.0) but only 11/41 (27%) completing screening for patients under 40 years with an unhealthy BMI 1-year postpartum. Of the 38 patients who completed HbA1c screening, 9 (23.7%) had abnormal screening results. Conclusion: Follow-up surveillance for T2DM among women with a history of GDM is poor. Electronic health records can be used to identify and rectify gaps in care. Dissemination of standardized educational materials and electronic order entry for patients improved screening between the handoff from obstetrics to primary care.
Challenging Interactions Between Patients With Severe Health Anxiety and the Healthcare System: A Qualitative Investigation
Authors: Brady Robert E. , Braz Armando N. 
Published: December 2023

Objective: Patients with severe health anxiety have complex interpersonal relationships with medical providers and others in their social context, often resulting in conflictual interactions with providers and perception of poor medical care. An adequate understanding of the causes and consequences of these interactions is lacking, particularly 1 informed by the experience of the patient. This study used qualitative methods to explore the development and maintenance of health anxiety from the perspective of patients with lived experience of coping with health anxiety and their interactions with the healthcare system. Method: We conducted qualitative interviews with 11 primary care patients purposely sampled to describe their experience living with health anxiety, provider interactions, and social and family interactions surrounding health and health anxiety. We extracted themes related to living with health anxiety and interactions with providers and other significant relationships. Results: Thematic content analysis revealed 5 themes including 3 causal themes, 1 response theme, and 1 theme reflecting factors that mitigate health anxiety. Causal themes included subthemes reflecting predisposing factors of the self, key stimulus events from patient learning history, and maladaptive social interaction factors. The response theme was comprised of 2 subthemes: logical conclusions and health anxiety symptoms. The mitigating factors theme included subthemes of a trusting care relationship and recognition of disconfirming evidence. Conclusion: The themes and constituent subthemes identified in this study largely map onto cognitive-behavioral theory of health anxiety, demonstrating alignment between patient experience and theory. The resulting model also identifies potential points of intervention in the developmental and maintenance process. We provide recommendations to maximize those points of intervention.
A Telemedicine Center Reduces the Comprehensive Carbon Footprint in Primary Care: A Monocenter, Retrospective Study
Authors: Schmitz-Grosz Krisztina , Sommer-Meyer Carsten , Berninger Philipp , Weiszflog Elsa , Jungmichel Norbert , Feierabend David , Battegay Edouard 
Published: December 2023

Introduction: Telemedicine reduces greenhouse gas emissions (CO2eq); however, results of studies vary extremely in dependence of the setting. This is the first study to focus on effects of telemedicine on CO2 imprint of primary care. Methods: We conducted a comprehensive retrospective study to analyze total CO2eq emissions of kilometers (km) saved by telemedical consultations. We categorized prevented and provoked patient journeys, including pharmacy visits. We calculated CO2eq emission savings through primary care telemedical consultations in comparison to those that would have occurred without telemedicine. We used the comprehensive footprint approach, including all telemedical cases and the CO2eq emissions by the telemedicine center infrastructure. In order to determine the net ratio of CO2eq emissions avoided by the telemedical center, we calculated the emissions associated with the provision of telemedical consultations (including also the total consumption of physicians’ workstations) and subtracted them from the total of avoided CO2eq emissions. Furthermore, we also considered patient cases in our calculation that needed to have an in-person visit after the telemedical consultation. We calculated the savings taking into account the source of the consumed energy (renewable or not). Results: 433 890 telemedical consultations overall helped save 1 800 391 km in travel. On average, 1 telemedical consultation saved 4.15 km of individual transport and consumed 0.15 kWh. We detected savings in almost every cluster of patients. After subtracting the CO2eq emissions caused by the telemedical center, the data reveal savings of 247.1 net tons of CO2eq emissions in total and of 0.57 kg CO2eq per telemedical consultation. The comprehensive footprint approach thus indicated a reduced footprint due to telemedicine in primary care. Discussion: Integrating a telemedical center into the health care system reduces the CO2 footprint of primary care medicine; this is true even in a densely populated country with little use of cars like Switzerland. The insight of this study complements previous studies that focused on narrower aspects of telemedical consultations.
Machine Learning Models for Hematogone Enumeration and Differentiation between Hematogones and Leukemic-Blasts in B-Acute Lymphoblastic Leukemias
Authors: Liu Xiaolong Sean 
Published: December 2023

Background:
Hematogone (htg) counts are usually low in bone marrows but often increase in reactive or neoplastic conditions. When increased, htgs resemble leukemic-blasts in B-lymphoblastic leukemias (B-ALL) phenotypically. The differentiation between htgs and leukemic-blasts is critical as hematogone counts in marrows with reactive conditions may increase around or beyond B-ALL leukemic-blast diagnostic level and, conversely, leukemic-blast counts may be low in some B-ALL marrow samples. Additionally, current hematogone enumeration by the gating approach is operator dependent.
Objective:
To enumerate htgs and differentiate htgs from leukemic-blasts using machine-learning (ML) models.
Research Methods:
Cases with reported htgs (CReH), B-ALL, and controls (548, 124, and 771 marrow samples, respectively) were selected using key word search from historical flow cytometry (FC) results. Datasets for analysis were from FC-panel: FS_SS_CD5_CD10_CD20_ CD19_CD45.
Three preliminary models, the htg enumeration model (HEM), immature cell enumeration models for B-lineage (IEM_B), and htg similarity model (HSM), were used (data not published). HSM classified a given htg-population or leukemic-blast-population into three categories: Htg-p (htg-population), Borderline, and non-Htg-p.
Results:
HEM distinguished CReHs with median 530 from the controls with median 5 (figure 1). Only six (&lt;1%) of the controls had &gt;500 htgs.
IEM_B was used for separating hgt-populations in CReHs or leukemic-blast-populations in B-ALL cases from other cell populations. HSM classified 100 (95.2%) out of 105 hgt-populations from CReHs (≥1000 htgs) as Htg-p, and, due to fluorescence intensity downward shift, 4 as non-Hgt-p and 1 as Borderline. Conversely, HSM classified 113(92%) out of 123 leukemic-blast-populations from B-ALL as non-Hgt-p, 6 (5%) as Hgt-p and 4 (3%) as Borderline. Multiple scatter plots (figure 1a) illustrate two-dimensional distributions of a leukemic cluster classified as non-Hgt-p in a B-ALL case compared with those of a standard hematogone cluster.
Conclusion:
In an experimental setting, HEM is an efficient/high-throughput alternative for hgt-enumeration with high-consistency and is operator-independent. In the majority of B_ALL cases, HSM was able to differentiate leukemic-blast-populations from htg-populations. Future models will use additional markers, including leukemia-specific ones, to increase models' specificity.
Efficacy and Safety of Single Versus Tandem Autologous Stem Cell Transplantation in Multiple Myeloma: A Single-Center Retrospective Analysis in China
Authors: Qiu Zongjian , Li Xiaofan , Zhan Rong , Li Nainong 
Published: December 2023

Background: Currently, there is a lack of comparative data on the efficacy and safety of single or tandem ASCT in China. This study aimed to review the efficacy and safety of single or tandem ASCT in MM patients without selection criteria for specific studies.
Methods: Utilizing matched case-control study, we retrospectively analyzed the clinical data of 80 newly diagnosed MM (NDMM) patients who underwent ASCT in our department between November 2014 and June 2021, with 40 patients in each group receiving either single or tandem ASCT.
Results: In single ASCT group, the percentage of ≥CR before or post ASCT was 50% and 70%, respectively. In tandem ASCT group, the percentage of ≥CR pre ASCT was 47.5%, while the percentage of ≥CR after 1 st and 2 nd ASCT was 65% and 85%, respectively. From 1 st transplantation, the median progression-free survival (PFS) was 33.2 and 71.1 months for the single and tandem arm, respectively (P=0.0099), and the median overall survival (OS) for the single and tandem arm was 38.3 and 75.8 months, respectively (P=0.0519). In the single and tandem group, 7-year PFS was 29.9% and 57.0%, while 7-year OS was 26.3% and 43.5%, respectively. The median PFS was 23.2 and 61.2 months for the single and tandem arm in patients with high risk (P=0.038), while the median OS was 32.4 months and 65.8 months, respectively (P=0.045). No transplant-related mortality occurred in both cohorts. The median times to neutrophil and platelet engraftment for single group were 11 days and 13 days, respectively. In the tandem group, the median times to neutrophil engraftment post 1 st and 2 nd transplantations were 11 days and 12 days, respectively, while the mean engraftment times for platelets were 12 days and 17 days. Mucositis, engraftment syndrome, and infection were common but manageable complications.
Conclusion: Upfront tandem ASCT could deepen the depth of response and prolong PFS in MM patients and could be performed feasibly and safely in patients with myeloma, especially when novel agents are not available in China.
Identification of HLA Class I Alleles in Patients with Paroxysmal Nocturnal Hemoglobinuria with Different Clone Sizes
Authors: Zhang Zhuxin , Hu Qinglin , Zhuang Junling , Han Bing 
Published: December 2023

Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is a hematological disease characterized by complement-mediated hemolysis, thrombosis, and bone marrow failure. Human leukocyte antigen (HLA) evolutionary divergence and mutations were widely analyzed in aplastic anemia (AA). However, there were few studies in PNH thus far.
Methods Patients with newly diagnosed PNH at Peking Union Medical College Hospital (PUMCH) were recruited from April 2019 to April 2021 according to International PNH Interest Group standards. They were analyzed the genotypes of classical HLA class I loci (A, B, C) using whole-exome sequencing (WES). Patients were further stratified into four groups according to the clone size (Group A: &lt;10%; Group B: 10% ≤ to ≤50%; Group C: 50% &lt; to ≤80%; Group D: &gt;80%) to identify the association between HLA class I alleles and PNH clone size.
Result Samples from 40 patients were enrolled, including 20 classic PNH and 20 bone marrow failure (BMF)/PNH. There were 29 males and 11 females. The median age was 32 years (range, 16-70). The median PNH clone size measured by flaer-granulocyte ratio was 72% (range 1-99%). Among the 59 identified alleles in PNH, HLA-B genotypes, which were reported to be associated with severe AA, accounted for the highest percentage (46%). A*02:01, the most common one and found in all the four groups, was reported as one of the risk alleles overrepresents in AA. The alleles found in group A were significantly different from those in group B, C, and D ( P = 0.004, 0.006, and &lt; 0.001, respectively). But there was no significant difference between B, C, and D groups ( P &gt; 0.05). 47% of the alleles identified in group A were reported in AA, whereas only 26%, 23%, and 26% of the detected alleles in Group B, C, and D were reported in AA, respectively. The other alleles in B, C, D groups were mainly for the susceptibility of autoimmune diseases or drug-related adverse reactions. Among them, HLA-B*46:01, the most common and found in B, C and D groups, may indicate weak antigen presentation and immune ability. B*44, B*57:01, C*07:01 were unique in Group B, B*38:02 were identified in Group C and HLA-B*27 expressed most in Group D, which were mainly on cell survival, drug hypersensitivity, and complement activation.
Conclusion
Significantly different alleles were observed between PNH with smaller clone sizes (&lt; 10%) and PNH with larger clone sizes (≥10%). Patients with smaller clone sizes had similar HLA class Ⅰ alleles to AA; whereas those with larger clone sizes had numerous unique alleles which may contribute to the pathogenesis of PNH.
Keywords: paroxysmal nocturnal hemoglobinuria, human leukocyte antigens, clone size, class I allele, pathogenesis
Efficacy Evaluation of a Tetracyclic Triterpene Compound Targeting Multiple Apoptosis Proteins for the Development of a Multiple Myeloma Treatment
Authors: Kim Hye Ran , Lee Young Eun , Lim Ha Jin , Choi Yong Jun , Park Joo Heon , Shin Jong Hee , Park Chang Soo , Shin Myung Geun 
Published: December 2023

Introduction:Multiple myeloma (MM) is an incurable hematologic cancer that originates in plasma cells and occurs primarily in older patients over 60. This study screened for hit compounds for MM treatments targeting mitochondria and apoptosis proteins. Further, non-clinical testing, including molecular docking analysis, was performed.
Methods: Based on our previous studies, candidate compounds targeting mitochondria were screened (www.medchemexpress.com). The killing effect of the compounds on MM cell lines (RPMI8226, IM9, and U266) was examined using a sulforhodamine B assay. Apoptosis mechanisms were investigated in vitro. Complex immunocompromised mice were established by injecting RPMI8226-RFP-FLuc cells through the tail vein. Efficacy of the KBB-N2 activity was assessed following intraperitoneal (15 or 30 mg/kg/day) and tail vein (7 mg/kg/day) infusions for three days a week at daily intervals. Toxicity, pharmacokinetics, and molecular docking analyses were performed according to the established protocols.
Results: The hit compound, KBB-N2, a tetracyclic triterpene, was identified as an MM-targeted compound with cytotoxic effects. The primary mechanism of action of KBB-N2 in MM cells was inhibiting the activity of the mitochondrial electron transport (ETC) complex, resulting in the generation of excess intracellular reactive oxygen species (ROS), which led to tumor cell death by ROS-mediated apoptosis. In addition, exposure to KBB-N2 inhibited the activity of catalase, a powerful antioxidant enzyme in MM cells. Severe suppression of normal hematopoietic stem cell function was observed with lenalidomide administration at a concentration of 25 μM. However, this toxicity was not observed when KBB-N2 was administered at doses up to 60 μM. KBB-N2 activity involves PARP cleavage and caspase activation in the apoptotic pathway. Furthermore, KBB-N2 inhibited cell growth and exerted cytotoxicity. KBB-N2 induced apoptosis by activating the P53 apoptosis pathway in MM cells. In vivo, all untreated tumor-bearing mice showed rapid tumor growth and severe plasmacytomas, which led to death within seven weeks. Mice treated with KBB-N2 had significantly inhibited tumor growth and longer survival times. The molecular docking assay revealed the optimal docking conformation binding energy of KBB-N2 with docking scores (kcal/M) of -7.3 and -9.8 for ETC complexes I and III, respectively.
Conclusions: The triterpene compound, KBB-N2, was identified as a hit compound and may act as a targeted agent for MM treatment. The antimyeloma activity of KBB-N2 involves interference with the ETC complex and leads to MM cell death.
CD19/CD22 CAR T-Cell Therapy Following Autologous Transplantation Is an Optimizing Strategy in Relapsed/Refractory Central Nervous System Lymphoma
Authors: Yu Qiuxia , Gang Daizi , Wang Jue , Huang Liang , Li Chunrui , Zhang Yicheng , Zhou Xiaoxi , Cao Yang 
Published: December 2023

Background and Objectives: Relapsed/refractory (R/R) primary and secondary central nervous system lymphomas (PCNSL, SCNSL) are associated with short survival and represent an unmet need, requiring novel effective strategies.
Methods: We retrospectively compared the safety and efficacy of CD19/22 CAR T-cell therapy combined with HDT-ASCT (ASCT+CAR-T group), CD19/22 CAR T-cell cocktail therapy (CAR-T group) and targeted drugs combined with chemotherapy (Targeted drugs group) in treating R/R CNSL patients.
Results: The median age of the Targeted drugs group is older than that of the other two groups, 73.3%, 100% and 41.2% patients were secondary CNS lymphoma in ASCT+CAR-T group, CAR-T group and Targeted drugs group, respectively. The incidence of Grade 3/4 hematological toxicities in ASCT+CAR-T and CAR-T group was more than Targeted drugs group. Patients in two CAR-T therapy group exhibited comparable incidence and severity of CRS and ICANS. The ORR was 83.3% in ASCT+CAR-T group, 64.3% in CAR-T group and 58.8% in Targeted drugs group respectively (Figure 1). As of December 31, 2022, the median follow-up time after therapy was 15.53 months (range, 0.53-50.53 months). The median duration of OS and PFS was not reached in the ASCT+CAR-T group. The median PFS and OS in the CAR-T group were 3.07 months and 9.67 months, respectively. In the Targeted drugs group, the median PFS and OS were 6.63 months and 12.30 months, respectively. The 1-year PFS and OS rate of the patients in the ASCT+CAR-T group (66.67% and 76.52%) was significantly higher than that of the patients in the CAR-T group (18.75% and 50%) ( P=0.0006 and P=0.0253) and targeted drugs group (17.65% and 52.94%) ( P=0.0004 and P=0.0358) (Figure 1). In both univariable and multivariate analysis, PD before treatment was indicated worser PFS (HR: 3.134, 95% CI, 1.144 to 8.587, P=0.026), rather than OS, both in ASCT+CAR-T and CAR-T group and compared with CAR-T group, patients received ASCT+CAR-T treatment had better PFS (HR: 0.279, 95% CI, 0.120 to 0.651, P=0.003), rather than OS. PFS and OS of patients with PD before treatment, patients with ECOG ≥2, with high risk factors, and with＞3 prior lines of therapy in the ASCT+CAR-T group were superior to CAR-T group (Supplementary Figure 1). In the ASCT+CAR-T group, PFS, rather than OS, of patients without systemic disease in the ASCT+CAR-T group was superior to those with systemic disease ( P=0.0335).
Discussion: Our results support the development of CAR T -cells in R/R CNSL. With the durability of remission and low toxicity, ASCT combined with CART therapy appears to be a more effective and safe treatment option for primary and secondary relapsed/refractory CNS lymphoma.