bluuebunny/crossref_metadata_2025 huggingface dataset:
Acalabrutinib-based regimens in frontline or relapsed/refractory higher-risk CLL: pooled analysis of 5 clinical trials
Authors: Davids Matthew S. , Sharman Jeff P. , Ghia Paolo , Woyach Jennifer A. , Eyre Toby A. , Jurczak Wojciech , Siddiqi Tanya , Miranda Paulo , Shahkarami Mina , Butturini Anna , Emeribe Ugochinyere , Byrd John C.
Published: April 2024

Before targeted therapies, patients with higher-risk chronic lymphocytic leukemia (CLL), defined as del(17p) and/or TP53 mutation (TP53m), unmutated immunoglobulin heavy chain variable region genes (uIGHV), or complex karyotype (CK), had poorer prognosis with chemoimmunotherapy. Bruton tyrosine kinase inhibitors (BTKis) have demonstrated benefit in higher-risk patient populations with CLL in individual trials. To better understand the impact of the second-generation BTKi acalabrutinib, we pooled data from 5 prospective clinical studies of acalabrutinib as monotherapy or in combination with obinutuzumab (ACE-CL-001, ACE-CL-003, ELEVATE-TN, ELEVATE-RR, and ASCEND) in patients with higher-risk CLL in treatment-naive (TN) or relapsed/refractory (R/R) cohorts. A total of 808 patients were included (TN cohort, n = 320; R/R cohort, n = 488). Median follow-up was 59.1 months (TN cohort) and 44.3 months (R/R cohort); 51.3% and 26.8% of patients in the TN and R/R cohorts, respectively, remained on treatment at last follow-up. In the del(17p)/TP53m, uIGHV, and CK subgroups in the TN cohort, median progression-free survival (PFS) and median overall survival (OS) were not reached (NR). In the del(17p)/TP53m, uIGHV, and CK subgroups in the R/R cohort, median PFS was 38.6 months, 46.9 months, and 38.6 months, respectively, and median OS was 60.6 months, NR, and NR, respectively. The safety profile of acalabrutinib-based therapy in this population was consistent with the known safety profile of acalabrutinib in a broad CLL population. Our analysis demonstrates long-term benefit of acalabrutinib-based regimens in patients with higher-risk CLL, regardless of line of therapy.
Lysosomal degradation targets mutant calreticulin and the thrombopoietin receptor in myeloproliferative neoplasms
Authors: Kaur Amanpreet , Venkatesan Arunkumar , Kandarpa Malathi , Talpaz Moshe , Raghavan Malini
Published: April 2024

Somatic mutants of calreticulin (CRT) drive myeloproliferative neoplasms (MPNs) via binding to the thrombopoietin receptor (MPL) and aberrant activation of the JAK/STAT pathway. Compared with healthy donors, platelets from mutant CRT-expressing patients with MPN display low cell surface MPL. Additionally, coexpression of MPL with an MPN-linked CRT mutant (CRTDel52) reduces cell surface MPL, suggesting that CRTDel52 may induce MPL degradation. We show that lysosomal degradation is relevant to the turnover of CRTDel52 and MPL. Furthermore, CRTDel52 increases the lysosomal localization and degradation of MPL. Mammalian target of rapamycin (mTOR) inhibitors reduce cellular CRTDel52 and MPL, secreted CRTDel52 levels, and impair CRTDel52–mediated cell proliferation. mTOR inhibition also reduces colony formation and differentiation of CD34+ cells from patients with MPN but not from healthy donors. Together, these findings indicate that low-surface MPL is a biomarker of mutant CRT-mediated MPN and that induced degradation of CRTDel52 and MPL is an avenue for therapeutic intervention.
HLA reduction of human T cells facilitates generation of immunologically multicompatible cellular products
Authors: Winterhalter Pascal M. , Warmuth Linda , Hilgendorf Philipp , Schütz Julius M. , Dötsch Sarah , Tonn Torsten , Cicin-Sain Luka , Busch Dirk H. , Schober Kilian
Published: April 2024

Adoptive cellular therapies have shown enormous potential but are complicated by personalization. Because of HLA mismatch, rejection of transferred T cells frequently occurs, compromising the T-cell graft's functionality. This obstacle has led to the development of HLA knock-out (KO) T cells as universal donor cells. Whether such editing directly affects T-cell functionality remains poorly understood. In addition, HLA KO T cells are susceptible to missing self-recognition through natural killer (NK) cells and lack of canonical HLA class I expression may represent a safety hazard. Engineering of noncanonical HLA molecules could counteract NK-cell recognition, but further complicates the generation of cell products. Here, we show that HLA KO does not alter T-cell functionality in vitro and in vivo. Although HLA KO abrogates allogeneic T-cell responses, it elicits NK-cell recognition. To circumvent this problem, we demonstrate that selective editing of individual HLA class I molecules in primary human T cells is possible. Such HLA reduction not only inhibits T-cell alloreactivity and NK-cell recognition simultaneously, but also preserves the T-cell graft's canonical HLA class I expression. In the presence of allogeneic T cells and NK cells, T cells with remaining expression of a single, matched HLA class I allele show improved functionality in vivo in comparison with conventional allogeneic T cells. Since reduction to only a few, most frequent HLA haplotypes would already be compatible with large shares of patient populations, this approach significantly extends the toolbox to generate broadly applicable cellular products.
Recipient clonal hematopoiesis in allogeneic bone marrow transplantation for lymphoid malignancies
Authors: Imus Philip H. , Pasca Sergiu , Tsai Hua-Ling , Aljawai Yosra M. , Cooke Kenneth R. , Walston Jeremy D. , Gocke Christopher D. , Varadhan Ravi , Jones Richard J. , Gondek Lukasz P.
Published: April 2024

Allogeneic blood and marrow transplantation (alloBMT) is increasingly being used in older patients with blood cancer. Aging is associated with an increasing incidence of clonal hematopoiesis (CH). Although the effects of donor CH on alloBMT has been reported, the impact of recipient CH on alloBMT outcomes is unknown. In this retrospective study, alloBMT recipients age 60 and older with lymphoid malignancies were included. Among 97 consecutive patients who received alloBMT between 2017 and 2022, CH was detected in 60 (62%; 95% confidence interval [CI], 51-72). CH was found in 45% (95% CI, 28-64) of patients aged 60 to 64, 64% (95% CI, 44-81) of patients aged 65% to 69%, and 73% (95% CI, 59-87) in those above 70. Pretransplant CH was associated with worse survival after alloBMT: 3-year overall survival (OS) was 78% (95% CI, 65-94) for patients without CH vs 47% (95% CI, 35-63) for those with CH, (unadjusted HR, 3.1; [95% CI, 1.4-6.8; P < .001]). Nonrelapse mortality (NRM) was higher in patients with CH; cumulative incidence of NRM at 1-year was 11% (95% CI, 1-22) vs 35% (95% CI, 23-48), (HR, 3.4; [95% CI, 1.4-8.5], P = .009]). Among CH patients, worse OS and NRM was associated with CH burden and number of mutations. Recipient CH had no effect on relapse. In conclusion, older patients with CH experience worse outcomes after alloBMT, almost exclusively attributable to increased NRM. CH is a strong, independent predictor of outcomes. Novel strategies to ameliorate the adverse impacts of patient CH on transplant outcomes are being evaluated.
Final phase 1 substudy results of ivosidenib for patients with mutant IDH1 relapsed/refractory myelodysplastic syndrome
Authors: DiNardo Courtney D. , Roboz Gail J. , Watts Justin M. , Madanat Yazan F. , Prince Gabrielle T. , Baratam Praneeth , de Botton Stéphane , Stein Anthony , Foran James M. , Arellano Martha L. , Sallman David A. , Hossain Mohammad , Marchione Dylan M. , Bai Xiaofei , Patel Prapti A. , Kapsalis Stephanie M. , Garcia-Manero Guillermo , Fathi Amir T.
Published: April 2024

Ivosidenib is a first-in-class mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor with efficacy and tolerability in patients with advanced mIDH1 hematologic malignancies, leading to approval in frontline and relapsed/refractory (R/R) mIDH1 acute myeloid leukemia. We report final data from a phase 1 single-arm substudy of once-daily ivosidenib in patients with R/R mIDH1 myelodysplastic syndrome (MDS) after failure of standard-of-care therapies. Primary objectives were to determine safety, tolerability, and clinical activity. The primary efficacy end point was the complete remission (CR) + partial remission (PR) rate. Nineteen patients were enrolled; 18 were included in the efficacy analysis. Treatment-related adverse events occurred in 8 (42.1%) patients, including a grade 1 QT interval prolongation in 1 (5.3%) patient and grade 2 differentiation syndrome in 2 (10.5%) patients. Rates of CR + PR and objective response (CR + PR + marrow CR) were 38.9% (95% confidence interval [CI], 17.3-64.3) and 83.3% (95% CI, 58.6-96.4), respectively. Kaplan-Meier estimates showed a 68.6% probability of patients in CR achieving a remission duration of ≥5 years, and a median overall survival of 35.7 months. Of note, 71.4% and 75.0% baseline red blood cell (RBC)- and platelet-transfusion-dependent patients, respectively, became transfusion independent (TI; no transfusion for ≥56 days); 81.8% and 100% of baseline RBC and platelet TI patients, respectively, remained TI. One (5.3%) patient proceeded to a hematopoietic stem cell transplant. In conclusion, ivosidenib is clinically active, with durable remissions and a manageable safety profile observed in these patients. This trial was registered at www.ClinicalTrials.gov as #NCT02074839.
Rates of severe neutropenia and infection risk in patients treated with deferiprone: 28 years of data
Authors: Badawy Sherif M. , Palmblad Jan , Tricta Fernando , Toiber Temin Noemi , Fradette Caroline , Lin Leo , Rozova Anna , Sheth Sujit
Published: April 2024

Patients treated with deferiprone for transfusional iron overload may experience idiosyncratic drug–induced neutropenia (IDIN) that may increase risk of infection. This analysis examined the rates of severe IDIN and risk of serious infections at different absolute neutrophil count (ANC) levels during deferiprone treatment. Events of severe IDIN (ANC <0.5 × 109/L) and associated serious infections from clinical trials and postmarketing setting were analyzed by discrete ANC levels: group 1, 0.2 × 109/L to 0.5 × 109/L; group 2, 0.1 × 109/L to 0.199 × 109/L; group 3, <0.1 × 109/L. In clinical trials, 22 events of severe IDIN occurred (group 1, n = 9; group 2, n = 3; group 3, n = 10), and rates of severe IDIN per 100 patient-years were 0.45 in group 1; 0.15 in group 2; and 0.50 in group 3 (1990.26 patient-years deferiprone exposure). All serious infections were in group 3 (3/10 [30.0%]). In the postmarketing setting, 176 events of severe IDIN were reported (group 1, n = 65; group 2, n = 20; group 3, n = 91) and rates of severe IDIN per 100 patient-years were 0.06 in group 1; 0.02 in group 2; and 0.08 in group 3 (111 570.24 patient-years deferiprone exposure). Rates of serious infection were 7.7% (5/65) in group 1; 10% (2/20) in group 2; and 13.2% (12/91) in group 3. Our findings suggest a high risk of serious infections with ANC <0.2 × 109/L during deferiprone treatment, a level consistent with the recent neutropenia guidelines.
Multicenter, phase 1 study of etavopivat (FT-4202) treatment for up to 12 weeks in patients with sickle cell disease
Authors: Saraf Santosh L. , Hagar Robert , Idowu Modupe , Osunkwo Ifeyinwa , Cruz Kimberly , Kuypers Frans A. , Brown R. Clark , Geib James , Ribadeneira Maria , Schroeder Patricia , Wu Eric , Forsyth Sanjeev , Kelly Patrick F. , Kalfa Theodosia A. , Telen Marilyn J.
Published: April 2024

Etavopivat is an investigational, once daily, oral, selective erythrocyte pyruvate kinase (PKR) activator. A multicenter, randomized, placebo-controlled, double-blind, 3-part, phase 1 study was conducted to characterize the safety and clinical activity of etavopivat. Thirty-six patients with sickle cell disease (SCD) were enrolled into 4 cohorts: 1 single-dose, 2 multiple ascending doses, and 1 open-label (OL). In the OL cohort, 15 patients (median age 33.0 years [range, 17-55]) received 400 mg etavopivat once daily for 12 weeks; 14 patients completed treatment. Consistent with the mechanism of PKR activation, increases in adenosine triphosphate and decreases in 2,3-diphosphoglycerate were observed and sustained over 12 weeks’ treatment. This translated clinically to an increase in hemoglobin (Hb; mean maximal increase 1.6 g/dL [range, 0.8-2.8]), with >1 g/dL increase in 11 (73%) patients during treatment. In addition, the oxygen tension at which Hb is 50% saturated was reduced (P = .0007) with a concomitant shift in point of sickling (P = .0034) to lower oxygen tension in oxygen-gradient ektacytometry. Hemolysis markers (absolute reticulocyte count, indirect bilirubin, and lactate dehydrogenase) decreased from baseline, along with matrix metalloproteinase-9 and erythropoietin. In the OL cohort, adverse events (AEs) were mostly grade 1/2, consistent with underlying SCD; 5 patients had serious AEs. Vaso-occlusive pain episode was the most common treatment-emergent AE (n = 7) in the OL cohort. In this, to our knowledge, the first study of etavopivat in SCD, 400 mg once daily for 12 weeks was well tolerated, resulting in rapid and sustained increases in Hb, improved red blood cell physiology, and decreased hemolysis. This trial was registered at www.ClinicalTrials.gov as #NCT03815695.
A 69 long noncoding RNA signature predicts relapse and acts as independent prognostic factor in pediatric AML
Authors: Ren Zhiyao , Vanhooren Jolien , Derpoorter Charlotte , De Moerloose Barbara , Lammens Tim
Published: April 2024

Risk stratification using genetics and minimal residual disease has allowed for an increase in the cure rates of pediatric acute myeloid leukemia (pedAML) to up to 70% in contemporary protocols. Nevertheless, ∼30% of patients still experience relapse, indicating a need to optimize stratification strategies. Recently, long noncoding RNA (lncRNA) expression has been shown to hold prognostic power in multiple cancer types. Here, we aimed at refining relapse prediction in pedAML using lncRNA expression. We built a relapse–related lncRNA prognostic signature, named AMLlnc69, using 871 transcriptomes of patients with pedAML obtained from the Therapeutically Applicable Research to Generate Effective Treatments repository. We identified a 69 lncRNA signature AMLlnc69 that is highly predictive of relapse risk (c-index = 0.73), with area under the receiver operating characteristic curve (AUC) values for predicting the 1-, 2-, and 3-year relapse-free survival (RFS) of 0.78, 0.77, and 0.77, respectively. The internal validation using a bootstrap method (resampling times = 1000) resulted in a c-index of 0.72 and AUC values for predicting the 1-, 2-, and 3-year RFS of 0.77, 0.76, and 0.76, respectively. Through a Cox regression analysis, AMLlnc69, nucleophosmin mutation, and white blood cell at diagnosis were identified as independent predictors of RFS. Finally, a nomogram was build using these 2 parameters, showing a c-index of 0.80 and 0.71 after bootstrapping (n = 1000). In conclusion, the identified AMLlnc69 will, after prospective validation, add important information to guide the management of patients with pedAML. The nomogram is a promising tool for easy stratification of patients into a novel scheme of relapse-risk groups.
Diagnostic value of the pepsin concentration in saliva and induced sputum for gastroesophageal reflux-induced chronic cough: a prospective clinical study
Authors: Gu Wenhua , Chen Wei , Zhang Tongyangzi , Zhu Yiqing , Li Wanzhen , Shi Wenbo , Li Na , Wang Shengyuan , Xu Xianghuai , Yu Li
Published: April 2024

Background

Finding a simple, effective and rapid diagnostic method to improve the diagnosis of gastroesophageal reflux-induced chronic cough (GERC) is indicated. Our objective was to determine the diagnostic value of the pepsin concentration in saliva and induced sputum for GERC.

Methods

171 patients with chronic cough were enrolled. The diagnosis and treatment followed the chronic cough diagnosis and treatment protocol. Saliva and induced sputum were collected, and the pepsin concentration was determined using Peptest. A Gastroesophageal Reflux Diagnostic Questionnaire (GerdQ) was completed. The diagnostic value of the pepsin concentration in saliva and induced sputum for GERC was analysed and compared.

Results

The salivary pepsin concentration predicted GERC with an area under the receiver operating characteristic curve (AUC) of 0.845. The optimal cut-off value was 76.10 ng·mL−1, the sensitivity was 83.58% and the specificity was 82.69%. The pepsin concentration in the induced sputum supernatant for GERC had an AUC of 0.523. When GerdQ was used for GERC diagnosis, the AUC was 0.670 and the diagnostic value of salivary pepsin was better compared to GerdQ (DeLong test, p=0.0008). Salivary pepsin had a comparable diagnostic value to GerdQ (AUC 0.779versus0.826; p=0.4199) in acidic GERC. Salivary pepsin had superior diagnostic value compared to GerdQ (AUC 0.830versus0.533; p<0.0001) in non-acidic GERC.

Conclusions

A salivary pepsin concentration >76.10 ng·mL−1is of good diagnostic value for GERC, especially in non-acidic GERC. The pepsin concentration in induced sputum has a low diagnostic value.
Epidemiology of patients with severe asthma in Japan: a nationwide descriptive study
Authors: Kimura Yuya , Suzukawa Maho , Jo Taisuke , Hashimoto Yohei , Kumazawa Ryosuke , Ishimaru Miho , Matsui Hiroki , Yokoyama Akira , Tanaka Goh , Yasunaga Hideo
Published: April 2024

Background

The 2014 European Respiratory Society/American Thoracic Society guidelines defined severe asthma based on treatment intensity and estimated the proportion of severe asthma among all asthma cases to be 5–10%. However, data supporting the estimate and comprehensive and sequential data on asthma cases are scarce. We aimed to estimate the national prevalence and proportion of severe asthma during the last decade.

Methods

Using a Japanese national administrative database, which covers ≥99% of the population, we evaluated the prevalence and proportion of severe asthma in 2013, 2015, 2017 and 2019. Additionally, we elucidated the demographic characteristics, treatments and outcomes of patients with asthma.

Results

The national prevalence of mild–moderate and severe asthma in 2019 was 800 and 36 per 100 000 persons, respectively. While the prevalence of mild–moderate asthma remained almost constant in the study years, the prevalence of severe asthma decreased, resulting in a reduction in the proportion of severe asthma from 5.6% to 4.3%. Although treatment modalities have evolved, such as the increased use of combination inhalers and asthma biologics, approximately 15% of mild–moderate and 45% of severe asthma cases were still considered “uncontrolled”. The number of deaths from asthma decreased in patients with both mild–moderate and severe asthma.

Conclusions

This study revealed that the prevalence of severe asthma in Japan decreased during the study period and fell below 5% in the most recent data. Despite treatment evolution, a substantial proportion of patients with both mild–moderate and severe asthma still have poor asthma control.
Longitudinal change in ultrasound-derived rectus femoris cross-sectional area in COPD
Authors: Jenkins Timothy O. , Patel Suhani , Edwards George D. , Nolan Claire M. , Canavan Jane , Kon Samantha , Jones Sarah , Barker Ruth E. , Littlemore Hannah , Maddocks Matthew , Man William D-C.
Published: April 2024

Background

Skeletal muscle dysfunction is common in COPD. Ultrasound-derived rectus femoris cross-sectional area (RFCSA) is a radiation free, non-invasive measure of muscle bulk that relates to quadriceps strength in people with COPD. However, there are limited longitudinal data for RFCSA, and it is not known whether longitudinal change in RFCSA reflects change in quadricep strength, exercise capacity, lower limb function or muscle mass. We aimed to quantify longitudinal change in ultrasound-derived RFCSA and assess its relationship with change in quadriceps maximal voluntary contraction (QMVC), incremental shuttle walk test (ISWT), five-repetition sit-to-stand (5STS) and fat-free mass (FFM) over 12 months in people with COPD.

Methods

We measured ultrasound-derived RFCSA, QMVC, ISWT, 5STS and FFM (measured by bioelectric impedance analysis) at baseline and 12 months in 169 people with stable COPD. Change was correlated using Pearson's or Spearman's coefficients.

Results

Baseline characteristics: mean±sdage 70.4±9.4 years; FEV153.3±18.9% predicted. Over the course of 12 months mean RFCSA change was −33.7 mm2(99% CI −62.6– −4.9 mm2; p=0.003) representing a mean±sdpercentage change of −1.8±33.5%. There was a weak correlation between change in RFCSA and FFM (r=0.205, p=0.009), but not with change in QMVC, ISWT or 5STS.

Conclusion

There is a statistically significant decrease in ultrasound-derived RFCSA over 12 months in people with stable COPD, but this decrease does not correlate with change in quadriceps strength, exercise capacity, FFM or lower limb function.
Prognostic role of haemodynamics at follow-up in patients with pulmonary arterial hypertension: a challenge to current European Society of Cardiology/European Respiratory Society risk tools
Authors: Dardi Fabio , Guarino Daniele , Ballerini Alberto , Bertozzi Riccardo , Donato Federico , Cennerazzo Francesco , Salvi Monica , Nardi Elena , Magnani Ilenia , Manes Alessandra , Galiè Nazzareno , Palazzini Massimiliano
Published: April 2024

Background

Haemodynamic variables like right atrial pressure (RAP), cardiac index (CI), stroke volume index (SVI) and mixed venous oxygen saturation (SvO2) predict survival in patients with pulmonary arterial hypertension (PAH). However, there is the need to identify further prognostic haemodynamic parameters as well as to redefine their role in PAH risk stratification compared to current risk tools and non-invasive parameters.

Methods

This cohort study includes treatment-naïve patients assessed at baseline and after first-line PAH therapy with clinical, functional, exercise, laboratory and haemodynamic evaluations. Using a stepwise multivariate Cox regression analysis, independent prognostic haemodynamic parameters were identified and stratified according to cut-offs already defined in the European Society of Cardiology (ESC)/European Respiratory Society (ERS) risk table or defined based on the highest Chi-squared of the log-rank test. Their discriminatory power was tested for all-cause death and a combined end-point of death, hospitalisation and need of treatment escalation.

Results

794 patients with PAH were enrolled. At first follow-up, RAP and pulmonary artery elastance were independently associated with death. Because of high correlations between haemodynamic parameters, different multivariable analyses were done identifying six other variables (pulmonary arterial compliance, cardiac efficiency, pulmonary vascular resistance,SvO2, CI and SVI). Haemodynamic parameters were of no added prognostic value compared to ESC/ERS risk tools for the all-cause death end-point but they showed additional value to non-invasive parameters for the combined end-point and, when taken alone, had a discriminatory capacity comparable to ESC/ERS risk tools.

Conclusion

Haemodynamics’ discriminative ability for clinical worsening is comparable to current ESC/ERS risk tools and is of added value to non-invasive parameters.
Patients at risk of nontuberculous mycobacterial pulmonary disease who need testing evaluated using a modified Delphi process by European experts
Authors: Loebinger Michael R. , Aliberti Stefano , Haworth Charles , Jankovic Makek Mateja , Lange Christoph , Lorent Natalie , Papavasileiou Apostolos , Polverino Eva , Rohde Gernot , Veziris Nicolas , Wagner Dirk , van Ingen Jakko
Published: April 2024

Background

Identifying patients at risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) is challenging. Delays in NTM-PD identification and management are associated with declining lung function and increased morbidity and mortality.

Study design and methods

European NTM-PD experts (n=12) participated in a three-round modified Delphi process to score symptoms and comorbidities potentially associated with NTM-PD as reasons to test for nontuberculous mycobacteria.

Results

Experts reached a consensus on the symptoms and comorbidities that should and should not prompt testing for nontuberculous mycobacteria. Requirements for testing were scored as high (mean ≥7), medium (mean ≥4–<7) or low (mean <4). Nontuberculous mycobacteria testing should be undertaken when multiple suggestive symptoms are present simultaneously in all patients except those with cancer (7.3–8.8), or when radiology is indicative of NTM-PD (≥8.9). Symptoms of persistent sputum production, recurrent respiratory infection and haemoptysis should prompt testing for nontuberculous mycobacteria, particularly in those with underlying respiratory diseases. Symptomatic patients with bronchiectasis or previous tuberculosis/NTM-PD or those being prescribed or undergoing long-term macrolide therapy for a respiratory condition should also be tested. Testing is not warranted in patients without an underlying respiratory disorder or in those without a history of respiratory disorders unless presenting with multiple symptoms.

Conclusions

Assessing patients’ risk of NTM-PD is challenging. This Delphi consensus process provides insight into symptoms and clinical characteristics that should prompt NTM-PD assessment. Timely testing and diagnosis would enable initiation of appropriate management.
A robust web-based tool to predict viral shedding in patients with Omicron SARS-CoV-2 variants
Authors: Zhang Weilong , Gai Xiaoyan , Wang Ben , Duan Zhonghui , Zhou Qingtao , Dai Lili , Yan Changjian , Wu Chaoling , Fan Jiarun , Wang Ping , Yang Ping , Bao Fang , Jing Hongmei , Cai Chao , Song Chunli , Ma Yingmin , Sun Yongchang
Published: April 2024

Background

Data on viral kinetics and variants affecting the duration of viral shedding were limited. Our objective was to determine viral shedding in distinct severe acute respiratory syndrome coronavirus 2 variants, including Omicron BA.4/5 and BF.7, and to identify the relevant influencing factors.

Methods

We carried out a longitudinal cohort study at Beijing Xiaotangshan Fangcang shelter hospital from May to June 2022 (Omicron BA.4/5) and from November to December 2022 (Omicron BF.7). Nucleocapsid protein (N) and open reading frame (ORF) genes were considered as the target genes of the reverse transcription PCR. The daily results of cycle threshold (CT), including lowest ORF1ab-CT values for days 1–3 post-hospitalisation and lowest N-CT values for days 1–3 post-hospitalisation (CT3minN) and demographic and clinical characteristics were collected.

Results

1433 patients with coronavirus disease 2019 (COVID-19) were recruited from the Fangcang shelter hospital, in which 278 patients were diagnosed with Omicron BA.4/5 and 1155 patients with Omicron BF.7. Patients with BF.7 infection showed a longer duration of viral shedding. The duration of viral shedding was associated with the variants age, alcohol use, the severity of COVID-19 and CT3minN. Moreover, the nomogram had excellent accuracy in predicting viral shedding.

Conclusions

Our results indicated that patients with Omicron BF.7 had a longer period of contagiousness than those with BA.4/5. The duration of viral shedding was affected by a variety of factors and the nomogram may become an applicable clinical instrument to predict viral shedding. Furthermore, we developed a new COVID-19 viral shedding predicting model that can accurately predict the duration of viral shedding for COVID-19, and created a user-friendly website to apply this prediction model (https://puh3.shinyapps.io/CVSP_Model/).
Interpretable machine learning-based clinical prediction model for predicting lymph node metastasis in patients with intrahepatic cholangiocarcinoma
Authors: Xie Hui , Hong Tao , Liu Wencai , Jia Xiaodong , Wang Le , Zhang Huan , Xu Chan , Zhang Xiaoke , Li Wen-Le , Wang Quan , Yin Chengliang , Lv Xu
Published: April 2024

Objective

Prediction of lymph node metastasis (LNM) for intrahepatic cholangiocarcinoma (ICC) is critical for the treatment regimen and prognosis. We aim to develop and validate machine learning (ML)-based predictive models for LNM in patients with ICC.

Methods

A total of 345 patients with clinicopathological characteristics confirmed ICC from Jan 2007 to Jan 2019 were enrolled. The predictors of LNM were identified by the least absolute shrinkage and selection operator (LASSO) and logistic analysis. The selected variables were used for developing prediction models for LNM by six ML algorithms, including Logistic regression (LR), Gradient boosting machine (GBM), Extreme gradient boosting (XGB), Random Forest (RF), Decision tree (DT), Multilayer perceptron (MLP). We applied 10-fold cross validation as internal validation and calculated the average of the areas under the receiver operating characteristic (ROC) curve to measure the performance of all models. A feature selection approach was applied to identify importance of predictors in each model. The heat map was used to investigate the correlation of features. Finally, we established a web calculator using the best-performing model.

Results

In multivariate logistic regression analysis, factors including alcoholic liver disease (ALD), smoking, boundary, diameter, and white blood cell (WBC) were identified as independent predictors for LNM in patients with ICC. In internal validation, the average values of AUC of six models ranged from 0.820 to 0.908. The XGB model was identified as the best model, the average AUC was 0.908. Finally, we established a web calculator by XGB model, which was useful for clinicians to calculate the likelihood of LNM.

Conclusion

The proposed ML-based predicted models had a good performance to predict LNM of patients with ICC. XGB performed best. A web calculator based on the ML algorithm showed promise in assisting clinicians to predict LNM and developed individualized medical plans.
Development and validation of a novel nomogram model for predicting delayed graft function in deceased donor kidney transplantation based on pre-transplant biopsies
Authors: Li Meihe , Hu Xiaojun , Li Yang , Chen Guozhen , Ding Chen-guang , Tian Xiaohui , Tian Puxun , Xiang Heli , Pan Xiaoming , Ding Xiaoming , Xue Wujun , Zheng Jin
Published: April 2024

Background

Delayed graft function (DGF) is an important complication after kidney transplantation surgery. The present study aimed to develop and validate a nomogram for preoperative prediction of DGF on the basis of clinical and histological risk factors.

Methods

The prediction model was constructed in a development cohort comprising 492 kidney transplant recipients from May 2018 to December 2019. Data regarding donor and recipient characteristics, pre-transplantation biopsy results, and machine perfusion parameters were collected, and univariate analysis was performed. The least absolute shrinkage and selection operator regression model was used for variable selection. The prediction model was developed by multivariate logistic regression analysis and presented as a nomogram. An external validation cohort comprising 105 transplantation cases from January 2020 to April 2020 was included in the analysis.

Results

266 donors were included in the development cohort, 458 kidneys (93.1%) were preserved by hypothermic machine perfusion (HMP), 96 (19.51%) of 492 recipients developed DGF. Twenty-eight variables measured before transplantation surgery were included in the LASSO regression model. The nomogram consisted of 12 variables from donor characteristics, pre-transplantation biopsy results and machine perfusion parameters. Internal and external validation showed good discrimination and calibration of the nomogram, with Area Under Curve (AUC) 0.83 (95%CI, 0.78–0.88) and 0.87 (95%CI, 0.80–0.94). Decision curve analysis demonstrated that the nomogram was clinically useful.

Conclusion

A DGF predicting nomogram was developed that incorporated donor characteristics, pre-transplantation biopsy results, and machine perfusion parameters. This nomogram can be conveniently used for preoperative individualized prediction of DGF in kidney transplant recipients.
Continued versus discontinued oxytocin stimulation in the active phase of labour (CONDISOX): individual management based on artificial intelligence - a secondary analysis
Authors: Boie Sidsel , Glavind Julie , Bor Pinar , Steer Philip , Riis Anders Hammerich , Thiesson Bo , Uldbjerg Niels
Published: April 2024

Background

Current guidelines regarding oxytocin stimulation are not tailored to individuals as they are based on randomised controlled trials. The objective of the study was to develop an artificial intelligence (AI) model for individual prediction of the risk of caesarean delivery (CD) in women with a cervical dilatation of 6 cm after oxytocin stimulation for induced labour. The model included not only variables known when labour induction was initiated but also variables describing the course of the labour induction.

Methods

Secondary analysis of data from the CONDISOX randomised controlled trial of discontinued vs. continued oxytocin infusion in the active phase of induced labour. Extreme gradient boosting (XGBoost) software was used to build the prediction model. To explain the impact of the predictors, we calculated Shapley additive explanation (SHAP) values and present a summary SHAP plot. A force plot was used to explain specifics about an individual’s predictors that result in a change of the individual’s risk output value from the population-based risk.

Results

Among 1060 included women, 160 (15.1%) were delivered by CD. The XGBoost model found women who delivered vaginally were more likely to be parous, taller, to have a lower estimated birth weight, and to be stimulated with a lower amount of oxytocin. In 108 women (10% of 1060) the model favoured either continuation or discontinuation of oxytocin. For the remaining 90% of the women, the model found that continuation or discontinuation of oxytocin stimulation affected the risk difference of CD by less than 5% points.

Conclusion

In women undergoing labour induction, this AI model based on a secondary analysis of data from the CONDISOX trial may help predict the risk of CD and assist the mother and clinician in individual tailored management of oxytocin stimulation after reaching 6 cm of cervical dilation.
Association between sleep quality with maternal and neonatal outcomes during the covid-19 pandemic
Authors: Akbari Maryam , EsmaeilzadehSaeieh Sara , Farid Malihe , Shafiee Arman , Bakhtiyari Mahmood , Bahrami Babaheidari Touran , Yazdkhasti Mansoureh
Published: April 2024

Aim

Sleep disorders during pregnancy can impact maternal and neonatal outcomes. The objective of this study is to examine the relationship between sleep quality and maternal and neonatal outcomes during the COVID-19 pandemic.

Method

This prospective cohort study was conducted at the Educational-Therapeutic Center of Shohadaye Yaftabad Referral Hospital in Tehran, Iran, from December 2020 to September 2022. A total of 198 eligible participants were randomly assigned to either the sleep disorders group or the no sleep disorders group. Data were collected through demographic questionnaires, the Corona Disease Anxiety Scale (CDAS) questionnaire, the Pittsburgh Sleep Quality Index (PSQI), and the checklist for maternal and neonatal outcomes.

Results

At baseline, the sleep disorders and no sleep disorders groups were similar in terms of age, body mass index (before pregnancy), education level, employment status, gravida, parity, abortion, and history of COVID-19. Within the sleep disorders group, there was a statistically significant, direct linear correlation between sleep disorders and FBS 34–36 weeks (r = 0.33, P < 0.001) as well as Corona Disease Anxiety (CDA) (r = 0.35, P < 0.001). The linear regression results indicated that for every unit increase in sleep disorders, the risk of FBS 34–36 weeks increased by 1.09 times (β = 1.09, P < 0.001). Additionally, sleep disorders increased the risk of CDA by 1.36 times (β = 1.36, P < 0.001). The results showed no statistically significant differences in terms of birth weight, type of delivery (vaginal or cesarean section), gestational age (preterm or full term), length of labor stages (first and second stage), Apgar score at minutes 1 and 5, and NICU admission between the two groups.

Conclusion

Based on the results, a certain degree of correlation exists between sleep quality and FBS at 34–36 weeks and CDA. These findings underscore the need for future public health guidelines to formulate detailed strategies to improve sleep quality during the COVID-19 pandemic.
Real-world evidence from a retrospective study on suicide during depression: clinical characteristics, treatment patterns and disease burden
Authors: Wang Han , Lyu Nan , Huang Juan , Fu Bingbing , Shang Lili , Yang Fan , Zhao Qian , Wang Gang
Published: April 2024

Background

Suicide stands as both a primary symptom and the direst outcome of major depressive disorder (MDD). The scarcity of effective treatment strategies makes managing MDD patients with suicide especially challenging. Hence, it is crucial to investigate disease characteristics and efficacious therapeutic strategies for these patients, drawing insights from disease databases and real-world data.

Methods

In this retrospective study, MDD patients hospitalized between January 2013 and December 2020 were investigated using Electronic Health Records (EHR) data from Beijing Anding Hospital. The study enrolled 4138 MDD patients with suicidal ideation or behavior (MDS) and 3848 without (MDNS). Demographic data, clinical attributes, treatment approaches, disease burden, and re-hospitalization within one year of discharge were extracted and compared.

Results

Patients in the MDS group were predominantly younger and female, exhibiting a higher prevalence of alcohol consumption, experiencing frequent life stress events, and having an earlier onset age. Re-hospitalizations within six months post-discharge in the MDS group were significantly higher than in the MDNS group (11.36% vs. 8.91%, p < 0.001). Moreover, a more considerable fraction of MDS patients underwent combined electroconvulsive therapy treatment (56.72% vs. 43.71%, p < 0.001). Approximately 38% of patients in both groups were prescribed two or more therapeutic regimes, and over 90% used antidepressants, either alone or combined. Selective serotonin reuptake inhibitors (SSRIs) were the predominant choice in both groups. Furthermore, antidepressants were often prescribed with antipsychotics or mood stabilizers. When medication alterations were necessary, the favoured options involved combination with antipsychotics or transitioning to alternative antidepressants. Yet, in the MDS group, following these initial modifications, the addition of mood stabilizers tended to be the more prioritized alternative.

Conclusions

MDD patients with suicidal ideation or behaviour displayed distinctive demographic and clinical features. They exhibited intricate treatment patterns, a pronounced burden of illness, and an increased likelihood of relapse.
Cervical cancer screening among women with comorbidities: evidence from the 2022 Tanzania demographic and health survey
Authors: Okyere Joshua , Ayebeng Castro , Dosoo Abigail Kabukie , Dickson Kwamena Sekyi
Published: April 2024

Background

The aim of this study is to examine cervical cancer screening (CCS) uptake among women living with hypertension and HIV in Tanzania.

Methods

We used the recently released 2022 Tanzania Demographic and Health Survey. The outcome variable assessed in the study was CCS, whereas chronic morbidities constituted the main explanatory variable. Data analysis was based on observations from 6,298 women aged 30–49 years. Multivariable logistic regression models were used to determine the association between hypertension and HIV status, and CCS uptake. The analyses were computed in STATA 18.

Results

Out of the 6,298 respondents, only 805 (12.8%) had undergone CCS with higher screening uptake among those living with either one of the disease (28.5%) than among those living with neither hypertension or HIV. The highest proportion was found among those who had ever been diagnosed with hypertension (24.1%) and among women with positive HIV test results (36.7%). There was a significantly higher likelihood of undergoing screening for cervical cancer among women living with at least one of the diseases [AOR = 2.4; 95% CI: 1.4–2.8], compared to those without these conditions. Women diagnosed with hypertension showed increased likelihood of undergoing CCS [AOR = 1.4; 95%CI: 1.1–1.7]. Similarly, women with a positive HIV test result demonstrated higher odds of screening uptake [AOR = 5.2; 95%CI: 4.0-6.7].

Conclusion

The study found a positive association between comorbidities and CCS uptake in Tanzanian women. Our findings emphasize the critical importance of ensuring accessibility and adherence to essential screenings for individuals with chronic morbid conditions. Future efforts should focus on strengthening existing integrated services and identifying potential barriers to accessing CCS within these healthcare settings to optimize cervical cancer prevention efforts for individuals with chronic morbidities.
Effect of acidic environment on color and translucency of different indirect restorative materials
Authors: Omara Abdelaziz A. , Othman Hesham I. , Aldamaty Mohamed F. , Metwally Mohamed F.
Published: April 2024

Purpose

The aim of the current study was to evaluate the effect of simulated gastric acid on the color and translucency of different indirect restorative materials.

Materials and methods

A total of 36 disc-shaped samples were cut by using an isomet saw and divided into four equal groups (n = 9) according to the material type: Group Z: translucent zirconia (Ceramill® Zolid ht.+ preshade, Amann Girrbach, Koblach, Austria); Group E: lithium disilicate (IPS e.max CAD, Ivoclar Vivadent AG, Schaan, Liechtenstein); Group C: resin nanoceramic (Cerasmart, GC, Tokyo, Japan); Group P: polyether ether ketone (PEEK) (Bettin Zirconia Dentale Italy) veneered with indirect high impact polymer composite (HIPC) (breCAM HIPC, Bredent GmbH & Co. KG, Germany). The samples were immersed in simulated gastric acid (HCl, pH 1.2) for 96 hours at 37 °C in an incubator. The color change (ΔE00) and translucency (RTP00) were measured every 9.6 hours (one-year clinical simulation) of immersion in simulated gastric acid.

Results

For color change (∆E00) and translucency (RTP00) among the tested materials, there was a highly statistically significant difference (P < 0.001) after every year of follow-up. The color change in both Z and G groups was the lowest after 1 year of acid immersion, followed by that in group H, and the highest change in color was recorded in group P.

Conclusion

High translucent zirconia is recommended in patients who are concerned about esthetic, especially with acidic oral environment.
Evidence on the inhibitory effect of Brassica plants against Acinetobacter baumannii lipases: phytochemical analysis, in vitro, and molecular docking studies
Authors: Sabry Manal M. , El-Halawany Ali M. , Fahmy Walaa G. , Eltanany Basma M. , Pont Laura , Benavente Fernando , Attia Ahmed S. , Sherbiny Farag F. , Ibrahim Rana M.
Published: April 2024

Background

Infections caused by Acinetobacter baumannii are becoming a rising public health problem due to its high degree of acquired and intrinsic resistance mechanisms. Bacterial lipases penetrate and damage host tissues, resulting in multiple infections. Because there are very few effective inhibitors of bacterial lipases, new alternatives for treating A. baumannii infections are urgently needed. In recent years, Brassica vegetables have received a lot of attention since their phytochemical compounds have been directly linked to diverse antimicrobial actions by inhibiting the growth of various Gram-positive and Gram-negative bacteria, yeast, and fungi. Despite their longstanding antibacterial history, there is currently a lack of scientific evidence to support their role in the management of infections caused by the nosocomial bacterium, A. baumannii. This study aimed to address this gap in knowledge by examining the antibacterial and lipase inhibitory effects of six commonly consumed Brassica greens, Chinese cabbage (CC), curly and Tuscan kale (CK and TK), red and green Pak choi (RP and GP), and Brussels sprouts (BR), against A. baumannii in relation to their chemical profiles.

Methods

The secondary metabolites of the six extracts were identified using LC-QTOF-MS/MS analysis, and they were subsequently correlated with the lipase inhibitory activity using multivariate data analysis and molecular docking.

Results

In total, 99 metabolites from various chemical classes were identified in the extracts. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) revealed the chemical similarities and variabilities among the specimens, with glucosinolates and phenolic compounds being the major metabolites. RP and GP showed the highest antibacterial activity against A. baumannii, followed by CK. Additionally, four species showed a significant effect on the bacterial growth curves and demonstrated relevant inhibition of A. baumannii lipolytic activity. CK showed the greatest inhibition (26%), followed by RP (21%), GP (21%), and TK (15%). Orthogonal partial least squares-discriminant analysis (OPLS-DA) pinpointed 9 metabolites positively correlated with the observed bioactivities. Further, the biomarkers displayed good binding affinities towards lipase active sites ranging from −70.61 to −30.91 kcal/mol, compared to orlistat.

Conclusion

This study emphasizes the significance of Brassica vegetables as a novel natural source of potential inhibitors of lipase from A. baumannii.
Impact of virtual problem-based learning of cardiopulmonary resuscitation on fourth-year nursing students’ satisfaction and performance: a quasi-experimental study
Authors: Falahan Seyedeh Nayereh , Habibi Edris , Kamyari Naser , Yousofvand Vahid
Published: April 2024

Background

Regarding competency of nursing students in cardiopulmonary resuscitation (CPR), nursing students frequently exhibit inadequate performance and low satisfaction levels regarding CPR training methods. The problem-based learning (PBL) method, characterized by a constructivist approach, has been underutilized for CPR training, particularly in a virtual format. Hence, this study aims to assess the influence of virtual problem-based learning in cardiopulmonary resuscitation on the satisfaction and performance of fourth-year nursing students.

Methods

This quasi-experimental study, conducted in 2022, involved 80 final-year nursing students from Hamadan University of Medical Sciences, Iran. The participants were randomly assigned to either the experimental group (N = 40) or the control group (N = 40). The experimental group was further divided into six smaller groups on WhatsApp. Both groups initially received routine training sessions, after which the experimental group engaged in four problem-based learning sessions across three different scenarios. Data collection included demographic information, a teaching satisfaction questionnaire, and cardiopulmonary resuscitation checklists administered immediately and one month after the intervention.

Results

The study was initiated and concluded with 80 participants. The study commenced with no significant disparity in the mean scores of cardiopulmonary resuscitation performance, encompassing chest compressions (P = 0.451) and airway management (P = 0.378), as well as teaching satisfaction (p = 0.115) among the nursing students between the experimental and control groups. However, subsequent to the intervention, both immediately and one month later, the experimental group displayed notable enhancements in mean scores for cardiopulmonary resuscitation performance, comprising chest compressions (p < 0.001) and airway management (p < 0.001), as well as teaching satisfaction (p < 0.001) compared to the control group.

Conclusion

Based on the study’s findings, it is recommended that nursing educators implement this approach in their teaching practices.