bluuebunny/crossref_metadata_2025_split huggingface dataset:
A role for pelvic sentinel lymph nodes in lower extremity melanoma?
Authors: Laakkonen Juulia , Kaarela Outi , Tervala Tomi , Nuutinen Henrik 
Published: January 2023

Background and objective: Consensus on management of pelvic sentinel lymph nodes (PSLNs) has not been reached and thus the extent of sentinel lymph node biopsy (SLNB) of the groin in melanoma patients varies among centers and surgeons. Lymphatic drainage to PSLNs is often identified in, but the diagnostic and clinical relevance of PSLNs has been debated. Our aim was to determine if the presence of PSLNs affected recurrence or survival rates in patients with melanoma in the lower extremities. Methods: This retrospective study consisted of 702 patients with cutaneous melanoma operated between 2005 and 2018. Of these, 134 patients with melanoma in the lower extremities were included in the study. Images of lymphoscintigraphy and SPECT-CT studies were thoroughly observed together with surgery reports to define the status of SLNs. Results: Overall, 85 of 134 patients went through SLNB and 28 of them had PSLN identified. Two had their PSLN removed, which led 26 patients with PSLN to be compared to the 57 who did not have PSLN identified. We did not find statistically significant differences in overall recurrence (26.9% versus 28.0%, p = 1.00), regional nodal recurrence (11.5% versus 15.8%, p = 0.67), local or in-transit recurrence (19.2% versus 8.8%, p = 0.17), or distant recurrence rates (15.4% versus 19.3%, p = 0.66). Disease-free survival did not differ between the groups (median 23.0 (IQR 15.0–39.0) versus 19.0 (IQR 10.3–61.8) months, p = 0.82). Likewise, there was no statistically significant difference in melanoma-specific 5-year survival (78.6% versus 87.2%, p = 0.42). Conclusions: We did not find more frequent recurrence, shorter disease-free survival, or poorer melanoma-specific survival in patients with drainage to PSLN. Our findings strengthen the evidence that PSLNs should not be routinely biopsied if they are not the first-tier nodes.
Yifei Sanjie Formula or Placebo With Anlotinib as Second-Line or Above Treatment for Metastatic Non-Small-Cell Lung Cancer: Study Protocol for a Double-Blind, Placebo-Controlled Randomized Pilot Study
Authors: Chen Wenmin , Lin Jietao , Yang Ting , xin Zhang Ze , Tao Lanting , Xiao Zhiwei , Chen Hanrui , Qi Xiangjun , Sun Lingling , Cao Yang , Lin Lizhu 
Published: January 2023

Background: Anlotinib is used as a third-line treatment for advanced non-small-cell lung cancer (NSCLC), but has limited clinical benefits and several side effects, such as diarrhea and acneiform skin rash. Traditional Chinese Medicine (TCM) is commonly used to treat cancers in China. Chinese herbal medicines may have the potential as adjuvant therapies to reduce toxicity and improve the efficacy of treatments for NSCLC. Given the positive outcomes of basic research, we plan to evaluate whether the addition of the Chinese herbal medicine Yifei Sanjie formula (YFSJF) to anlotinib can improve the progression-free survival (PFS) of advanced NSCLC patients. Methods: A multicenter, randomized, double-blind, placebo-controlled parallel-group controlled pilot trial will be performed. Forty eligible patients will be randomized in a ratio of 1:1 to the intervention (YFSJF + anlotinib) and control (placebo + anlotinib) groups. Participants will be advised to take 12 mg/day of anlotinib on days 1 to 14 of each 21-day cycle. YFSJF or placebo will be administered (15 g twice daily) during each cycle until progression of disease (PD). The primary outcome will be progression-free survival (PFS), and the secondary outcomes will be overall survival (OS), the objective response rate (ORR), and patient-reported outcomes (PRO). Tumors will be assessed based on RECIST v. 1.1 after every 2 cycles of treatment. The M. D. Anderson Symptom Inventory-Lung Cancer (MDASI-LC) will be used to evaluate PRO at baseline and weekly thereafter until PD. Discussion: This will be the first trial to evaluate the effectiveness and safety of TCM combined with anlotinib for the treatment of NSCLC. The results of this randomized controlled trial will fill a gap in the research by showing whether YFSJF combined with anlotinib can improve PFS in NSCLC patients. Trial Registration: The study was registered on June 8th, 2021 on Chinese Clinical Registry; registration number ChiCTR2100047143. ( https://www.chictr.org.cn/index.aspx ). Ethics and Dissemination: The Ethics Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine approved the study protocol (approval no.: K2020151, 2021/08/19). The study will also be supervised and managed by the Ethics Committee.
Natalizumab in cerebrospinal fluid and breastmilk of patients with multiple sclerosis
Authors: Callegari Ilaria , Schneider Mika , Aebischer Vera , Voortman Margarete M. , Proschmann Undine , Ziemssen Tjalf , Lindberg Raija , Fischer-Barnicol Bettina , Khalil Michael , Kappos Ludwig , Kuhle Jens , Sanderson Nicholas S.R. , Derfuss Tobias 
Published: January 2023

Background: Natalizumab is a highly effective monoclonal antibody for the treatment of multiple sclerosis (MS), which can diffuse in different anatomical compartments, including cerebrospinal fluid (CSF) and milk. Objectives: Starting from incidental detection of natalizumab in the CSF of MS patients, the objective of this study was to develope a flow-cytometry-based assay and apply it to quantify natalizumab in body fluids, including milk collected from nursing patients over 180 days and in patients with neutralizing antibodies against natalizumab. Methods: CSF, milk and sera samples from patients with multiple sclerosis were tested by flow-cytometry for binding to a VLA-4 expressing cell line or to a control cell line. A standard curve was prepared by incubating the same cells with natalizumab at 50 μg/ml and serially diluted to 0.005 ng/ml. Binding specificity was confirmed using an anti-natalizumab neutralizing antibody. Results: Our assay was sensitive enough to detect natalizumab in CSF, with a lower detection limit of 1.5 ng/ml. Neutralizing antibodies against natalizumab inhibited binding to the cell line. In breastmilk, the peak concentration was observed during the first 2 weeks after infusion and the average concentration over the observation time was 173.3 ng/ml, with a trend toward increased average milk concentration over subsequent administrations. Conclusion: Routine use of such an assay would enable a better understanding of the safety of therapeutic antibody administration during pregnancy and lactation.
Pretreatment findings on magnetic resonance imaging in primary central nervous system lymphoma may predict overall survival duration
Authors: Huntoon Kristin , Makary Mina S , Shah Varun S , Aquino Anthony , Pandya Vijay , Giglio Pierre , Slone H Wayne , Elder J Bradley 
Published: January 2023

Background and purpose: Primary central nervous system lymphoma (PCNSL) lesions often show avid contrast enhancement on T1-weighted contrast-enhanced MRI sequences. However, several case reports and a clinical study have described PCNSL in patients with no contrast enhancement on MRI. We assessed whether overall survival (OS) time was related to any tumor characteristics (lesion location, volume, and number; contrast enhancement; necrosis; proximity to the subarachnoid space; and edema) on MRI in patients with PCNSL. Materials and Methods We retrospectively reviewed records (MRI features, pathology, and survival data) of all patients at our institution with PCNSL who had been seen from, 2007 through 2017, and had undergone pretreatment MRI. Results We identified 79 patients (42 men, 37 women) with a mean age at diagnosis of 61.7 ± 10.4 years. The mean OS duration was 44.6 ± 41.7 months. The most common pathological diagnosis (74 patients) was diffuse large B-cell lymphoma. No associations were found between OS time and lesion location, volume, and number; contrast enhancement; necrosis; proximity to the subarachnoid space; or edema. However, a sole patient with non-enhancing PCNSL on MRI was found to have low-grade disease, with prolonged survival (>83 months). Several other patients with leptomeningeal disease had a mean OS time of 80 months. Patients with hemorrhagic lesions had a mean OS of 25.5 months. Conclusions The survival time for patients with PCNSL may be longer than previously thought, especially for patients with leptomeningeal seeding and lesions with hemorrhagic components Also, non-enhancing tumors may be less aggressive than enhancing tumors.
Incidence of Allergic Drug Eruption due to Cotrimoxazole in HIV-Positive Individuals with CD4 ≤200 Cells/ul
Authors: Rosali Irene , Virgayanti Putu Siska , Marta Della Sabrina , Danudirgo Emon Winardi , Hadinata Sisca 
Published: January 2023

Allergic drug eruptions (ADE) remain a challenge in people living with HIV (PLWH), requiring more studies to guide clinical approaches. While cotrimoxazole is widely used as prophylaxis in PLWH, relationship between client characteristics toward the occurrence of cotrimoxazole ADEs is still poorly understood. A retrospective cohort study followed PLWH initiated with antiretroviral therapy (ART) in St. Carolus Hospital between January 2009 to December 2021. ADE occurrence due to cotrimoxazole were tested for significance using Pearson's Chi-square and Fisher's Exact Test (significant outcome measured as p < 0.05) against CD4 levels at very low (0-100 cells/ul) and low (101-200 cells/ul) groups, comorbidities, and retention status. Cotrimoxazole-related ADEs occurred in 258 (14%) of 1789 subjects with CD4 levels ≤200 cells/ul. Comorbidities of Hepatitis B, Hepatitis C, and M. tuberculosis infections were found in 11, 4, and 95 subjects respectively. 151 (59%) of ADE group had very low CD4 levels (p value  > 0.05). No significant difference was found in ADE incidence between age groups, genders, CD4 levels, comorbidities, and ART retention. Cotrimoxazole-induced ADE is unrelated to CD4 levels, and ART retention was not affected. ADE severity ranges from mild to serious manifestations, and close monitoring is crucial to ensure ADEs are treated ART are well-maintained.
Foreign Trade, Human Capital and Economic Growth in India under the Liberalised Trade Regime
Authors: Maitra Biswajit , Chakraborty Moutushi 
Published: January 2023

This study revisits trade–growth dynamics in India augmenting the role of human capital for the liberalised trade regime. The autoregressive distributed lag-bounds testing approach finds cointegrating relation of income with the different combinations of export, import, exchange rate, trade openness, education and health dimension of human capital. The long-run and short-run dynamics of such relations confirm that both export and import enhance income growth that testifies export-led and import-led growth premises. Trade openness proves detrimental to growth, while human capital spurs growth. However, the growth gains from the human capital vary across alternative measures of human capital. A battery of diagnostic tests corroborates these inferences robustly. Policy manifestation for trade promotion might be beneficial for higher economic growth in India. JEL Codes: F43, F13, F14, O24
Prediction of persistent chronic cough in patients with chronic cough using machine learning
Authors: Chen Wansu , Schatz Michael , Zhou Yichen , Xie Fagen , Bali Vishal , Das Amar , Schelfhout Jonathan , Stern Julie A. , Zeiger Robert S. 
Published: January 2023

IntroductionThe aim of this study was to develop and validate prediction models for risk of persistent chronic cough (PCC) in patients with chronic cough (CC). This was a retrospective cohort study.MethodsTwo retrospective cohorts of patients 18–85 years of age were identified for years 2011–2016: a specialist cohort which included CC patients diagnosed by specialists, and an event cohort which comprised CC patients identified by at least three cough events. A cough event could be a cough diagnosis, dispensing of cough medication or any indication of cough in clinical notes. Model training and validation were conducted using two machine-learning approaches and 400+ features. Sensitivity analyses were also conducted. PCC was defined as a CC diagnosis or any two (specialist cohort) or three (event cohort) cough events in year 2 and again in year 3 after the index date.Results8581 and 52 010 patients met the eligibility criteria for the specialist and event cohorts (mean age 60.0 and 55.5 years), respectively. 38.2% and 12.4% of patients in the specialist and event cohorts, respectively, developed PCC. The utilisation-based models were mainly based on baseline healthcare utilisations associated with CC or respiratory diseases, while the diagnosis-based models incorporated traditional parameters including age, asthma, pulmonary fibrosis, obstructive pulmonary disease, gastro-oesophageal reflux, hypertension and bronchiectasis. All final models were parsimonious (five to seven predictors) and moderately accurate (area under the curve: 0.74–0.76 for utilisation-based models and 0.71 for diagnosis-based models).ConclusionsThe application of our risk prediction models may be used to identify high-risk PCC patients at any stage of the clinical testing/evaluation to facilitate decision making.
Phenotyping empyema by pleural fluid culture results and macroscopic appearance: an 8-year retrospective study
Authors: Chan Ka Pang , Ng Susanna So Shan , Ling Kwun Cheung , Ng Ka Ching , Lo Lai Ping , Yip Wing Ho , Ngai Jenny Chun Li , To Kin Wang , Ko Fanny Wai San , Lee Yun Chor Gary , Hui David Shu Cheong 
Published: January 2023

BackgroundThe clinical impact of phenotyping empyema is poorly described. This study was designed to evaluate clinical characteristics and outcomes based on the two readily available parameters, pleural fluid culture status and macroscopic fluid appearance.MethodsA retrospective study was conducted on patients with empyema hospitalised between 2013 and 2020. Empyema was classified into culture-positive empyema (CPE) or culture-negative empyema (CNE) and pus-appearing empyema (PAE) or non-pus-appearing empyema (non-PAE) based on the pleural fluid culture status and macroscopic fluid appearance, respectively.ResultsAltogether, 212 patients had confirmed empyema (CPE: n=188, CNE: n=24; PAE: n=118, non-PAE: n=94). The cohort was predominantly male (n=163, 76.9%) with a mean age of 65.0±13.6 years. Most patients (n=180, 84.9%) had at least one comorbidity. Patients with CPE had higher rates of in-hospital mortality (19.1%versus0.0%, p=0.017) and 90-day mortality (18.6%versus0.0%, p=0.017) and more extrapulmonary sources of infection (29.8%versus8.3%, p=0.026) when compared with patients with CNE. No significant difference in mortality rate was found between PAE and non-PAE during the in-hospital stay and at 30 days and 90 days. Patients with PAE had less extrapulmonary sources of infection (20.3%versus36.2%, p=0.010) and more anaerobic infection (40.9%versus24.5%, p=0.017) than those with non-PAE. The median RAPID (renal, age, purulence, infection source, and dietary factors) scores were higher in the CPE and non-PAE groups. After adjusting for covariates, culture positivity was not independently associated with mortality on multivariable analysis.ConclusionEmpyema is a heterogeneous disease with different clinical characteristics. Phenotyping empyema into different subclasses based on pleural fluid microbiological results and macroscopic fluid appearance provides insight into the underlying bacteriology, source of infection and subsequent clinical outcomes.
Clinical response to benralizumab can be predicted by combining clinical outcomes at 3 months with baseline characteristics
Authors: Kroes Johannes A. , de Jong Kim , Hashimoto Simone , Zielhuis Sander W. , van Roon Eric N. , Sont Jacob K. , ten Brinke Anneke 
Published: January 2023

BackgroundBenralizumab is highly effective in many, but not all, patients with severe asthma. Baseline characteristics alone are insufficient to predict an individual's probability of long-term benralizumab response. The objectives of the present study were to: 1) study whether parameters at 3 months, in addition to baseline characteristics, contribute to the prediction of benralizumab response at 1 year; and 2) develop an easy-to-use prediction tool to assess an individual's probability of long-term response.MethodsWe assessed the effect of benralizumab treatment in 192 patients from the Dutch severe asthma registry (RAPSODI). To investigate predictors of long-term benralizumab response (≥50% reduction in maintenance oral corticosteroid (OCS) dose or annual exacerbation frequency) we used logistic regression, including baseline characteristics and 3-month Asthma Control Questionnaire (ACQ-6) score and maintenance OCS dose.ResultsBenralizumab treatment significantly improved several clinical outcomes, and 144 (75%) patients were classified as long-term responders. Response prediction improved significantly when 3-month outcomes were added to a predictive model with baseline characteristics only (area under the receiver-operating characteristic (AUROC) 0.85versus0.72, p=0.001). Based on this model, a prediction tool using sex, prior biologic use, baseline blood eosinophils, forced expiratory volume in 1 s, and at 3 months OCS dose and ACQ-6 was developed which classified patients into three categories with increasing probability of long-term response (95% CI): 25% (3–65%), 67% (57–77%) and 97% (91–99%), respectively.ConclusionIn addition to baseline characteristics, treatment outcomes at 3 months contribute to the prediction of benralizumab response at 1 year in patients with severe eosinophilic asthma. Prediction tools as proposed in this study may help physicians optimise the use of costly biologics.
Hyperoxia improves exercise capacity in cardiopulmonary disease: a series of randomised controlled trials
Authors: Müller Julian , Lichtblau Mona , Saxer Stéphanie , Schneider Simon R. , Appenzeller Paula , Bauer Meret , Hasler Elisabeth D. , Schwarz Esther I. , Bloch Konrad E. , Ulrich Silvia 
Published: January 2023

Background

The aim of this study was to investigate the overall and differential effect of breathing hyperoxia (inspiratory oxygen fraction (
F

IO
2

) 0.5)
versus
placebo (ambient air,
F

IO
2

0.21) to enhance exercise performance in healthy people, patients with pulmonary vascular disease (PVD) with precapillary pulmonary hypertension (PH), COPD, PH due to heart failure with preserved ejection fraction (HFpEF) and cyanotic congenital heart disease (CHD) using data from five randomised controlled trials performed with identical protocols.

Methods

91 subjects (32 healthy, 22 with PVD with pulmonary arterial or distal chronic thromboembolic PH, 20 with COPD, 10 with PH in HFpEF and seven with CHD) performed two cycle incremental (IET) and two constant work-rate exercise tests (CWRET) at 75% of maximal load (W
max
), each with ambient air and hyperoxia in single-blinded, randomised, controlled, crossover trials. The main outcomes were differences in W
max
(IET) and cycling time (CWRET) with hyperoxia
versus
ambient air.

Results

Overall, hyperoxia increased W
max
by +12 W (95% CI: 9–16, p<0.001) and cycling time by +6:13 min (4:50–7:35, p<0.001), with improvements being highest in patients with PVD (W
max
/min: +18%/+118%
versus
COPD: +8%/+60%, healthy: +5%/+44%, HFpEF: +6%/+28%, CHD: +9%/+14%).

Conclusion
This large sample of healthy subjects and patients with various cardiopulmonary diseases confirms that hyperoxia significantly prolongs cycling exercise with improvements being highest in endurance CWRET and patients with PVD. These results call for studies investigating optimal oxygen levels to prolong exercise time and effects on training.
Adding a biologic to allergen immunotherapy increases treatment efficacy
Authors: Bożek Andrzej , Fischer Andreas , Bogacz-Piaseczynska Agnieszka , Canonica Giorgio Walter 
Published: January 2023

BackgroundThe application of allergen immunotherapy (AIT) in combination with biological agents has been found to increase both the safety and efficacy of the desensitisation procedure in patients with food and insect venom allergy. The aim of our study was to compare the effectiveness of AIT in patients with house dust mite (HDM)-driven asthma treated with and without omalizumab.Materials and methodsThe study was a placebo-controlled, three-armed, randomised, parallel-group, multicentre trial that included 52 patients with HDM-driven asthma. Only patients with monosensitisation to HDM were included. The study compared three patterns of therapy: omalizumab alone, HDM subcutaneous immunotherapy (SCIT-HDM)+ omalizumab, and SCIT alone. The main outcomes were evaluate the Asthma Control Questionnaire (ACQ) score, number of asthma exacerbations and reduction in the daily dose of inhaled steroids during 12 months of observation.ResultsAll variants of therapy led to significantly improved ACQ scores and reduction of asthma exacerbations in all study groups after 12 months of treatment. A statistically significant reduction in the daily doses of inhaled corticosteroids in the group with omalizumab alone (650±150 µgversus500±50 µg for p=0.003) or SCIT-HDM+omalizumab (550±250 µgversus375±75 µg for p=0.001) was observed, favouring the latter group.ConclusionThe efficacy of AIT for HDM-driven asthma is significantly increased by the combination of allergen vaccine with omalizumab.
Inhaled formoterol impairs aerobic exercise capacity in endurance-trained individuals: a randomised controlled trial
Authors: Jessen Søren , Lemminger Anders , Backer Vibeke , Fischer Mads , Di Credico Andrea , Breenfeldt Andersen Andreas , Bangsbo Jens , Hostrup Morten 
Published: January 2023

BackgroundThe 2022 Global Initiative for Asthma guidelines emphasise the inhaled long-acting β2-agonist formoterol as part of the first treatment step, and therefore formoterol use among athletes will probably increase. However, prolonged supratherapeutic use of inhaled β2-agonists impairs training outcomes in moderately trained men. We investigated whether inhaled formoterol, at therapeutic doses, imposes detrimental effects in endurance-trained individuals of both sexes.Methods51 endurance-trained participants (31 male, 20 female; mean±sdmaximal oxygen consumption (V̇O2max) 62±6 mL·min−1·kg bw−1and 52±5 mL·min−1·kg bw−1, respectively) inhaled formoterol (24 µg; n=26) or placebo (n=25) twice daily for 6 weeks. At baseline and follow-up, we assessedV̇O2maxand incremental exercise performance during a bike-ergometer ramp-test; body composition by dual-energy X-ray absorptiometry; muscle oxidative capacity by high-resolution mitochondrial respirometry, enzymatic activity assays and immunoblotting; intravascular volumes by carbon monoxide rebreathing; and cardiac left ventricle mass and function by echocardiography.ResultsCompared to placebo, formoterol increased lean body mass by 0.7 kg (95% CI 0.2–1.2 kg; treatment×trial p=0.022), but decreasedV̇O2maxby 5% (treatment×trial p=0.013) and incremental exercise performance by 3% (treatment×trial p<0.001). In addition, formoterol lowered muscle citrate synthase activity by 15% (treatment×trial p=0.063), mitochondrial complex II and III content (treatment×trial p=0.028 and p=0.007, respectively), and maximal mitochondrial respiration through complexes I and I+II by 14% and 16% (treatment×trial p=0.044 and p=0.017, respectively). No apparent changes were observed in cardiac parameters and intravascular blood volumes. All effects were sex-independent.ConclusionOur findings demonstrate that inhaled therapeutic doses of formoterol impair aerobic exercise capacity in endurance-trained individuals, which is in part related to impaired muscle mitochondrial oxidative capacity. Thus, if low-dose formoterol fails to control respiratory symptoms in asthmatic athletes, physicians may consider alternative treatment options.