bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the response to platinum-based chemotherapy on the second-line immune checkpoint inhibitor monotherapy in non-small cell lung cancer with PD-L1 expression ≤49%: a multicenter retrospective study
Authors: Yoshimura Akihiro , Takeda Takayuki , Kataoka Nobutaka , Tanimura Keiko , Fukui Mototaka , Chihara Yusuke , Takei Shota , Kawachi Hayato , Nakanishi Kentaro , Yamanaka Yuta , Tamiya Nobuyo , Honda Ryoichi , Okura Naoko , Yamada Takahiro , Uryu Kiyoaki , Murai Junji , Shiotsu Shinsuke , Yoshioka Hiroshige , Yamada Tadaaki , Kurata Takayasu , Takayama Koichi 
Published: January 2024

IntroductionThe efficacy of second-line immune checkpoint inhibitor (ICI) therapy is limited in non-small cell lung cancer (NSCLC) patients with ≤ 49% PD-L1 expression. Although chemoimmunotherapy is a promising strategy, platinum-based chemotherapy followed by ICI monotherapy is often used to avoid synergistic adverse events. However, predictors of the efficacy of ICI monotherapy after platinum-based chemotherapy in NSCLC with ≤ 49% PD-L1 expression remain scarce.MethodsThis multicenter retrospective study evaluated 54 advanced or recurrent NSCLC patients with ≤ 49% PD-L1 expression who were treated with second-line ICI monotherapy following disease progression on first-line platinum-based chemotherapy at nine hospitals in Japan. The impact of response to platinum-based chemotherapy on the efficacy of subsequent ICI monotherapy was investigated.ResultsThe response to first-line platinum-based chemotherapy was divided into two groups: the non-progressive disease (PD) group, which included patients who did not experience disease progression after four cycles of chemotherapy, and the PD group, which included patients who showed initial PD or could not maintain disease control during the four cycles of chemotherapy and switched to second-line ICI monotherapy. Among the 54 patients, 32 and 22 were classified into the non-PD and PD groups, respectively. The non-PD group showed better response rates (p = 0.038) and longer overall survival (OS) with ICI monotherapy (p = 0.023) than the PD group. Multivariate analysis identified that maintaining a non-PD status after four cycles of chemotherapy was an independent prognostic factor for ICI monotherapy (p = 0.046). Moreover, patients with a modified Glasgow Prognostic Score (mGPS) of 0 showed a tendency for longer OS with ICI monotherapy (p = 0.079), and there was a significant correlation between maintaining non-PD after four cycles of chemotherapy and an mGPS of 0 (p = 0.045).ConclusionMaintaining a non-PD status after four cycles of platinum-based chemotherapy was a predictor of OS after second-line ICI monotherapy. These findings will help physicians select the most suitable treatment option for NSCLC patients who were treated with platinum-based chemotherapy and switched to second-line treatment. Those who experienced early PD during platinum-based chemotherapy should not be treated with ICI monotherapy in the second-line setting.
Cancer-associated financial burden in German head and neck cancer patients
Authors: Rast Jonas , Zebralla Veit , Dietz Andreas , Wichmann Gunnar , Wiegand Susanne 
Published: January 2024

BackgroundThe financial toxicity of cancer causes higher morbidity and mortality. As the financial burden due to head and neck cancer (HNC) in European healthcare systems with legally established compulsory health insurance is still poorly understood, we set up an investigation to assess the financial impact of HNC.MethodsBetween August 2022 and March 2023, HNC consecutive patients (n = 209) attending the cancer aftercare program of a university hospital in an outpatient setting were surveyed utilizing self-administered questionnaires about their socioeconomic situation, income loss, and out-of-pocket payments (OOPPs).ResultsThe majority of HNC patients (n = 119, 59.5%) reported significant financial burden as a consequence of OOPP (n = 100, 50.0%) and/or income loss (n = 51, 25.5%). HNC patients reporting financial burden due to OOPP had on average 1,716 € per year costs related to their disease, whereas patients reporting an income loss had a mean monthly income loss of 620.53 €. Advanced UICC (7th edition, 2017) stage, T3 or T4 category, and larynx/hypopharynx cancer are significant predictors of financial burden.ConclusionHNC survivors suffer from significant financial burden after HNC treatment, even in Germany with a healthcare system with statutory health insurance. The findings from this study offer valuable insights for healthcare professionals and policymakers, helping them acknowledge the economic impact of HNC.
Effective treatment of advanced lung adenocarcinoma with paraneoplastic leukemoid reaction with Lorlatinib: a case report
Authors: Niu Ruiqi , Zhang Yiruo , Pang Jingdan , Zhou Qing , Lei Yu , Du Yingying 
Published: January 2024

BackgroundLorlatinib is a new generation ALK kinase inhibitor. We describe a 52-year-old patient with ALK-positive advanced lung adenocarcinoma who achieved remission after multi-line therapy combined with paraneoplastic leukemoid reaction treated with Lorlatinib.Case reportA 52-year-old male patient was diagnosed with stage IV right lung adenocarcinoma, ALK: (+), previously received oral Crizotinib and Alectinib. Blood routine showed white blood cells abnormally elevated after disease progression, and maximum white blood cell count was 179.14×10^9/L. The patient was enrolled in study entitled “a phase II, multicenter, open-label, dual-cohort study to evaluate the efficacy and safety of LORLATINIB monotherapy in ALK inhibitor-treated locally advanced or metastatic ALK-positive non-small cell lung cancer patients in China”. With oral Lorlatinib, the white blood cell count decreased from 179.14×10^9/L to normal after two weeks of administration. PFS was 4.5 months. When follow up imaging showed lesions progression, the white blood cell count increased again, diagnosing a paraneoplastic leukemic reaction. OS was 5.2 months.ConclusionIn this case, fourth-line Lorlatinib treatment is effiective in ALK-positive advanced patient with paraneoplastic leukemoid reaction. ClinicalTrials.gov Identifier: NCT03909971
Diagnostic validity of p16, E-cadherin, cyclin D1, p53, and HPV E6/E7 mRNA in CIN 3-like squamous cell carcinoma of the cervix
Authors: Xing Zhao , Danhua Shen , Xiaobo Zhang 
Published: January 2024

ObjectiveCervical intraepithelial neoplasia grade 3 (CIN 3)-like SCC is a recently identified deceptive growth pattern that closely mimics endocervical crypt involvement by CIN 3. As CIN 3-like SCC is indistinguishable from endocervical crypt involvement by CIN 3, it poses a significant challenge for pathologists.MethodWe examined 23 cases of CIN 3-like SCC, 6 of which also had concomitant conventional invasive SCC, and 9 cases of endocervical crypt involvement by CIN 3 as a control group. Immunohistochemistry was used to investigate the expression of p16, E-cadherin, cyclin D1, and p53, and the expression of human papillomavirus (HPV) E6/E7 mRNA, the key virus carcinogen of HPV, was detected. The clinicopathological, immunohistochemical, and molecular characteristics of endocervical crypt involvement by CIN 3, CIN 3-like SCC, and the concomitant conventional invasive SCC element were examined.ResultCIN 3-like SCC exhibited a characteristic morphology similar to endocervical crypt involvement by CIN 3, with pushing borders invading into the wall of the cervix, often to a significant depth in most cases. Immunophenotypic features of E-cadherin, p16, cyclin D1, and p53 differed between CIN 3-like SCC and conventional invasive SCC, both in staining intensity and region. E6/E7 mRNA expression was higher in CIN 3-like SCC than in endocervical crypt involvement by CIN 3 (P &lt; 0.05).ConclusionCIN 3-like SCC is the type of cancer, presenting numerous challenges and potential for confusion as it mimics the phenotypes of endocervical crypt involvement by CIN 3.
Magnitude and its associated factors of neonatal jaundice among neonates admitted to the neonatal intensive care unit of Dessie Town public hospitals, Amhara region, Ethiopia, 2020: a multicenter cross-sectional study
Authors: Tessema Mohammed , Mekonnen Hussen , Alemu Tsion , Godie Yohannes , Teklehaimanot Wegayehu Zeneb , Mengstie Leweyehu Alemaw 
Published: January 2024

BackgroundNeonatal jaundice is a prevalent illness affecting approximately 60%–80% of newborns. In severe cases, it can result in severe neurological distress. Approximately 1.1 million neonates are affected annually on a global scale, with the vast majority living in sub-Saharan Africa and southern Asia. It is common in newborns in the first week of life. This study aims to assess the magnitude and determinants of jaundice in newborns admitted to the neonatal intensive care unit (NICU) of public hospitals in the city of Dessie in northern Ethiopia.MethodsAn institutional cross-sectional study was conducted at the NICU at Dessie town public hospitals from 30 March to 30 April 2020. A systematic random sampling procedure was used to select the study participants. Data were collected through face-to-face interviews with mothers using a structured questionnaire and by reviewing neonatal medical records using a checklist. Binary logistic regression analysis was used to identify the determinants of neonatal jaundice. A significance level of less than 0.05 was used to declare the statistical significance in the final model.ResultsA total of 218 neonates with their mothers were included in the study. The prevalence rate of neonatal jaundice was found to be 28.4%. The major associated factors for neonatal jaundice were sepsis [adjusted odds ratio (AOR): 10.13, 95% confidence interval (CI) = 2.36, 43.56], preterm &lt; 37 weeks (AOR: 6.03, 95% CI = 1.41, 25.79) low APGAR score &lt; 7 (AOR: 7.34, 95% CI = 1.34, 39.65), ABO incompatibility (AOR: 24.55 95% CI = 1.58, 68.83), prolonged labor (AOR 9.03, 95% CI = 1.67, 48.33), and Rh incompatibility (AOR = 30.40, 95% CI = 2.01, 66.20).ConclusionThe magnitude of neonatal jaundice among neonates was determined to be high. Therefore, both maternal and neonatal factors contributed significantly to the management of neonatal jaundice and also influenced the use of phototherapy treatment. Proper consideration of these factors is crucial for the prevention and treatment of neonatal jaundice.
Exploration of biomarkers for efficacy evaluation of traditional Chinese medicine syndromes of acute exacerbation of chronic obstructive pulmonary disease based on metabolomics
Authors: Hailong Zhang , Yimei Si , Yan Du , Xinguang Liu , Jiansheng Li 
Published: January 2024

Background: Traditional Chinese medicine (TCM) is effective for the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD); however, there is no objective index for the evaluation of TCM syndrome efficacy. This study aimed to screen biomarkers related to the efficacy of TCM syndrome using metabolomics.Methods: We recruited AECOPD patients with phlegm-heat congesting lung (PH)/phlegm-damp amassing lung (PD) syndrome and treated them with Chinese herbal medicine (Qingre Huatan or Zaoshi Huatan granules) in addition to conventional medicine for 7 days. Data on clinical symptoms and sign scores, modified British Medical Research Council (mMRC), COPD assessment test (CAT), and inflammation indicators, including white blood cell (WBC) count, percentage of neutrophil count (NEU%), and C-reactive protein (CRP), were collected before and after treatment to evaluate the therapeutic effect. Serum samples were collected before and after treatment for metabolomic analysis to screen differential metabolites.Results: A total of 69 patients with AECOPD were enrolled, including 41 and 28 patients in the PH and PD groups, respectively. The clinical symptoms and sign scores, CAT, mMRC, NEU%, and CRP levels after treatment were lower than those before treatment in both groups (p &lt; 0.05). Serum metabolomics analysis showed that there were 13 differential metabolites in the PH group and 16 differential metabolites in the PD group before and after treatment (p &lt; 0.05, variable importance projection (VIP) ≥ 1.00). In the PH group, lysophosphatidylcholine (LPC) (16:0), LPC (17:1), LPC (18:3), LPC (18:2), and LPC (17:0) negatively correlated with clinical symptoms and sign scores (p &lt; 0.05); LPC (16:0), LPC (17:1), LPC (16:1), and LPC (17:0) negatively correlated with WBC (p &lt; 0.05) and NEU% (p &lt; 0.05); and LPC (16:0) negatively correlated with CRP levels. In the PD group, L-phenylalanine positively correlated with CRP levels (p &lt; 0.05), and 2-methylbutyroylcarnitine positively correlated with clinical symptoms and sign (p &lt; 0.05) and CAT scores (p &lt; 0.05). DL-carnitine positively correlated with clinical symptoms and sign scores (p &lt; 0.05).Conclusion: Serum metabolites may be potential indicators to objectively evaluate the efficacy of TCM syndromes; however, further large controlled trials are required to verify these findings.
Pharmacokinetics, pharmacodynamics and safety of 15 mg-tolvaptan administered orally for 7 consecutive days to Chinese patients with child-Pugh B cirrhosis
Authors: Liu Hongzhong , Wang Yongfeng , Liu Tao , Chen Yingxuan , Zheng Xin , Liu Ming , Zhao Qian , Zeng Minde , Jiang Ji , Mao Yimin , Hu Pei 
Published: January 2024

Background: Tolvaptan, a selective vasopressin V2-receptor antagonist, can elicit a diuretic effect without significant electrolyte loss. The aims were to evaluate multiple-dose pharmacokinetics, pharmacodynamics and safety of daily administration of 15 mg tolvaptan in Chinese adult patients with confirmed Child-Pugh Class B cirrhosis accompanied by ascites.Methods: This was an open-label, single-center, single- and multiple-dose study. All patients received a daily 15 mg dose of tolvaptan for 7 consecutive days. The plasma concentrations of tolvaptan and its two metabolites (DM-4103, DM-4107) were measured using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). In addition, various pharmacokinetics parameters were calculated. The pharmacodynamic outcomes evaluated changes in serum sodium and potassium concentrations, daily urine volume, daily water consumption, fluid balance and body weight. Safety profiles, including the incidence of treatment-emergent adverse events (TEAEs), were carefully recorded.Results: Eleven patients with Child-Pugh B cirrhosis were eventually enrolled in the study. Plasma concentrations of tolvaptan and DM-4107 reached steady-states after 7 days of consecutive oral administration. No accumulation of tolvaptan or DM-4107 was found, but DM-4103 accumulated 18.2-fold after multiple-dosing. The daily urine volume and daily water consumption were statistically significantly increased after administration of tolvaptan from Day 1 to Day 7 (all p &lt; 0.05), accompanied by an increased serum sodium concentration. Of 11 patients, 9 (81.8%) reported 20 TEAEs, with the majority being mild to moderate in severity. The most commonly occurring TEAEs were thirst (45.5%), pollakiuria (36.4%) and dry mouth (27.3%).Conclusion: Tolvaptan at a daily dose of 15 mg had a diuretic effect but did not increase serum sodium excretion or lead to tolvaptan accumulation. It is therefore can be safely used for short-term treatment of Chinese adult patients with confirmed Child-Pugh B cirrhosis.Clinical Trial Registration:https://clinicaltrials.gov/search?term=NCT01359462, identifier NCT01359462.
Surgical procedure of intratympanic injection and inner ear pharmacokinetics simulation in domestic pigs
Authors: Moatti Adele , Connard Shannon , De Britto Novietta , Dunn William A. , Rastogi Srishti , Rai Mani , Schnabel Lauren V. , Ligler Frances S. , Hutson Kendall A. , Fitzpatrick Douglas C. , Salt Alec , Zdanski Carlton J. , Greenbaum Alon 
Published: January 2024

Introduction: One major obstacle in validating drugs for the treatment or prevention of hearing loss is the limited data available on the distribution and concentration of drugs in the human inner ear. Although small animal models offer some insights into inner ear pharmacokinetics, their smaller organ size and different barrier (round window membrane) permeabilities compared to humans can complicate study interpretation. Therefore, developing a reliable large animal model for inner ear drug delivery is crucial. The inner and middle ear anatomy of domestic pigs closely resembles that of humans, making them promising candidates for studying inner ear pharmacokinetics. However, unlike humans, the anatomical orientation and tortuosity of the porcine external ear canal frustrates local drug delivery to the inner ear.Methods: In this study, we developed a surgical technique to access the tympanic membrane of pigs. To assess hearing pre- and post-surgery, auditory brainstem responses to click and pure tones were measured. Additionally, we performed 3D segmentation of the porcine inner ear images and used this data to simulate the diffusion of dexamethasone within the inner ear through fluid simulation software (FluidSim).Results: We have successfully delivered dexamethasone and dexamethasone sodium phosphate to the porcine inner ear via the intratympanic injection. The recorded auditory brainstem measurements revealed no adverse effects on hearing thresholds attributable to the surgery. We have also simulated the diffusion rates for dexamethasone and dexamethasone sodium phosphate into the porcine inner ear and confirmed the accuracy of the simulations using in-vivo data.Discussion: We have developed and characterized a method for conducting pharmacokinetic studies of the inner ear using pigs. This animal model closely mirrors the size of the human cochlea and the thickness of its barriers. The diffusion time and drug concentrations we reported align closely with the limited data available from human studies. Therefore, we have demonstrated the potential of using pigs as a large animal model for studying inner ear pharmacokinetics.
Adherence to exercise after an acute coronary syndrome: a 6-month randomized controlled trial
Authors: Saarikoski Essi O. , Roiha Elina T. M. , Kiviniemi Antti M. , Cerdán-De-las-Heras Jose , Perkiömäki Juha , Kaikkonen Kari S. , Tulppo Mikko P. 
Published: January 2024

Introduction: Exercise training with well-known health benefits is a key element in the self-management of coronary artery disease (CAD). Although current guidelines for patients with CAD recommend daily exercise training, most of the patients do not follow the guidelines. We tested the hypothesis that an exercise training program guided by a novel technology used at home will improve adherence to exercise training.Methods: One to three weeks after percutaneous coronary intervention (PCI), acute coronary syndrome patients (n = 50) were randomized into traditional (age 65 ± 8 years) and novel technology-guided (age 60 ± 8 years) exercise rehabilitation groups. The novel technology included a tablet computer with a virtual autonomous physiotherapy agent (VAPA group) for every patient at home; it was used to guide exercise training time, volume, and intensity. Traditional rehabilitation was performed by exercise training prescriptions, phone calls, and diaries (control group). The duration of the rehabilitation program was 6 months for both groups. Exercise capacity and 24-h heart rate variability were measured at baseline and at the end of the program. Adherence to exercise was measured over 6 months as the percentage of realized training.Results: None of the patients dropped out from the VAPA group, while three patients dropped out from the control group. Adherence to exercise was higher in the VAPA group than in the control group for resistance training (141% ± 56% vs. 50% ± 20%, p &lt; 0.0001), and there were no differences between the groups for aerobic training (144% ± 45% vs. 119% ± 65%, p = 0.22). Exercise capacity increased in both the groups (time p &lt; 0.001, time × group interaction p = ns). High-frequency power of R-R intervals (lnHF) increased in the VAPA group but remained unchanged in the control group (natural logarithm of lnHF power from 5.5 ± 0.7 to 5.8 ± 0.9 ms2 and from 5.3 ± 0.8 to 5.2 ± 0.7 ms2, respectively, time × group interaction p = 0.014).Conclusion: Compared with the use of traditional methods, the use of novel technology at home results in better adherence to exercise, particularly in resistance training, in acute coronary syndrome patients. Second, the VAPA group showed improved cardiac vagal regulation, documented by increased vagally mediated R-R interval fluctuation, compared with the traditional training group (ClinicalTrials.gov identifier: NCT03704025).
Below or all the way to the peak? Oxygen uptake efficiency slope as the index of cardiorespiratory response to exercise—the NOODLE study
Authors: Kasiak Przemysław , Kowalski Tomasz , Rębiś Kinga , Klusiewicz Andrzej , Starczewski Michał , Ładyga Maria , Wiecha Szczepan , Barylski Marcin , Poliwczak Adam Rafał , Wierzbiński Piotr , Mamcarz Artur , Śliż Daniel 
Published: January 2024

Background: The ratio of oxygen uptake (VO2) to minute ventilation (VE) is described as the oxygen uptake efficiency slope (OUES). OUES has been suggested as a valuable submaximal cardiorespiratory index; however, its characteristics in endurance athletes remain unknown. In this study, we a) investigated OUES between different time intervals, b) assessed their prediction power for VO2peak, and c) derived new prediction equations for OUES tailored for well-trained individuals.Materials and Methods: A total of 77 male (age = 21.4 ± 4.8 yrs; BMI = 22.1 ± 1.6 kg·m−2; peak oxygen uptake = 4.40 ± 0.64 L·min−1) and 63 female individuals (age = 23.4 ± 4.3 yrs; BMI = 23.1 ± 1.6 kg·m−2; peak oxygen uptake = 3.21 ± 0.48 L·min−1) underwent the cycling cardiopulmonary exercise test. OUES was measured at 75%, 90%, and 100% of exercise duration. Prediction power and new models were derived with the multiple linear regression method.Results: In male subjects, OUES [mL·min−1/L·min−1] from 75% = 4.53 ± 0.90, from 90% = 4.52 ± 0.91, and from 100% = 4.41 ± 0.87. In female subjects, OUES [mL·min−1/L·min−1] from 75% = 3.50 ± 0.65, from 90% = 3.49 ± 0.62, and from 100% = 3.41 ± 0.58. OUES did not differ between time intervals in male (p = 0.65) and female individuals (p = 0.69). OUES strongly predicts peak VO2 independently from the measuring interval (β = 0.71–0.80; R2 = 0.50–0.63). The prediction model designed for elite athletes was OUES [mL·min−1/L·min−1] = −1.54 + 2.99; BSA [m2]—0.0014; (age [in years]; sex [1 = male, 2 = female]) (R2 = 0.36).Conclusion: OUES enables an accurate prediction of peak cardiorespiratory fitness in elite endurance athletes. OUES is a feasible alternative to maximal exercise testing. A new prediction equation should be used for highly trained individuals. Physicians should understand OUES physiology to properly assess the cardiorespiratory response to exercise in athletic cohorts.