Search Results (66)

Background/Objectives: Most patients with non-small cell lung cancer (NSCLC) receive chemo- and/or immunotherapy, which can be associated with adverse events including fatigue. Affected patients may not be able to receive the complete chemo- and/or immunotherapy as planned. In this context, patients may benefit from maintaining their physical activity, which can be challenging. An app reminding patients to perform a certain number of steps may have a positive effect on physical activity during chemo- and/or immunotherapy. Such an app is under development and will be tested in a prospective trial. The current APACHIE-01 study (NCT06993896) is required for proper sample size calculation and design of the planned trial. Methods: The main goal of the APACHIE-01 study is to evaluate patterns and predictors of physical activity during chemo- and/or immunotherapy for locally advanced or metastatic NSCLC. The primary endpoint is the assessment of the mean number of steps per week during the first three cycles of chemo- and/or immunotherapy for lung cancer. The baseline value is represented by the mean number of steps during the last week prior to chemotherapy and/or immunotherapy. Secondary endpoints include associations between mean number of steps per week and a pain score, a distress score, and a fatigue score. The recruitment of the required 38 patients should be completed within 4 months and the treatment period will be 9–10 weeks (three cycles of chemo- and/or immunotherapy), resulting in a total running time of approximately 6 months. The APACHIE-01 study will contribute to the optimal design of a subsequent prospective trial. Full article

Background/Objectives: Breast cancer is the most common malignant neoplasm in women and the leading cause of cancer-related death. Approximately 50% of HER2-negative breast cancers exhibit low expression of this protein (HER2-low). Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate targeting the HER2 receptor which has shown benefit in patients with HER2-low metastatic breast cancer in the DESTINY-Breast04 study. However, few data are available on its efficacy in real-world practice. Methods: We conducted a retrospective multicenter national study (eight centers) including patients with advanced HER2-low breast cancer (immunohistochemistry 1+ or 2+/ in situ hybridization negative) who started T-DXd treatment between January 2022 and March 2024. Patients had received at least one previous line of treatment. The primary endpoint was real-world progression-free survival (rwPFS) in patients with metastatic HER2-low breast cancer treated with T-DXd. The secondary endpoints were real-world overall survival (OS) and objective response rate (ORR). Results: The study included 35 patients (34 female and 1 male patient), with a median age of 54 years at the start of T-DXd. All patients had an ECOG-PS 0–1, and 26 patients (74%) had hormone receptor (HR)-positive disease. The median number of prior lines of treatment was 4 [1–7], and 23 patients (65.8%) had metastases in three or more sites. With a median follow-up of 7.8 months, rwPFS was 6 months (95% CI, 2.3–9.7), and OS was 15 months (95% CI, 4.7–25.3). In HR-positive patients, the median rwPFS was 6 months (95% CI, 1.2–10.7), compared to 4 months (95% CI, 2.1–5.9) in HR-negative patients. The overall ORR was 52.9%. Adverse events of grade 3 or higher were neutropenia (2.9%) and fatigue (2.9%). Conclusions: This study provides real-world data on T-DXd in the treatment of advanced HER2-low breast cancer. It is noteworthy that the population was heavily pre-treated and had a higher proportion of HR-negative patients, which may explain the lower efficacy compared to the DESTINY-Breast04 study. Full article

This study examines a single-span beam crossing without longitudinal deformation compensators during diesel fuel pumping. In addition to static forces, namely, the weight of the pipeline and the transported product, the analysis considers vertical components of inertial forces acting on the oil product and the pipeline itself. These forces are directed perpendicularly to the abscissa axis connecting the endpoints of the crossing. The inertial effects cause significant vertical oscillations of the pipeline, which have not been sufficiently addressed in previous research. This work aims to study these oscillations to determine the displacements of points along the pipeline axis, the magnitudes of the inertial forces, and the resulting bending moments at the crossing. A classical Fourier series method is applied to solve the formulated boundary value problem. The results show that oscillations occur in the vertical plane, are symmetrical relative to the center of the span, and are undamped. The maximum vertical displacement reaches approximately 57 mm at the midpoint of the crossing, and the oscillation period is around 0.415 s. Inertial force distribution and bending moments are also symmetric about the center. A detailed analysis with small time steps confirmed that the oscillations are strictly periodic, exhibiting equal displacements in the upward and downward directions. The results highlight that fatigue loads arise during the operation of such crossings, which is important for assessing the strength and stability of oil pipeline structures under real operating conditions. Full article

Background and Objectives: ROS1 rearrangement is a rare but targetable alteration in non-small-cell lung cancer (NSCLC), occurring in 1–2% of cases. Crizotinib, a tyrosine kinase inhibitor, has demonstrated efficacy in clinical trials, but real-world data remain limited. This study evaluates the safety and efficacy of crizotinib in ROS1-rearranged NSCLC patients in a real-world setting. Materials and Methods: This multicenter, retrospective research included 43 individuals with advanced/metastatic NSCLC and confirmed ROS1 rearrangements. Patients were treated with crizotinib in first- or second-line settings. Efficacy endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Safety was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: The median follow-up was 45.8 months. The ORR for first-line crizotinib was 72.1%, with a DCR of 79%. The median PFS was 20.9 months (95% CI: 6.02–35.69), and the median OS was 52.7 months (95% CI: 13.08–92.31). ECOG performance status was a significant prognostic factor for ORR (p = 0.02). The most common adverse events were fatigue (16.2%), elevated transaminases (13.9%), and vision disorders (11.6%). All reported adverse events were grade 1 or 2, with no grade ≥ 3 events observed. Conclusions:Crizotinib demonstrated significant efficacy and a favorable safety profile in real-world individuals with ROS1-rearranged NSCLC. These findings align with pivotal trials, underscoring crizotinib’s role as a standard treatment for this molecular subset. Further prospective studies are warranted to explore intracranial efficacy and long-term outcomes. Full article

Background/Objectives: Traditional Chinese medicine (TCM) has a long history and is known for its anti-inflammatory, antiviral, and immunoregulatory qualities. It has been extensively studied during the COVID-19 pandemic. Therefore, to evaluate the relationship between TCM and the treatment of COVID-19, we conducted a meta-analysis. Methods: Our meta-analysis included 22 randomized clinical trials, which investigated the analyzed endpoints: time to recovery from fever, severity of dyspnea or breathlessness according on different scales, time to recovery for coughing, including dry and wet coughing, time to recovery for fatigue, changes in respiratory rate, length of hospitalization, hospital discharging rate, number of intensive care unit (ICU) admissions, number of cases requiring any supplemental oxygenation, number of deaths among COVID-19 patients, conversion rate of SARS-CoV-2 tests on a particular day, and time to viral assay conversion. The relative risk (RR) with 95% confidence intervals (CIs) and the mean difference or standardized mean difference with 95% CIs were calculated to compare the effect. A random effects model was used to calculate effect sizes. Results: We indicated a positive effect of TCM on different COVID-19 symptoms. TCM influences hospitalization duration, ICU admission, mortality, and time to viral assay conversion among COVID-19 patients. Moreover, TCM positively affects SARS-CoV-2 test conversion rates on particular days (RR = 1.21; 95% CI [1.10; 1.32]; p < 0.0001; I² = 84%). Conclusions: TCM may potentially support the standard treatment of COVID-19. Nevertheless, the necessity for further randomized trials with a greater number of participants and in a wider range of countries remains apparent. Full article

Background and Objectives: Long-term sequalae of viral diseases, especially after infections with SARS-CoV-2 (COVID-19), can induce multi-organ involvement, as around 65 million people worldwide report persistent symptoms that go far beyond the acute course. Studies indicate that early virus variants pose a higher risk of developing post-COVID-19 conditions. The primary aim of this study was to investigate the possible long-term effects based on the hospitalization rates and associated clinical events in patients infected with SARS-CoV-2 over an observational period of three years after the initial infection. Secondarily, an investigation of health-related quality of life and functional status was performed. Methods and Materials: The study presented was designed as a prospective, controlled cohort study to follow up on COVID-19 cases in the district of Konstanz, Germany (FSC19-KN). The positive group included subjects who had a primary infection with SARS-CoV-2 between March and December 2020. The control group included subjects who did not have a SARS-CoV-2 infection, as evidenced by a negative antibody test. As the primary endpoint, hospitalization rates and respective related admission diagnosis during the observational period of three years from January 2021 until July 2024 were analyzed. The health-related quality of life and functional outcomes were measured by the SF-36 questionnaire and Post-COVID-19 Functional Status (PCFS) as the secondary endpoint. Results: During the three years of observation after inclusion in the study, the hospitalization rate did not differ significantly between the two groups of initially infected and non-infected subjects (cumulative events, verum group 57 to control group 45, OR 1.24, CI 0.83; 1.85, p = 0.30). However, the health-related quality of life, measured by SF-36 sub scores of the SARS-CoV-2-positive subjects, achieved significantly lower results, except for the dimension ‘energy and fatigue’, in which subjects of the verum group still achieved significantly lower scores. Conclusions: Mild COVID-19 cases have no significant impact on hospitalization rates during an observational period of three years after initial infection. Yet, SARS-CoV-2-positive subjects reported a reduced health-related quality of life and functional outcomes. Ultimately, only the sub score quality ‘energy and fatigue’ still registered significant differences between both cohorts at the end of the three-year observational period. Full article

Since fan blades are exposed to fatigue, and in some cases harsh loading conditions, they may exhibit fracture failures due to crack propagation, resulting in significant losses. Previous studies of crack propagation in blades are mainly confined to either simplified blade geometry or loads, resulting in a significant discrepancy between the simulated crack propagation and the real blade propagation behavior, while it is lacking for challenging shapes and loads. A co-simulation approach of FRANC3D and ABAQUS was developed to study the crack propagation of an axial-flow fan blade subjected to centrifugal, aerodynamic, and combined loads. The projected approach is validated with results obtained from analytical calculations and experiments. Meanwhile, making use of benchmarks, the Stress Intensity Factor (SIF) and the prediction of mixed-mode crack growth path are validated. Considering various loads, the crack propagation path response for the fan blade is computed for different growth steps. The results pinpoint that the crack propagation length of the crack tip center is maximum under centrifugal loading. However, the aerodynamic load led to a maximum propagation length of the crack tip endpoints. In addition, the combined force of centrifugal and aerodynamic loads limits the crack from growing. Full article

Background: Neuroendocrine carcinomas (NECs) are treated with a frontline platinum–etoposide combination with no standard second-line therapies. We explored a novel combination of nanoliposomal irinotecan (Nal-IRI), 5-fluorouracil (5-FU), and leucovorin (LV) in advanced refractory NECs and investigated the impact of UGT1A1*28 polymorphism on treatment outcomes and toxicity. Methods: We conducted an open-label, single-arm, multi-center Phase 2 trial in advanced NEC patients of gastroenteropancreatic (GEP) or unknown origin with progression or intolerance to first-line therapy. Eligible patients received nal-IRI 70 mg/m² and leucovorin 400 mg/m², followed by 5-FU 2400 mg/m² biweekly till disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Next-generation sequencing (NGS) was performed on blood/tissue samples at baseline and during treatment. Results: Eleven patients were enrolled, with nine evaluable for the primary endpoint. Seven were male, the median age was 66.7 years, and the median Ki-67 was 90%. We observed partial response in one patient, stable disease in six patients, and progressive disease in two patients. The median OS was 9.4 months (95% CI 2.9–29.3), and the median PFS was 4.4 months (95% CI 1.7–6.7). The most common adverse events were diarrhea (45%), nausea (45%), vomiting (45%), and fatigue (45%). The most common genetic mutations on NGS were TP53 (88.9%), CHEK2 (88.9%), and APC (33.3%). Patients with CHEK2 and APC mutation had longer PFS (p = 0.005 and p = 0.013, respectively). UGT1A1*28 polymorphism was not associated with OS, PFS, or toxicity. Conclusion: Nal-IRI with 5-FU/LV is a safe and effective treatment for refractory high-grade NECs of GEP or unknown origin. Future studies should explore novel combinations with Nal-IRI in high-grade NECs both in frontline and refractory settings. Full article

This is the first article that investigates whether the patient-reported outcome measures (PROMs) used in clinical trials effectively capture the specific side-effects of radiotherapy and proton beam therapy (PBT) and provides context for researchers selecting PROMs for clinical trials. PROMs from radiotherapy trials were identified from previous research and assessed against the United Kingdom Royal College of Radiologists’ guidelines for tumour-site-specific side-effects. The analysis revealed that none of the 51 identified PROMs captured the full range of side-effects, with only 25 addressing fatigue and 6 addressing radiation-induced skin reactions. Three PROMs failed to identify any common side-effects, and eight identified only one. Overall, 88% of PROMs lacked specificity to radiotherapy and PBT, posing a risk of missing significant differences between treatment techniques. This study emphasises the need for more targeted PROMs in future trials. Until new or improved PROMs are available, great thought and caution should be taken when selecting PROMs for trial endpoints. Full article

Approximately 31% of patients previously infected with SARS-CoV-2 are living with symptoms of long COVID in the United States. Long COVID significantly reduces quality of life and increases morbidity and disability; however, treatment options are limited. Enhanced External Counterpulsation (EECP) is an FDA-approved, non-invasive treatment for the management of cardiovascular symptoms with a mechanism of action which stimulates pathways that induce endothelial homeostasis, improving microvascular function, inflammation, and immune regulation, thereby potentially targeting the underlying etiology of long COVID. We recently reported that EECP improved symptoms in 231 patients with long COVID. Previous studies assessing the effects of EECP for long COVID have lacked a control group. As such, this analysis is the first comparing outcomes in patients with long COVID undergoing EECP (n = 33) to a non-treated group (control, n = 33). The patients were matched for baseline characteristics, and all patients completed patient-reported outcome assessments, including PROMIS Fatigue, the Duke Activity Status Index (DASI), and the Rose Dyspnea Scale (RDS), two times within a specified time interval. When comparing the average change from baseline in both groups, the EECP-treated patients’ improvement was significantly greater than the improvement in the control group across all measured endpoints, including PROMIS Fatigue (−15.0 ± 8.9 vs. −2.8 ± 5.9, p < 0.001) and DASI (+17.8 (11.8, 26.8) vs. +1.8 (−3.5, 5.5), p < 0.001), and there was an improvement of ≥1 in the RDS class (75.8% vs. 33.3%, p < 0.001). This study’s limitations include the small sample size and lack of information regarding concurrent treatments or interventions in the non-treated group; however, these preliminary data support EECP as a potential low-risk treatment option for patients with long COVID. Full article

Background. Due to its antioxidant, anti-inflammatory, anti-apoptosis, and anti-fatigue properties, molecular hydrogen (H₂) is potentially a novel therapeutic nutrient for patients with coronavirus acute disease 2019 (COVID-19). We determined the efficacy and safety profile of hydrogen-rich water (HRW) to reduce the risk of COVID-19 progression. Methods: We also conducted a phase 3, triple-blind, randomised, placebo-controlled trial to evaluate treatment with HRW initiated within 5 days after the onset of signs or symptoms in primary care patients with mild-to-moderate, laboratory-confirmed COVID-19. Participants were randomised to receive HRW or placebo twice daily for 21 days. The incidence of clinical worsening and adverse events were the primary endpoints. Results: A total of 675 participants were followed up to day 30. HRW was not superior to placebo in preventing clinical worsening at day 14: in H₂ group, 46.1% in the H₂ group, 43.5% in the placebo group, hazard ratio 1.09, 90% confidence interval [0.90–1.31]. One death was reported at day 30 in the H₂ group and two in the placebo group at day 30. Adverse events were reported in 91 (27%) and 89 (26.2%) participants, respectively. Conclusions: HRW taken twice daily from the onset of COVID-19 symptoms for 21 days did not reduce clinical worsening. Full article

Background: The one-person technique (OPT) for colonoscope insertion is recommended by professional societies and regarded as standard practice. However, the two-person technique (TPT) has shown several advantages over the OPT. The aim of this study was to evaluate the performance of the TPT compared to the OPT. Methods: In this prospective study, consecutive individuals presenting for outpatient colonoscopy were randomized to undergo colonoscopy by OPT or by TPT. The colonoscopies were performed by six endoscopists, two of whom were beginners, two with intermediate skills, and two who were experts. The primary endpoints were quality indicators for colonoscopy, including adenoma detection rate, cecal intubation rate, cecal insertion time, and total colonoscopy time. A secondary outcome was procedure tolerability, as assessed by both the patients and the endoscopists. Results: Two hundred and four subjects (117 males, mean age 54.3) were randomized to either one- (n = 102) or two-person (n = 102) colonoscopy. The adenoma detection rate was 30.4% in OPT group and 34.3% in TPT group. (p = 0.55). No significant differences between the two groups were found in terms of cecal intubation rate (98/102 vs. 98/102), insertion time (411 vs. 381 s), and total examination time (1426 vs. 1296 s). However, patients receiving the TPT had lower pain scores than patients receiving the OPT. Endoscopist fatigue measured with the FACIT-F was also significantly lower in the TPT group. Conclusion: The two-person colonoscopy method was not shown to be technically or clinically inferior. Rather, the TPT can improve patient tolerance and reduce endoscopist fatigue. Full article

Background: Acute cardiac injury (ACI) after COVID-19 has been linked with unfavorable clinical outcomes, but data on the clinical impact of elevated cardiac troponin on discharge during follow-up are scarce. Our objective is to elucidate the clinical outcome of patients with elevated troponin on discharge after surviving a COVID-19 hospitalization. Methods: We conducted an analysis in the prospective registry HOPE-2 (NCT04778020). Only patients discharged alive were selected for analysis, and all-cause death on follow-up was considered as the primary endpoint. As a secondary endpoint, we established any long-term COVID-19 symptoms. HOPE-2 stopped enrolling patients on 31 December 2021, with 9299 patients hospitalized with COVID-19, of which 1805 were deceased during the acute phase. Finally, 2382 patients alive on discharge underwent propensity score matching by relevant baseline variables in a 1:3 fashion, from 56 centers in 8 countries. Results: Patients with elevated troponin experienced significantly higher all-cause death during follow-up (log-rank = 27.23, p < 0.001), and had a higher chance of experiencing long-term COVID-19 cardiovascular symptoms. Specifically, fatigue and dyspnea (57.7% and 62.8%, with p-values of 0.009 and <0.001, respectively) are among the most common. Conclusions: After surviving the acute phase, patients with elevated troponin on discharge present increased mortality and long-term COVID-19 symptoms over time, which is clinically relevant in follow-up visits. Full article

Background: Electromagnetic transponders bronchoscopically implanted near the tumor can be used to monitor deep inspiration breath hold (DIBH) for thoracic radiation therapy (RT). The feasibility and safety of this approach require further study. Methods: We enrolled patients with primary lung cancer or lung metastases. Three transponders were implanted near the tumor, followed by simulation with DIBH, free breathing, and 4D-CT as backup. The initial gating window for treatment was ±5 mm; in a second cohort, the window was incrementally reduced to determine the smallest feasible gating window. The primary endpoint was feasibility, defined as completion of RT using transponder-guided DIBH. Patients were followed for assessment of transponder- and RT-related toxicity. Results: We enrolled 48 patients (35 with primary lung cancer and 13 with lung metastases). The median distance of transponders to tumor was 1.6 cm (IQR 0.6–2.8 cm). RT delivery ranged from 3 to 35 fractions. Transponder-guided DIBH was feasible in all but two patients (96% feasible), where it failed because the distance between the transponders and the antenna was >19 cm. Among the remaining 46 patients, 6 were treated prone to keep the transponders within 19 cm of the antenna, and 40 were treated supine. The smallest feasible gating window was identified as ±3 mm. Thirty-nine (85%) patients completed one year of follow-up. Toxicities at least possibly related to transponders or the implantation procedure were grade 2 in six patients (six incidences, cough and hemoptysis), grade 3 in three patients (five incidences, cough, dyspnea, pneumonia, and supraventricular tachycardia), and grade 4 pneumonia in one patient (occurring a few days after implantation but recovered fully and completed RT). Toxicities at least possibly related to RT were grade 2 in 18 patients (41 incidences, most commonly cough, fatigue, and pneumonitis) and grade 3 in four patients (seven incidences, most commonly pneumonia), and no patients had grade 4 or higher toxicity. Conclusions: Bronchoscopically implanted electromagnetic transponder–guided DIBH lung RT is feasible and safe, allowing for precise tumor targeting and reduced normal tissue exposure. Transponder–antenna distance was the most common challenge due to a limited antenna range, which could sometimes be circumvented by prone positioning. Full article

Reciprocating motion expands the lifetime of endodontic instruments during the preparation of severely curved root canals. This study aimed to investigate the time to fracture (TTF) and number of cycles to failure (NCF) of different reciprocating instruments (n = 20 in each group) at body temperature using a dynamic testing model (amplitude = 3 mm). Reciproc Blue (RPB), size 25/.08, WaveOne Gold (WOG) 25/.07, Procodile (Proc) 25/.06, R-Motion (RM_06) 25/.06 and R-Motion (RM_04) 30/.04 instruments were tested in their specific reciprocating motion in artificial matching root canals (size of the instrument ± 0.02 mm; angle of curvature 60°, radius 5.0 mm, and centre of curvature 5.0 mm from apical endpoint). The number of fractured instruments, TTF, NCF, the and lengths of the fractured instruments were recorded and statistically analysed using the Chi-Square or Kruskal–Wallis test. Both TTF (median 720, 643, 562, 406, 254 s) and the NCF (3600, 3215, 2810, 2032, 1482 cycles) decreased in the following order RM_06 > RPB > RM_04 > Proc > WOG with partially significant differences. During testing, only six RM_06 instruments fractured, whereas 16/20 (RPB), 18/20 (Proc), and 20/20 (RM_04, WOG) fractures were recorded (p < 0.05). Within the limitations of the present study, blue-coloured RPB and RM instruments exhibited a significantly superior cyclic fatigue resistance compared to SE-NiTi and Gold-wire instruments. Heat treatment, cross-sectional design and core mass significantly influenced the longevity of reciprocating instruments in cyclic dynamic testing. Full article