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  • 1
    Online Resource
    Online Resource
    Assessing the Performance of a Novel Stool-Based Microbiome Test That Predicts Response to First Line Immune Checkpoint Inhibitors in Multiple Cancer Types
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 13 ( 2023-06-21), p. 3268-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 13 ( 2023-06-21), p. 3268-
    Abstract: The intestinal microbiome is by now an undebatable key player in the clinical outcome of ICI therapies. However, no microbiome profiling method to aid therapy decision is yet validated. We conducted a multi-centric study in patients with stage III/IV melanoma, NSCLC, or RCC receiving ICI treatment. The stool microbiome profile of 63 patients was analyzed with BiomeOne®, a microbiome-based algorithm that anticipates whether a patient will achieve clinical benefit with ICIs prior to therapy initiation. Classification of patient samples as Rs and NRs was achieved with a sensitivity of 81% and a specificity of 50% in this validation cohort. An ICI-favorable response was characterized by an intestinal microbiome rich in bacteria such as Oscillospira sp., Clostridia UCG-014, Lachnospiraceae UCG-010 sp., Prevotella copri, and a decrease in Sutterella sp., Lactobacillales, and Streptococcus sp. Patients who developed immune-related adverse events (irAEs) had an overall increased microbial diversity and richness, and a stool microbiome depleted in Agathobacter. When compared with the programmed death-ligand 1 (PD-L1) expression test in the subcohort of NSCLC patients (n = 38), BiomeOne® exhibited a numerically higher sensitivity (78.6%) in identifying responders when compared with the PD-L1 test (67.9%). This study provides an evaluation of BiomeOne®, the first microbiome-based test for prediction of ICI response, to achieve market authorization. Validation with further indications and expansion to other microbiome-based interventions will be essential to bring microbiome-based diagnostics into standard clinical practice.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15133268
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 2
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    Multimodal Treatment of Malignant Pleural Mesothelioma: Real-World Experience with 112 Patients
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 9 ( 2022-04-30), p. 2245-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 9 ( 2022-04-30), p. 2245-
    Abstract: Malignant pleural mesothelioma (MPM) is a rare pleural cancer associated with asbestos exposure. According to current evidence, the combination of chemotherapy, surgery and radiotherapy improves patients’ survival. However, the optimal sequence and weighting of the respective treatment modalities is unclear. In anticipation of the upcoming results of the MARS-2 trial, we sought to determine the relative impact of the respective treatment modalities on complications and overall survival in our own consecutive institutional series of 112 patients. Fifty-seven patients (51%) underwent multimodality therapy with curative intent, while 55 patients (49%) were treated with palliative intent. The median overall survival (OS) of the entire cohort was 16.9 months (95% CI: 13.4–20.4) after diagnosis; 5-year survival was 29% for patients who underwent lung-preserving surgery. In univariate analysis, surgical treatment (p 〈 0.001), multimodality therapy (p 〈 0.001), epithelioid subtype (p 〈 0.001), early tumor stage (p = 0.02) and the absence of arterial hypertension (p = 0.034) were found to be prognostic factors for OS. In multivariate analysis, epithelioid subtype was associated with a survival benefit, whereas the occurrence of complications was associated with worse OS. Multimodality therapy including surgery significantly prolonged the OS of MPM patients compared with multimodal therapy without surgery.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14092245
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 3
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    Online Resource
    Later-Line Treatment with Lorlatinib in ALK- and ROS1-Rearrangement-Positive NSCLC: A Retrospective, Multicenter Analysis
    MDPI AG ; 2020
    In:  Pharmaceuticals Vol. 13, No. 11 ( 2020-11-07), p. 371-
    Details
    In: Pharmaceuticals, MDPI AG, Vol. 13, No. 11 ( 2020-11-07), p. 371-
    Abstract: In clinical practice, patients with anaplastic lymphoma kinase (ALK)-rearrangement–positive non–small-cell lung cancer commonly receive sequential treatment with ALK tyrosine kinase inhibitors. The third-generation agent lorlatinib has been shown to inhibit a wide range of ALK resistance mutations and thus offers potential benefit in later lines, although real-world data are lacking. This multicenter study retrospectively investigated later-line, real-world use of lorlatinib in patients with advanced ALK- or ROS1-positive lung cancer. Fifty-one patients registered in a compassionate use program in Austria, who received second- or later-line lorlatinib between January 2016 and May 2020, were included in this retrospective real-world data analysis. Median follow-up was 25.3 months. Median time of lorlatinib treatment was 4.4 months for ALK-positive and 12.2 months for ROS-positive patients. ALK-positive patients showed a response rate of 43.2%, while 85.7% percent of the ROS1-positive patients were considered responders. Median overall survival from lorlatinib initiation was 10.2 and 20.0 months for the ALK- and ROS1-positive groups, respectively. In the ALK-positive group, lorlatinib proved efficacy after both brigatinib and alectinib. Lorlatinib treatment was well tolerated. Later-line lorlatinib treatment can induce sustained responses in patients with advanced ALK- and ROS1-positive lung cancer.
    Type of Medium: Online Resource
    ISSN: 1424-8247
    URL: Article
    DOI: 10.3390/ph13110371
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2193542-7
    SSG: 15,3
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  • 4
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    Online Resource
    Soluble ST2 and All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease—A 10-Year Cohort Study
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 11, No. 1 ( 2021-12-23), p. 56-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 1 ( 2021-12-23), p. 56-
    Abstract: Chronic obstructive pulmonary disease (COPD) is an inflammatory condition with constantly increasing mortality rates. Interleukin (IL)-33 and its decoy receptor, soluble suppression of tumorigenicity 2 (sST2), play a central role in the inflammatory response during infection. sST2 was suggested as a factor in the pathogenesis of COPD and emerged as a predictor of mortality in other non-communicable diseases. The role of sST2 as a predictor of mortality remains unclear in COPD yet. In this cohort study, we measured circulating concentrations of IL-33 and sST2 in the serum of patients with stable COPD (n = 59), patients with acute exacerbation of COPD (n = 29) and smoking (n = 20) and non-smoking controls (n = 20), using commercially available ELISAs, and investigated the prognostic role of sST2 in stable COPD. sST2 levels were significantly higher in COPD patients and smokers compared with non-smoking controls. We identified systolic blood pressure, forced expiratory volume in 1 s (FEV1% predicted), neutrophil count, lactate dehydrogenase and pack-years index as independent predictors of sST2 levels. During a median follow-up time of 10.6 years, 28 patients (47.5%) died. sST2 was an independent predictor of all-cause mortality in patients with COPD with a hazard ratio of 2.9 (95% CI 1.1–8.4, p = 0.035) per one standard deviation after adjustment for age, sex, pack-years, FEV1% predicted and C-reactive protein (CRP). sST2 concentrations are associated with severity of disease and long-term outcome in patients with COPD.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11010056
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 5
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    Online Resource
    Modern Bronchoscopic Treatment Options for Patients with Chronic Bronchitis
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 5 ( 2023-02-26), p. 1854-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 5 ( 2023-02-26), p. 1854-
    Abstract: Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of death worldwide and has a large impact on a patient’s quality of life due to its wide range of symptoms and comorbidities. There are known to be different phenotypes in COPD with various extents on the burden of the disease and its prognosis. Chronic bronchitis with persistent cough and mucus production is regarded as one of the main symptoms of COPD with tremendous effects on subjectively reported symptom burden and frequency of exacerbations. Exacerbations in turn are known to have an impact on disease progression and increase health care costs. Modern bronchoscopic treatment options are currently under investigation targeting the problem of chronic bronchitis and frequent exacerbations. This review summarizes the existing literature about these modern interventional treatment options and provides perspectives on upcoming studies.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12051854
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
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  • 6
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    Characteristics and Treatment Outcomes in Advanced-Stage Non-Small Cell Lung Cancer Patients with a KRAS G12C Mutation: A Real-World Study
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 14 ( 2022-07-15), p. 4098-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 14 ( 2022-07-15), p. 4098-
    Abstract: About 15% of patients with non-small cell lung cancer (NSCLC) harbor the Kirsten rat sarcoma homolog G12C mutation (KRASG12C). Selective KRASG12C inhibitors offer new treatment opportunities, but little is known about the prevalence, characteristics, and outcomes of standard-of-care treatment (SOC) in this population. We retrospectively assessed the clinicopathological features of patients with KRASG12C-mutated advanced NSCLC and responses to SOC at two high-volume centers in Austria. Out of 2495 NSCLC patients tested, we identified 174 patients with advanced-stage disease carrying a KRASG12C mutation. Most patients were ≥65 years old (55%), heavy smokers (55%), and presented with comorbidities. The most frequent co-alteration was TP53 (18%). PD-L1 expression was high (TPS ≥ 50%) in 31%, very high (TPS ≥ 90%) in 11%, and negative in 31% of patients. A total of 138 patients (79%) received oncologic systemic treatment. The most common first-line therapy (1 L) was anti-PD-1/PD-L1 plus platinum-based chemotherapy. Median overall survival measured from 1 L treatment was 15.3 months (95% CI, 8.6–21.9), 9.4 (95% CI, 5.3–13.5) from 2 L treatment, and 8.4 (95% CI, 1.7–15.1) from 3 L treatment. The time-to-next-treatment was 8.4 (95% CI, 5.2–11.6) from 1 L and 6.1 (95% CI, 2.7–9.7) months from 2 L to 3 L. These poor outcomes underscore the need for the implementation of new treatment options and for specific molecular testing.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11144098
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 7
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    Effectiveness of Outpatient Pulmonary Rehabilitation in Patients with Surgically Resected Lung Cancer: A Retrospective Real-World Analysis
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 14 ( 2022-07-18), p. 3479-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 14 ( 2022-07-18), p. 3479-
    Abstract: Patients with lung cancer frequently suffer from physical deconditioning, low exercise capacity, and reduced quality of life. There is little evidence on the effects of a structured outpatient pulmonary rehabilitation program (OPR) on exercise capacity and symptom load in these patients. We performed a retrospective, single-center analysis of surgically resected lung cancer patients, who underwent a multiprofessional 6-week OPR. The primary endpoint was a change in the six-minute walk test distance (6 MWT). Secondary endpoints included changes in maximal workload and constant work-rate test results during cycle-ergometry, upper and lower extremity strength, and inspiratory muscle strength. The COPD Assessment Test (CAT) was used to assess symptom burden. Fifty-seven patients were included. Of those, fifty-two (91.2%) completed the full 6 weeks of OPR. The mean age was 56.4 (SD 9.2) years, and 58% were female. At completion of OPR, there was a statistically significant mean of a 50 m (95% CI, 29.6–70.7; p 〈 0.001) increase in 6 MWT. Significant improvements were also seen in all other exercise and strength tests (p 〈 0.001), accompanied by a significant reduction in the CAT score (mean difference −3.1, p = 0.001). No adverse effects were reported. OPR for surgically resected lung cancer patients was safe and effective and showed high adherence in the current study.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14143479
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 8
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    Online Resource
    Therapeutic Success in Swiss COPD Patients Receiving Dual Bronchodilation Therapy as COPD Maintenance Treatment
    MDPI AG ; 2022
    In:  Clinics and Practice Vol. 12, No. 1 ( 2022-01-07), p. 46-56
    Details
    In: Clinics and Practice, MDPI AG, Vol. 12, No. 1 ( 2022-01-07), p. 46-56
    Abstract: Health-related quality of life (HRQoL) in patients with moderate to severe chronic obstructive pulmonary disease (COPD) is often reduced by high symptom burden and frequent exacerbations. So far, data on therapeutic success in Swiss COPD patients receiving dual bronchodilation therapy as COPD maintenance treatment are limited. Data from a recently published, non-interventional study on clinical benefit after the start of combined tiotropium–olodaterol treatment were analyzed focusing on Swiss patients compared to the overall cohort including patients from various European countries. Demographic data on the changes in Clinical COPD Questionnaire (CCQ) for the assessment of HRQoL in correlation to symptoms and the number of exacerbations, as well as physician’s global assessment (PGE), were evaluated 6 weeks after treatment start. In Switzerland (n = 61), significantly more patients had comorbidities and exacerbations but showed less symptoms compared to the overall cohort (n = 4639). HRQoL improved in both cohorts, with a negative correlation to symptom burden and number of exacerbations in the overall cohort. PGE scores improved after 6 weeks with a better general condition at baseline in Swiss patients (PGE score 4/5: 68.9% [Swiss cohort] vs. 49.0% [overall cohort] . Despite significant differences regarding the presence of symptoms and exacerbations, therapeutic success was similar in both patient groups. Highly symptomatic patients benefited mostly from tiotropium–olodaterol treatment.
    Type of Medium: Online Resource
    ISSN: 2039-7283
    URL: Article
    DOI: 10.3390/clinpract12010006
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2605724-4
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  • 9
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    Online Resource
    “Nitrogen Wash-Out” in Non-Hypoxaemic Patients with Spontaneous Pneumothorax: A Narrative Review
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 13 ( 2023-06-27), p. 4300-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 13 ( 2023-06-27), p. 4300-
    Abstract: Following current guidelines, spontaneous pneumothorax should be primarily managed with minimal invasive strategies. In real-world clinical practice, oxygen supplementation regardless of the presence or absence of hypoxemia is frequently applied in patients with a pneumothorax, with the intention to enhance the resorption rate of air from the pleural cavity (“nitrogen wash-out theory”). This review provides an overview of the scientific origin of this practice in animal models, and its clinical use in adult and paediatric patients. Clinical studies from PubMed, Embase and Cochrane library were reviewed by the authors using the keywords, “oxygen AND pneumothorax”, “nitrogen washout AND pneumothorax” and “nitrogen AND pneumothorax”, and recommendations from current guidelines were also reviewed by the authors. A selected total of nine clinical studies and three guidelines were included. Though in animal models there appears to be a therapeutic effect of oxygen therapy for the treatment of pneumothorax, clinical data in patient populations mainly stem from retrospective studies, mostly with a small sample size and inadequate study design. We recommend conducting prospective clinical studies with adequate methodology to address the question of whether or not oxygen therapy should be used to treat pneumothorax, regardless of the presence or absence of hypoxemia.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12134300
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 10
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    Online Resource
    Influence of Achalasia on the Spirometry Flow–Volume Curve and Peak Expiratory Flow
    MDPI AG ; 2024
    In:  Diagnostics Vol. 14, No. 9 ( 2024-04-29), p. 933-
    Details
    In: Diagnostics, MDPI AG, Vol. 14, No. 9 ( 2024-04-29), p. 933-
    Abstract: Background: Achalasia is an esophageal motor disorder characterized by aperistalsis and the failure of the relaxation of the lower esophageal sphincter. We want to find out whether external compression or recurrent micro-aspiration of undigested food has a functional effect on the airway. Methods: The aim of this research was to analyze the influence of achalasia on the peak expiratory flow and flow–volume curve. All of the 110 patients performed spirometry. Results: The mean diameter of the esophagus was 5.4 ± 2.1 cm, and nine of the patients had mega-esophagus. Seven patients had a plateau in the inspiratory part of the flow–volume curve, which coincides with the patients who had mega-esophagus. The rest of the patients had a plateau in the expiration part of the curve. The existence of a plateau in the diameter of the esophagus of more than 5 cm was significant (p 0.003). Statistical significance between the existence of a plateau and a lowered PEF (PEF 〈 80) has been proven (p 0.001). Also, a statistical significance between the subtype and diameter of more than 4 cm has been proved. There was no significant improvement in the PEF values after operation. In total, 20.9% of patients had a spirometry abnormality finding. The frequency of the improvement in the spirometry values after surgery did not differ significantly by achalasia subtype. The improvement in FEV1 was statistically significant compared to the FVC values. Conclusions: Awareness of the influence of achalasia on the pulmonary parameters is important because low values of PEF with a plateau on the spirometry loop can lead to misdiagnosis. The recognition of various patterns of the spirometry loop may help in identifying airway obstruction caused by another non-pulmonary disease such as achalasia.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics14090933
    Language: English
    Publisher: MDPI AG
    Publication Date: 2024
    detail.hit.zdb_id: 2662336-5
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