Adhesion, metastasis, and inhibition of cancer cells: a comprehensive review.

This comprehensive review delves into cancer's complexity, focusing on adhesion, metastasis, and inhibition. It explores the pivotal role of these factors in disease progression and therapeutic strategies. This review covers cancer cell migration, invasion, and colonization of distant organs, emphasizing the significance of cell adhesion and the intricate metastasis process. Inhibition approaches targeting adhesion molecules, such as integrins and cadherins, are discussed. Overall, this review contributes significantly to advancing cancer research and developing targeted therapies, holding promise for improving patient outcomes worldwide. Exploring different inhibition strategies revealed promising therapeutic targets to alleviate adhesion and metastasis of cancer cells. The effectiveness of integrin-blocking antibodies, small molecule inhibitors targeting Focal adhesion kinase (FAK) and the Transforming Growth Factor ß (TGF-ß) pathway, and combination therapies underscores their potential to disrupt focal adhesions and control epithelial-mesenchymal transition processes. The identification of as FAK, Src, ß-catenin and SMAD4 offers valuable starting points for further research and the development of targeted therapies. The complex interrelationships between adhesion and metastatic signaling networks will be relevant to the development of new treatment approaches.

Deventilation Syndrome in COPD Patients Receiving Long-Term Home Noninvasive Ventilation: A Systematic Scoping Review.

The treatment of patients with COPD and chronic hypercapnic respiratory failure using noninvasive ventilation (NIV) is well established. A "deventilation syndrome" (DVS) has been described as acute dyspnea after cessation of NIV therapy. A systematic scoping review reporting according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) searching Embase was conducted in September 2021. A final manual search followed in February 2023. Literature synthesis was blinded using Rayyan by three different reviewers. A total of 2,009 studies were screened. Five studies met the eligibility criteria. Four articles presented original data. Three articles examined potential treatment options. Three studies were prospective; none were randomized. A total of 122 patients were included. DVS was defined differently in all studies. Seventy-four patients were identified to suffer from DVS (48 controls). Patients were evaluated by blood gas analysis, transcutaneous TcCO2 measurement, spirometry, whole-body plethysmography, respiratory muscle assessments, diaphragmatic electromyography, ultrasound, 6-min walk test, polysomnography, and questionnaires. Treatment approaches studied were minimization of "patient-ventilator asynchrony" (PVA) and use of pursed- lip breathing ventilation. Pathophysiological mechanisms discussed were PVA, high inspiratory positive airway pressure, hyperinflation, respiratory muscle impairment, and increased respiratory rates. Compared with controls, patients with DVS appeared to suffer from more severe airway obstruction, hyperinflation, and PaCO2 retention; worse exercise test scores; and poorer quality of life. The available evidence does not allow for definite conclusions about pathophysiological mechanisms, ethology, or therapeutic options. Future studies should focus on a consistent definition and possible pathomechanisms.

Impact of the COVID-19 pandemic on home mechanical ventilation in Germany: A descriptive observational study.

INTRODUCTION: Over the last decade, the number of patients receiving home mechanical ventilation (HMV) has increased significantly, which has led to a limited availability of specialist centres, not least due to the scarcity of healthcare professionals. This situation was exacerbated by the COVID-19 pandemic. It is therefore assumed that the repurposing of resources has led to an aggravated change in the healthcare structure in HMV. METHODS: This descriptive observational study analysed the Operation and Procedure Classification Codes for patients receiving HMV from 2008 to 2022. The data was provided by the Federal Statistical Office of Germany. Data were additionally analysed with respect to geographical distribution and ventilation status. RESULTS: 737,770 data sets were analysed (mean age 2020 66.5 years). There was a steady increase in HMV initiations (+6%) and controls (+9%) per year before the pandemic (2008-2019). Patient admissions during the pandemic revealed a 28% decrease, with the largest decrease in invasive ventilation (IV) follow-up visits (2019: 3,053; 2020: 2,199; -39%), while the number of IV initiations remained stable. There was a 19% decrease in the number of non-invasive ventilation initiations in 2020 (16,919 vs. 14,227) and a 32% decrease regarding follow-ups (45,812 vs. 34,813) in comparison to 2019. CONCLUSION: The pandemic has led to a significant decline of inpatient admissions for patients receiving HMV. This decline was most pronounced in the first year of the pandemic. Control visits in particular did not reach the pre-pandemic level. This is an indication of the ongoing change in the healthcare landscape as a result of the pandemic.

FDG-PET-CT as an early detection method for tuberculosis: a systematic review and meta-analysis.

Tuberculosis (TB) causes major public health problems worldwide. Fighting TB requires sustained efforts in health prevention, diagnosis and treatment. Previous literature has shown that conventional diagnostic methods like X-ray and sputum microscopy often miss early or extrapulmonary TB due to their limited sensitivity. Blood tests, while useful, lack the anatomical detail needed for precise localization of TB lesions. A possible step forward in the fight against TB could be the use of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and Computed Tomography (CT). This meta-analysis discusses the current literature, including the methods, results and implications of using FDG-PET-CT in the early diagnosis of TB. Analysis of the studies showed that the sensitivity of FDG-PET-CT as a potential method for early detection of TB was 82.6%.

[Pulmonary involvement in idiopathic inflammatory myopathies]. / Pulmonale Beteiligung bei idiopathischen inflammatorischen Myopathien.

Idiopathic inflammatory myopathies are rare systemic diseases with different types of pulmonary manifestations depending on the underlying aetiology; here, interstitial lung diseases (ILD) are the most frequently found patterns depending on the underlying disorder. There is a lack of sufficient prospective studies on this heterogeneous group of patients, particularly in case of ILD being involved. The diagnosis is based upon guideline recommendations for ILD and requires a multidisciplinary discussion within a team with specific expertise in this field. Myositis specific antibodies and myositis associated antibodies form an essential part of the diagnostic tools and may also be associated with a certain phenotype or disease progression. Anti-t-RNA-synthetase antibodies (Anti-ARS) and anti-melanoma differentiation-associated gene 5 antibodies (MDA5) play an important clinical role for treatment the estimation of response and prognosis. The most common ILD patterns are nonspecific interstitial pneumonia (NSIP) and organising pneumonia (OP) or a mixed pattern of both. Treatment is based on systemic steroids and early initiation of other immunosuppressant drugs. Evidence for this is, however, sparse, since most of the studies having investigated treatment modalities are of retrospective nature, even though some new prospective data may be useful for the establishment of treatment pathways in the future.

[Long-term health-related quality of life of patients after prolonged weaning depending on weaning status]. / Lebensqualität im Langzeitverlauf nach prolongiertem Weaning in Abhängigkeit vom Weaning-Status.

INTRODUCTION: Long-term outcome in patients with prolonged weaning is known to be impaired, particularly against the background of their weaning status; however, data on their health-related quality of life (HRQL) are sparse. METHODS: HRQL was measured in patients with prolonged weaning using the Severe Respiratory Insufficiency Questionnaire (SRI). RESULTS: Overall, 39 out of 83 patients with prolonged weaning filled in the SRI questionnaire. The median interval between discharge from hospital and HRQL assessment was 3.5 years (IQR 2.4-4.5 years). In the total group, the median SRI summary score was 56.4 (IQR 38.8-73.5). Patients with unsuccessful weaning and subsequent invasive home mechanical ventilation (N=15) had worse HRQL as estimated from the SRI summary score when compared to those with successful weaning both without (n=13) and with subsequent long-term non-invasive ventilation (NIV) (n=11); Kruskal-Wallis-Test: H (2, n=39) = 7,875446; P=0.0195. Statistically significant differences indicating worse HRQL in patients with invasive home mechanical ventilation were particularly evident in the following SRI subscales: Social relationships (P=0.0325), Anxiety (P=0.0096), and Psychological well-being (P=0.0079). CONCLUSIONS: HRQL is substantially impaired in patients with unsuccessful prolonged weaning and subsequent invasive home mechanical ventilation compared to those with successful prolonged weaning. Further studies incorporating higher case numbers are needed to assess other conditions potentially affecting HRQL in patients with prolonged weaning.

[Diagnosis and Treatment of Hypersensitivity Pneumonitis - S2k Guideline of the German Respiratory Society and the German Society for Allergology and Clinical Immunology]. / Diagnostik und Therapie der exogen-allergischen Alveolitis.

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) in sensitized individuals caused by a large variety of inhaled antigens. The clinical form of acute HP is often misdiagnosed, while the chronic form, especially the chronic fibrotic HP, is difficult to differentiate from other fibrotic ILDs. The present guideline for the diagnosis and treatment of HP replaces the former German recommendations for the diagnosis of HP from 2007 and is amended explicitly by the issue of the chronic fibrotic form, as well as by treatment recommendations for the first time. The evidence was discussed by a multidisciplinary committee of experts. Then, recommendations were formulated for twelve questions on important issues of diagnosis and treatment strategies. Recently published national and international guidelines for ILDs and HP were considered. Detailed background information on HP is useful for a deeper insight into HP and the handling of the guideline.

[Neuralgic amyotrophy: a common cause of unilateral and bilateral diaphragmatic pareses]. / Die neuralgische Amyotrophie: eine häufige Ursache uni- oder bilateraler Zwerchfellparesen.

There are several causes for unilateral or bilateral diaphragmatic paresis. The most common cause is an (intraoperative) injury to the phrenic nerve.However, in up to 20% of cases, no explanation can be found despite extensive workup. Neuralgic amyotrophy (NA, also known as Parsonage-Turner syndrome) is a common underdiagnosed multifocal autoimmune-inflammatory disease that predominantly affects proximal nerve segments of the upper extremities. Classic symptoms include acute onset of severe pain in the shoulder girdle with delayed onset of paresis of the shoulder and arm muscles. In at least 7% of cases, the phrenic nerve is also affected. Based on the annual incidence of NA of 1:1000, the entity as a cause of diaphragmatic dysfunction is probably not as uncommon as previously thought. However, clinical experience shows that this diagnosis is often not considered, and diaphragmatic paresis gets wrongly classified as idiopathic.This is particularly disastrous because in the early stage of NA, medical therapy with corticosteroids is mostly not considered and the possibility that surgical repair of the diaphragm may be performed prematurely, given that the condition may resolve spontaneously many months after symptom onset.The aim of the present article is to raise awareness of the entity of NA as a cause of diaphragmatic paresis and to establish a standardized approach to diagnosis and treatment.

[SARS-CoV-2-Infection and Interstitial Lung Disease: Position paper of the German Respiratory Society]. / SARS-CoV-2-Infektion und interstitielle Lungenerkrankungen ­ Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin.

The SARS-CoV-2 pandemic had a tremendous impact on diagnosis and treatment of interstitial lung diseases (ILD). Especially in the early phase of the pandemic, when the delta variant was prevailling, a huge number of viral pneumonias were observed, which worsened pre-existing, triggered de novo occurence or discovery of previously subclincal interstitial lung diseases. The effect of SARS-CoV-2 infection - without or with accompanying viral pneumonia - on the further development of pre-existing ILD as well of new pulmonary inflitrates and consolidiations is difficult to predict and poses a daily challenge to interdisciplinary ILD boards. This position paper of the German Respiratory Society (DGP e.V.) provides answers to the most pressing questions based on current knowledge.

Evolution of Web-Based Training Videos Provided by the German Respiratory League for the Correct Inhalation Technique.

BACKGROUND/OBJECTIVE: To assess whether and how the use of scientifically established Web-based training videos for teaching correct inhalation technique in patients with chronic airway diseases has become accepted among the wider population. METHODS: The viewing trends of 141 freely available YouTube videos (full playing time, 01:31-04:37 min:s) provided by the German Respiratory League, covering a broad range of internationally prescribed devices, were analyzed over a 10-year period. Specific emphasis was placed both on German and international videos. RESULTS: The total number of views was 3,350,678. Non-German videos (English, Russian, Turkish, Greek, Arabic, Farsi, and Slovakian) accounted for 23.2% of the views. The number of views steadily increased between 2011 and 2020 with a mean annual increase of 54.0% (range 24.5/119.9%) compared to the respective previous year. By 2020, the incidence of views per 100,000 German inhabitants was 725 for German videos only and 1,030 for all videos. In terms of the annual trend, there were two peak viewing periods, namely in spring and late fall, while the lowest amount of views occurred in summer. CONCLUSION: This study highlights the rising impact of Web-based training videos used for teaching the correct use of inhalation devices, with a steady increase in the number of annual views and a clear seasonal peaking of views in spring and late fall.

Plasma interferon-γ-inducible protein 10 (IP-10) levels correlate with disease severity and paradoxical reactions in extrapulmonary tuberculosis.

BACKGROUND: With 1.5 million deaths worldwide in 2018, tuberculosis (TB) remains a major global public health problem. While pulmonary TB (PTB) is the most common manifestation, the proportion of extrapulmonary TB (EPTB) is increasing in low-burden countries. EPTB is a heterogeneous disease entity posing diagnostic and management challenges due to the lack of reliable biomarkers. In this study, we prospectively evaluated clinical data and treatment response which were correlated with different biomarkers. METHODS: The study was conducted at the University Hospital of Cologne. 20 patients with EPTB were enrolled. We analyzed plasma interferon-γ-inducible protein 10 (IP-10) levels in plasma by ELISA for up to 12 months of treatment. In addition, the QuantiFERON®-TB Gold Plus (QFT® Plus) test was performed during the course of treatment. Clinical data were assessed prospectively and correlated with QFT® Plus and IP-10 levels. RESULTS: Plasma IP-10 levels were found to be significantly increased (p < 0.001) in patients with extensive disease compared to patients with limited disease (cervical lymph node TB) or healthy controls. In patients with clinically confirmed paradoxical reaction (PR), a further increase of IP-10 was noted. IFN-γ measured by the QFT® Plus test did not decrease significantly during the course of treatment. Of note, in four EPTB patients (20%) without radiographic pulmonary involvement, sputum culture was positive for Mycobacterium tuberculosis. CONCLUSION: Our data demonstrate that IP-10 may be a valuable biomarker for estimation of disease severity in EPTB and monitoring of the disease course in extensive forms. However, IP-10 may be less suitable for diagnosis and monitoring of EPTB patients with limited disease. The QFT® Plus test does not appear to be a suitable marker for therapy monitoring. Sputum should be examined in EPTB patients even in case of normal diagnostic imaging of the chest.

Structure Elucidation of the Main Tetrahydroxyxanthones of Hypericum Seeds and Investigations into the Testa Structure.

Seeds from Hypericum species have recently been identified as an interesting source of xanthone derivatives. Extraction of seeds from H. perforatum with MeOH and subsequent concentration via polyamide adsorption yielded a fraction enriched in tetrahydroxyxanthones (THX), which were further semipurified by silica gel chromatography. Based on tentative structure assignment of the two main THX X1 and X2 by NMR a total synthesis was performed for both compounds (THX 1 and 2, respectively), starting with an Ullmann ether synthesis. The synthesized 1 and 2 were characterized via 1D- and 2D-NMR methods as well as by LC/HR-MS analysis and proven to be 1,4,6,7-THX (1) and 1,2,6,7-THX (2). Final structure assignment of the natural Hypericum THX constituents was accomplished by comparing chromatographic and spectroscopic data (LC/MSn and GC/MS) with those of 1 and 2 which were obtained by synthesis. Beyond, investigations into the seeds of H. perforatum and H. tetrapterum by scanning electron microscopy (SEM) provided insights of the structure of the testa (seed coat), which is established by two cell layers, with the lignified sclerenchyma presumably being the depository of the xanthones.

Progressive pulmonary fibrosis in patients with connective tissue disease-associated interstitial lung disease: An explorative study.

Objectives: The aim of this study was to identify differences and similarities between connective tissue disease (CTD) patients with and without progressive pulmonary fibrosis (PPF) by applying the new guidelines. Patients and methods: Patient characteristics and disease courses from medical records of 50 CTD-associated Interstitial lung disease (ILD) patients (33 females, 17 males; mean age: 60.1±12.9 years) were longitudinally studied between January 2018 and May 2022. Respiratory involvement in CTD patients was described, and differences in CTD patients who developed PPF compared to those who did not were identified by the 2022 ATS (American Thoracic Society)/ERS (European Respiratory Society)/JRS (Japanese Respiratory Society)/ALAT (Asociación Latinoamericana de Thórax) Guidelines on Idiopathic Pulmonary Fibrosis and Progressive Pulmonary Fibrosis in Adults. Results: In the majority (74%) of patients, CTD was diagnosed before ILD onset. Nonspecific interstitial pneumonia was the most common high resolution computer tomography pattern, followed by the usual interstitial pneumonia pattern. On pulmonary function test, 38% had a restrictive pattern at baseline. Patients without PPF tended to have worse lung function at baseline and increased macrophage count in bronchoalveolar lavage than patients with PPF. Conclusion: In patients without PPF, disease progression may be missed, resulting in inadequate management. Interdisciplinary management of patients with CTD with the participation of pulmonologists and precise lung function diagnostics is recommended.

Early detection of tuberculosis: a systematic review.

Tuberculosis remains a significant global health challenge. Tuberculosis affects millions of individuals worldwide. Early detection of tuberculosis plays a relevant role in the management of treatment of tuberculosis. This systematic review will analyze the findings of several published studies on the topic of the early detection of tuberculosis. This systematic review highlights their methodologies and limitations as well as their contributions to our understanding of this pressing issue. Early detection of tuberculosis can be achieved through tuberculosis screening for contacts. Comprehensive health education for household contacts can be used as early detection. The in-house deep learning models can be used in the X-ray used for automatic detection of tuberculosis. Interferon gamma release assay, routine passive and active case detection, portable X-ray and nucleic acid amplification testing, and highly sensitive enzyme-linked immunosorbent assay tests play critical roles in improving tuberculosis detection.

Clinical relevance of positively determined myositis antibodies in rheumatology: a retrospective monocentric analysis.

BACKGROUND: The increased availability of myositis autoantibodies represents new possibilities and challenges in clinical practice (Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, de Visser M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017;76:1955-64. https://doi.org/10.1136/annrheumdis-2017-211468 .). The aim of this study was to perform a retrospective data analysis of patient cases with positive myositis autoantibodies to analyse their significance in routine rheumatology practice. METHODS: A monocentric analysis of all the orders used to determine myositis autoantibodies from July 2019 to May 2022 in the Department of Rheumatology, Krankenhaus Porz am Rhein, Cologne, Germany, was carried out. RESULTS: In the defined time interval, a total of 71,597 laboratory values for the antibodies mentioned above were obtained. A total of 238 different positive autoantibodies ​​were detected in 209 patients. Idiopathic inflammatory myopathy was diagnosed in 37 patients (18%), and inflammatory rheumatic diseases other than idiopathic inflammatory myopathy were diagnosed in 90 patients (43%). No inflammatory rheumatic disease was diagnosed in 82 patients (39%). General clusters of clinical manifestations were observed. CONCLUSIONS: In our cohort, we were able to show that a relevant proportion of patients with positive myositis antibodies did not have idiopathic inflammatory myopathies or inflammatory rheumatic diseases. This finding indicates the importance of myositis autoantibodies in this group of patients. However, further studies on the course of symptoms and examination results in patients without inflammatory rheumatic diseases and with positive myositis antibodies are necessary.

A clinical phenotype of VEXAS syndrome with pleural effusion, infiltrates, and systemic inflammation in a 76-year-old patient: a case report.

INTRODUCTION: VEXAS syndrome, characterized by a UBA1 gene mutation, is a rare and severe systemic inflammatory disease predominantly affecting men. Since its initial description in 2020, it has been noted for its broad clinical phenotype and frequent misdiagnosis. CASE PRESENTATION: A 76-year-old Caucasian male patient diagnosed with VEXAS syndrome is presented in this case report. He presented with typical symptoms including pulmonary manifestations (infiltrates and effusions), systemic inflammation, and haematological abnormalities. The diagnosis was challenging due to the disease's heterogeneous presentation, often resembling autoimmune or haematological diseases. This patient's case featured ground-glass opacities and pleural effusions, underlining the significant pulmonary involvement seen in 50-67% of VEXAS patients. His condition was further complicated by recurrent fever and systemic inflammation affecting multiple organs. CONCLUSION: VEXAS syndrome demands an aggressive treatment approach due to its high mortality rate and refractory nature. This case underscores the importance of including VEXAS syndrome in differential diagnoses, particularly for patients with systemic inflammation and pulmonary symptoms, and calls for multidisciplinary management and extensive research to understand its full range of clinical phenotypes.

The threat of disease increases as species move toward extinction.

At local scales, infectious disease is a common driver of population declines, but globally it is an infrequent contributor to species extinction and endangerment. For species at risk of extinction from disease important questions remain unanswered, including when does disease become a threat to species and does it co-occur, predictably, with other threats? Using newly compiled data from the International Union for Conservation of Nature (IUCN) Red List, we examined the relative role and co-occurrence of threats associated with amphibians, birds, and mammals at 6 levels of extinction risk (i.e., Red List status categories: least concern, near threatened, vulnerable, endangered, critically endangered, and extinct in the wild/extinct). We tested the null hypothesis that the proportion of species threatened by disease is the same in all 6 Red List status categories. Our approach revealed a new method for determining when disease most frequently threatens species at risk of extinction. The proportion of species threatened by disease varied significantly between IUCN status categories and linearly increased for amphibians, birds, and all species combined as these taxa move from move from least concern to critically endangered. Disease was infrequently the single contributing threat. However, when a species was negatively affected by a major threat other than disease (e.g., invasive species, land-use change) that species was more likely to be simultaneously threatened by disease than species that had no other threats. Potential drivers of these trends include ecological factors, clustering of phylogenetically related species in Red List status categories, discovery bias among species at greater risk of extinction, and availability of data. We echo earlier calls for baseline data on the presence of parasites and pathogens in species when they show the first signs of extinction risk and arguably before. La Amenaza de Enfermedades Incrementa a Medida que las Especies se Aproximan a la Extinción.

[Treatment alternatives for amyopathic MDA5-positive dermatomyositis]. / Therapiealternativen bei amyopathischer MDA5-positiver Dermatomyositis.

We report a case of an atypical course of therapy in amyopathic MDA5-antibody-positive dermatomyositis with interstitial lung disease. Due to the poor prognosis, early therapy with cyclophosphamide followed by rituximab was carried out initially in addition to the administration of prednisolone. Due to therapy failure, treatment was switched to mycophenolate mofetil. This showed a surprisingly rapid positive course in terms of interstitial lung disease, skin manifestation, and general disease activity.

The use of digital web-based video training for correct inhalation technique during the COVID-19 pandemic.

Scientifically validated web-based training videos for proper inhalation technique were increasingly used by an international audience during the pandemic. Translations into additional languages would support a larger patient population. https://bit.ly/3lYQwsD.

Clinical Outcomes of Intensity Modulated Proton Therapy Reirradiation for Gynecologic Malignancies.

Purpose: Pelvic reirradiation (re-RT) for patients with gynecologic cancers remains a challenge because of toxicity concerns. Given the dosimetric advantages of proton therapy, we aimed to assess oncologic and toxicity outcomes of patients with re-RT to the pelvis/abdomen with intensity modulated proton therapy (IMPT) for gynecologic cancers. Methods and Materials: We performed a retrospective analysis of all patients with gynecologic cancer treated at a single institution between 2015 and 2021 with IMPT re-RT. Patients were included for analysis if the IMPT plan had at least partial overlap with the treated volume of a previous radiation treatment. Results: A total of 29 patients were included for analysis, with 30 total courses of re-RT. The majority of patients had been treated previously with conventional fractionation to a median dose of 49.2 Gy (30-61.6 Gy). With a median follow-up of 23 months, 1-year local control was 83.5% and overall survival was 65.7%. Three patients (10%) developed acute and late grade 3 toxicity. One-year freedom from late grade 3+ toxicity was 96.3%. Conclusions: This is the first complete analysis of clinical outcomes for re-RT with IMPT for gynecologic malignancies. We demonstrate excellent local control and acceptable acute and late toxicity. IMPT should strongly be considered for treatments requiring re-RT for gynecologic malignancies.