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1.
Respiration ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38870914

ABSTRACT

Introduction Persistent air leak (PAL) is associated with prolonged hospitalization, high morbidity and increased treatment costs. Conservative treatment consists of observation, chest tube drainage and pleurodesis. Guidelines recommend surgical evaluation if air leak does not respond after 3-5 days. One-way endobronchial valves (EBV) have been proposed as a treatment option for patients with PAL in which surgical treatment is not feasible, high risk or has failed. We aimed to provide a comprehensive overview of reported EBV use for PAL and issue best practice recommendations based on multicenter experience. Methods We conducted a retrospective observational case-series study at four different European academic hospitals and provided best practice recommendations based on our experience. A systematic literature review was performed to summarize the current knowledge on EBV in PAL. Results We enrolled 66 patients, male (66.7%), median age 59.5 years. The most common underlying lung disease was chronic obstructive pulmonary disease (39.4%), and lung cancer (33.3%). The median time between pneumothorax and valve placement was 24.5 days (IQR: 14.0-54.3). Air leak resolved in 40/66 patients (60.6%) within thirty days after endobronchial valve treatment. Concerning safety outcome, no procedure related mortality was reported and complication rate was low (6.1%). 5 patients (7.6%) died in the first 30 days after intervention. Conclusion EBV placement is a treatment option in patients with persistent air leak (PAL). In this multicenter case-series of high risk patients not eligible for lung surgery, we show that EBV placement resulted in air leak resolution in 6 out of 10 patients with a low complication rate. Considering the minimally invasive nature of EBV to treat PAL as opposed to surgery, further research should investigate if EBV treatment should be expanded in low to intermediate risk PAL patients.

2.
Respiration ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38870924

ABSTRACT

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) and emphysema experience malnutrition and pulmonary cachexia. Endoscopic lung volume reduction (ELVR) with endobronchial valves has not only improved lung function, exercise capacity, and quality of life, but also influenced body weight. Only a few data are available on body composition changes after ELVR. METHODS: This single-center prospective study of patients with advanced COPD investigates body composition before and after endoscopic valve treatment using multifrequency bioelectrical impedance analysis (BIA). The following parameters were evaluated in addition to clinical data and routine tests: body weight, body mass index (BMI), basal metabolic rate, total body water, body fat, cell percentage, phase angle, intracellular water (ICW), extracellular water (ECW), extracellular mass (ECM), body cell mas (BCM), lean body mass (LBM = ECM + BCM) and fat-free mass index. RESULTS: A total of 23 patients (mean emphysema index 37.2 ± 7.5 %, BMI 23.4 ± 4.3 kg/m²) experienced improvements in lung function and exercise capacity with ELVR. Complete lobar atelectasis was achieved in 39.1% of participants. A non-statistically significant increase in body weight and BMI was observed after ELVR (p = 0.111 and p = 0.102). BIA measurement revealed a worsening of phase angle, cell percentage and ECM/BCM and thus of body composition, but without statistical significance. This is mainly due to a statistically significant increase in ECM, ECW, and ICW (all p < 0.001). CONCLUSION: ELVR demonstrated no beneficial changes in body composition, although patients tend to gain weight. A larger cohort is warranted to confirm these findings. .

3.
Trends Parasitol ; 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38853076

ABSTRACT

Mosquitoes are important vectors for human diseases, transmitting pathogens that cause a range of parasitic and viral infections. Mosquito blood-feeding is heterogeneous, meaning that some human hosts are at higher risk of receiving bites than others, and this heterogeneity is multifactorial. Mosquitoes integrate specific cues to locate their hosts, and mosquito attraction differs considerably between individual human hosts. Heterogeneous mosquito biting results from variations in both host attractiveness and availability and can impact transmission of vector-borne diseases. However, the extent and drivers of this heterogeneity and its importance for pathogen transmission remain incompletely understood. Here, we review methods and recent data describing human characteristics that affect host-seeking behavior and host preferences of mosquito disease vectors, and the implications for vector-borne disease transmission.

4.
Ther Adv Respir Dis ; 18: 17534666241253694, 2024.
Article in English | MEDLINE | ID: mdl-38803144

ABSTRACT

BACKGROUND: Given the rarity of tracheobronchopathia osteochondroplastica (TO), many young doctors in primary hospitals are unable to identify TO based on bronchoscopy findings. OBJECTIVES: To build an artificial intelligence (AI) model for differentiating TO from other multinodular airway diseases by using bronchoscopic images. DESIGN: We designed the study by comparing the imaging data of patients undergoing bronchoscopy from January 2010 to October 2022 by using EfficientNet. Bronchoscopic images of 21 patients with TO at Anhui Chest Hospital from October 2019 to October 2022 were collected for external validation. METHODS: Bronchoscopic images of patients with multinodular airway lesions (including TO, amyloidosis, tumors, and inflammation) and without airway lesions in the First Affiliated Hospital of Guangzhou Medical University were collected. The images were randomized (4:1) into training and validation groups based on different diseases and utilized for deep learning by convolutional neural networks (CNNs). RESULTS: We enrolled 201 patients with multinodular airway disease (38, 15, 75, and 73 patients with TO, amyloidosis, tumors, and inflammation, respectively) and 213 without any airway lesions. To find multinodular lesion images for deep learning, we utilized 2183 bronchoscopic images of multinodular lesions (including TO, amyloidosis, tumor, and inflammation) and compared them with images without any airway lesions (1733). The accuracy of multinodular lesion identification was 98.9%. Further, the accuracy of TO detection based on the bronchoscopic images of multinodular lesions was 89.2%. Regarding external validation (using images from 21 patients with TO), all patients could be diagnosed with TO; the accuracy was 89.8%. CONCLUSION: We built an AI model that could differentiate TO from other multinodular airway diseases (mainly amyloidosis, tumors, and inflammation) by using bronchoscopic images. The model could help young physicians identify this rare airway disease.


Subject(s)
Bronchoscopy , Osteochondrodysplasias , Predictive Value of Tests , Tracheal Diseases , Humans , Tracheal Diseases/diagnostic imaging , Tracheal Diseases/pathology , Tracheal Diseases/diagnosis , Middle Aged , Male , Female , Adult , Diagnosis, Differential , Osteochondrodysplasias/diagnostic imaging , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/pathology , Reproducibility of Results , Deep Learning , Aged , China , Image Interpretation, Computer-Assisted , Neural Networks, Computer , Artificial Intelligence
5.
Arch Microbiol ; 206(6): 285, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38816572

ABSTRACT

Intracellular pathogens like Brucella face challenges during the intraphagocytic adaptation phase, where the modulation of gene expression plays an essential role in taking advantage of stressors to persist inside the host cell. This study aims to explore the expression of antisense virB2 RNA strand and related genes under intracellular simulation media. Sense and antisense virB2 RNA strands increased expression when nutrient deprivation and acidification were higher, being starvation more determinative. Meanwhile, bspB, one of the T4SS effector genes, exhibited the highest expression during the exposition to pH 4.5 and nutrient abundance. Based on RNA-seq analysis and RACE data, we constructed a regional map depicting the 5' and 3' ends of virB2 and the cis-encoded asRNA_0067. Without affecting the CDS or a possible autonomous RBS, we generate the deletion mutant ΔasRNA_0067, significantly reducing virB2 mRNA expression and survival rate. These results suggest that the antisense asRNA_0067 expression is promoted under exposure to the intraphagocytic adaptation phase stressors, and its deletion is associated with a lower transcription of the virB2 gene. Our findings illuminate the significance of these RNA strands in modulating the survival strategy of Brucella within the host and emphasize the role of nutrient deprivation in gene expression.


Subject(s)
Brucella abortus , Gene Expression Regulation, Bacterial , Brucella abortus/genetics , Brucella abortus/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , RNA, Bacterial/genetics , RNA, Bacterial/metabolism , Transcription, Genetic , RNA, Antisense/genetics , RNA, Antisense/metabolism , Stress, Physiological , Animals , Macrophages/microbiology
6.
Nat Commun ; 15(1): 4384, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38782917

ABSTRACT

Biopolymers such as nucleic acids and proteins exhibit dynamic backbone folding, wherein site-specific intramolecular interactions determine overall structure. Proteins then hierarchically assemble into supramolecular polymers such as microtubules, that are robust yet dynamic, constantly growing or shortening to adjust to cellular needs. The combination of dynamic, energy-driven folding and growth with structural stiffness and length control is difficult to achieve in synthetic polymer self-assembly. Here we show that highly charged, monodisperse DNA-oligomers assemble via seeded growth into length-controlled supramolecular fibers during heating; when the temperature is lowered, these metastable fibers slowly disassemble. Furthermore, the specific molecular structures of oligomers that promote fiber formation contradict the typical theory of block copolymer self-assembly. Efficient curling and packing of the oligomers - or 'curlamers' - determine morphology, rather than hydrophobic to hydrophilic ratio. Addition of a small molecule stabilises the DNA fibers, enabling temporal control of polymer lifetime and underscoring their potential use in nucleic-acid delivery, stimuli-responsive biomaterials, and soft robotics.


Subject(s)
DNA , Hot Temperature , Polymers , DNA/chemistry , Polymers/chemistry , Hydrophobic and Hydrophilic Interactions
7.
Int J Cancer ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783577

ABSTRACT

Management of multiple primary lung cancer (MPLC) remains challenging, partly due to its increasing incidence, especially with the significant rise in cases of multiple lung nodules caused by low-dose computed tomography screening. Moreover, the indefinite pathogenesis, diagnostic criteria, and treatment selection add to the complexity. In recent years, there have been continuous efforts to dissect the molecular characteristics of MPLC and explore new diagnostic approaches as well as treatment modalities, which will be reviewed here, with a focus on newly emerging evidence and future perspectives, hope to provide new insights into the management of MPLC and serve as inspiration for future research related to MPLC.

8.
Nat Commun ; 15(1): 4028, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740738

ABSTRACT

In recent years, there has been a growing demand for drug design approaches that incorporate a higher number of sp3-hybridized carbons, necessitating the development of innovative cross-coupling strategies to reliably introduce aliphatic fragments. Here, we present a powerful approach for the light-mediated B-alkyl Suzuki-Miyaura cross-coupling between alkyl boranes and aryl bromides. Alkyl boranes were easily generated via hydroboration from readily available alkenes, exhibiting excellent regioselectivity and enabling the selective transfer of a diverse range of primary alkyl fragments onto the arene ring under photocatalytic conditions. This methodology eliminates the need for expensive catalytic systems and sensitive organometallic compounds, operating efficiently at room temperature within just 30 min. We further demonstrate the translation of the present protocol to continuous-flow conditions, enhancing scalability, safety, and overall efficiency of the method. This versatile approach offers significant potential for accelerating drug discovery efforts by enabling the introduction of complex aliphatic fragments in a straightforward and reliable manner.

9.
Mol Cell ; 84(10): 1980-1994.e8, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38759629

ABSTRACT

Aggregation of proteins containing expanded polyglutamine (polyQ) repeats is the cytopathologic hallmark of a group of dominantly inherited neurodegenerative diseases, including Huntington's disease (HD). Huntingtin (Htt), the disease protein of HD, forms amyloid-like fibrils by liquid-to-solid phase transition. Macroautophagy has been proposed to clear polyQ aggregates, but the efficiency of aggrephagy is limited. Here, we used cryo-electron tomography to visualize the interactions of autophagosomes with polyQ aggregates in cultured cells in situ. We found that an amorphous aggregate phase exists next to the radially organized polyQ fibrils. Autophagosomes preferentially engulfed this amorphous material, mediated by interactions between the autophagy receptor p62/SQSTM1 and the non-fibrillar aggregate surface. In contrast, amyloid fibrils excluded p62 and evaded clearance, resulting in trapping of autophagic structures. These results suggest that the limited efficiency of autophagy in clearing polyQ aggregates is due to the inability of autophagosomes to interact productively with the non-deformable, fibrillar disease aggregates.


Subject(s)
Amyloid , Autophagosomes , Autophagy , Huntingtin Protein , Huntington Disease , Peptides , Protein Aggregates , Sequestosome-1 Protein , Peptides/metabolism , Peptides/chemistry , Peptides/genetics , Humans , Huntingtin Protein/metabolism , Huntingtin Protein/genetics , Huntingtin Protein/chemistry , Autophagosomes/metabolism , Autophagosomes/ultrastructure , Sequestosome-1 Protein/metabolism , Sequestosome-1 Protein/genetics , Amyloid/metabolism , Amyloid/chemistry , Amyloid/genetics , Huntington Disease/metabolism , Huntington Disease/genetics , Huntington Disease/pathology , Cryoelectron Microscopy , Animals , Protein Aggregation, Pathological/metabolism , Protein Aggregation, Pathological/genetics
10.
Complement Med Res ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38744266

ABSTRACT

BACKGROUND: Neck reflex points or Adler-Langer Points are commonly used in neural therapy to detect so-called interference fields. Chronic irritations or inflammations in the sinuses, teeth, tonsils or ears are supposed to induce tension and tenderness of the soft tissues and short muscles in the upper cervical spine. The individual treatment strategy is based on the results of diagnostic Adler-Langer Points palpation. This study investigated the inter- and intra-rater reliability and explored treatment effects. METHODS: We performed a randomized-controlled trial with 104 inpatients (80.8% female, 51.812.74 yrs) of a German department for internal and integrative medicine. Patients were randomized to individual neural therapy according to the pathological findings (n=48) or no treatment (n=56). In each patient, three experienced raters (20-45y experience in neural therapy) and two novice raters (medical students) rated Adler-Langer Points rigidity on a standardized rating scale ("strong", "weak", "none"). The patients independently evaluated the tenderness on palpation of the eight points using the same scale. Pressure pain thresholds were assessed at the eight Adler-Langer Points. All patients were retested after 30 minutes. The five raters were blinded to treatment allocation and assessments of the other raters. Video recordings were obtained to assess the consistency of the areas tested by the different raters. RESULTS: Agreement between patients and raters (Cohen's Kappa=.161-.400) and inter-rater reliability were low (Fleiss-Kappa=.132-.150). Moreover, the individual agreement (pre-post comparisons in untreated patients) was similarly low even in experienced raters (Cohen's Kappa=.099-.173). Video documentation suggests that raters do not place their fingers in the correct segments (percentage of correct position 42.0-60.6%). Pressure pain thresholds at five of the eight Adler-Langer Points showed significant changes after treatment compared to none in the control group. CONCLUSION: Under this artificial experimental setting, this method of Adler-Langer Point palpation has not proven to be a reliable diagnostic tool. But it could be shown, that as claimed by the method, the tenderness in five of eight Adler-Langer Points decreased after neural therapy.

11.
Br J Soc Psychol ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38738819

ABSTRACT

Joint action theorizing implies that any coordinated behaviour that induces co-representation with a partner should increase social identification, especially when the associated actions require a high degree of coordination and are experienced as being performed effectively. The current research provides a first test of this new theoretical prediction for complementary (rather than synchronous) joint actions. In each of two pre-registered experiments establishing a novel paradigm, participants performed a digital joystick task with a joint performance goal with three different partners. The task varied in coordination requirements across partners. In Experiment 1, results showed that when task segments were discrete between partners, they identified less as a group than when they had to coordinate their behaviour. Surprisingly, although constant coordination increased co-representation relative to intermittent coordination, it did not correspondingly increase social identification. However, performance correlated positively with identification; as performance was worse when participants had to coordinate, this may explain the results. Experiment 2 showed that performance is causally linked to identification when coordination is necessary. Taken together, our results suggest that experiencing effective coordination leads to greater social identification. In general, paradigms capable of examining the perceptual and motor aspects of collective behaviour may offer a new perspective on social identification in general and the performance-identification link in particular.

12.
Respir Med ; 227: 107639, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38642906

ABSTRACT

Bronchoscopic lung volume reduction treatment with Zephyr one-way valves is an effective guideline-based treatment option for patients with severe emphysema and hyperinflation. However, in some cases the treatment response is less than anticipated or there might be a loss of initial treatment effect. Reasons for the lack of response can include incorrect assessment of collateral ventilation, improper valve placement, or patient related factors. Loss of initial benefit can be due to granulation tissue formation and subsequent valve dysfunction, or there may be side effects such as excessive coughing or infectious problems. Careful follow-up after treatment with valves is important and evaluation with a CT scan and/or bronchoscopy is helpful if there is no improvement after treatment or loss of initial benefit. This paper aims to describe the most important causes and provide a strategy of how to approach and manage these patients.


Subject(s)
Bronchoscopy , Pneumonectomy , Pulmonary Emphysema , Humans , Bronchoscopy/methods , Pulmonary Emphysema/surgery , Pulmonary Emphysema/physiopathology , Pneumonectomy/methods , Treatment Outcome , Tomography, X-Ray Computed
13.
Pharmacotherapy ; 44(6): 416-424, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38686648

ABSTRACT

BACKGROUND: Major bleeding occurs annually in 1%-3% of patients on vitamin K antagonists (VKAs), despite close monitoring. Genetic variants in proteins involved in VKA response may affect this risk. AIM: To determine the association of genetic variants (cytochrome P450 enzymes 2C9 [CYP2C9] and 4F2 [CYP4F2], gamma-glutamyl carboxylase [GGCX]) with major bleeding in VKA users, separately and combined, including vitamin K epoxide reductase complex subunit-1 (VKORC1). METHODS: A case-cohort study was established within the BLEEDS cohort, which includes 16,570 patients who initiated VKAs between 2012 and 2014. We selected all 326 major bleeding cases that occurred during 17,613 years of follow-up and a random subcohort of 978 patients. We determined variants in CYP2C9, CYP4F2, GGCX, VKORC1 and evaluated the interaction between variant genotypes. Hazard ratios for major bleeding with 95% confidence intervals (95% CI) were estimated by weighted Cox regression. RESULTS: Genotype was determined in 256 cases and 783 subcohort members. Phenprocoumon was the most prescribed VKA for both cases and the subcohort (78% and 75%, respectively). Patients with major bleeding were slightly older than subcohort patients. CYP4F2-TT carriership was associated with a 1.6-fold (95% CI 0.9-2.8) increased risk of major bleeding compared with CC-alleles, albeit not statistically significant. For the CYP2C9 and GGCX variants instead, the major bleeding risk was around unity. Carrying at least two variant genotypes in CYP2C9 (poor metabolizer), CYP4F2-TT, and VKORC1-AA was associated with a 4.0-fold (95%CI 1.4-11.4) increased risk, while carriers of both CYP4F2-TT and VKORC1-AA had a particularly increased major bleeding risk (hazard ratio 6.7, 95% CI 1.5-29.8) compared with carriers of CC alleles in CYP4F2 and GG in VKORC1. However, the number of major bleeding cases in carriers of multiple variants was few (8 and 5 patients, respectively). CONCLUSIONS: CYP4F2 polymorphism was associated with major bleeding, especially in combination with VKORC1 genetic variants. These variants could be considered to further personalize anticoagulant treatment.


Subject(s)
Anticoagulants , Hemorrhage , Polymorphism, Genetic , Vitamin K Epoxide Reductases , Vitamin K , Humans , Vitamin K/antagonists & inhibitors , Hemorrhage/chemically induced , Hemorrhage/genetics , Hemorrhage/epidemiology , Female , Male , Aged , Vitamin K Epoxide Reductases/genetics , Cohort Studies , Anticoagulants/adverse effects , Middle Aged , Cytochrome P-450 CYP2C9/genetics , Genotype , Cytochrome P450 Family 4/genetics , Aged, 80 and over , Carbon-Carbon Ligases/genetics , Case-Control Studies
14.
N Engl J Med ; 390(15): 1382-1393, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38587239

ABSTRACT

BACKGROUND: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.).


Subject(s)
Heart-Assist Devices , ST Elevation Myocardial Infarction , Shock, Cardiogenic , Aged , Female , Humans , Male , Heart-Assist Devices/adverse effects , Incidence , Shock, Cardiogenic/etiology , Shock, Cardiogenic/mortality , Shock, Cardiogenic/surgery , ST Elevation Myocardial Infarction/complications , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/therapy , Treatment Outcome , Assisted Circulation/adverse effects , Assisted Circulation/instrumentation , Assisted Circulation/methods
16.
BMC Med Educ ; 24(1): 420, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38641835

ABSTRACT

BACKGROUND: PRiVENT (PRevention of invasive VENTilation) is an evaluation of a bundle of interventions aimed at the prevention of long-term invasive mechanical ventilation. One of these elements is an e-learning course for healthcare professionals to improve weaning expertise. The aim of our analysis is to examine the implementation of the course in cooperating intensive care units. METHODS: The course has been developed through a peer review process by pulmonary and critical care physicians in collaboration with respiratory therapists, supported by health services researchers and a professional e-learning agency. The e-learning platform "weLearn" was made available online to participating healthcare professionals. Feedback on the e-learning programme was obtained and discussed in quality circles (QCs). We measured the acceptance and use of the programme through access statistics. RESULTS: The e-learning course "Joint Prevention of Long-Term Ventilation" consists of 7 separate modules with practice-oriented training units as well as a cross-module area and corresponding interactive case studies. Users can receive 23 CME (continuing medical education) credits. The platform was released on July 1, 2021. By June 28, 2023, 214 users from 33 clinics had registered. Most users (77-98%) completed the modules, thus performing well in the test, where 90-100% passed. In the QCs, the users commended the structure and practical relevance of the programme, as well as the opportunity to earn CME credits. CONCLUSION: Especially for medical staff in intensive care units, where continuous training is often a challenge during shift work, e-learning is a useful supplement to existing medical training. TRIAL REGISTRATION: The PRiVENT study is registered at ClinicalTrials.gov (NCT05260853) on 02/03/2022.


Subject(s)
Computer-Assisted Instruction , Humans , Ventilator Weaning , Learning , Health Personnel/education , Critical Care
17.
Biomarkers ; 29(4): 205-210, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38588595

ABSTRACT

BACKGROUND: Currently available risk scores fail to accurately predict morbidity and mortality in patients with severe symptomatic aortic stenosis who undergo transcatheter aortic valve implantation (TAVI). In this context, biomarkers like matrix metalloproteinase-2 (MMP-2) and Galectin-3 (Gal-3) may provide additional prognostic information. METHODS: Patients with severe aortic stenosis undergoing consecutive, elective, transfemoral TAVI were included. Baseline demographic data, functional status, echocardiographic findings, clinical outcomes and biomarker levels were collected and analysed. RESULTS: The study cohort consisted of 89 patients (age 80.4 ± 5.1 years, EuroScore II 7.1 ± 5.8%). During a median follow-up period of 526 d, 28 patients (31.4%) died. Among those who died, median baseline MMP-2 (alive: 221.6 [170.4; 263] pg/mL vs. deceased: 272.1 [225; 308.8] pg/mL, p < 0.001) and Gal-3 levels (alive: 19.1 [13.5; 24.6] pg/mL vs. deceased: 25 [17.6; 29.5] pg/mL, p = 0.006) were higher than in survivors. In ROC analysis, MMP-2 reached an acceptable level of discrimination to predict mortality (AUC 0.733, 95% CI [0.62; 0.83], p < 0.001), but the predictive value of Gal-3 was poor (AUC 0.677, 95% CI [0.56; 0.79], p = 0.002). Kaplan-Meier and Cox regression analyses showed that patients with MMP-2 and Gal-3 concentrations above the median at baseline had significantly impaired long-term survival (p = 0.004 and p = 0.02, respectively). CONCLUSIONS: In patients with severe aortic stenosis undergoing transfemoral TAVI, MMP-2 and to a lesser extent Gal-3, seem to have additive value in optimizing risk prediction and streamlining decision-making.


Subject(s)
Aortic Valve Stenosis , Biomarkers , Galectin 3 , Matrix Metalloproteinase 2 , Transcatheter Aortic Valve Replacement , Humans , Matrix Metalloproteinase 2/blood , Transcatheter Aortic Valve Replacement/mortality , Biomarkers/blood , Male , Female , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/mortality , Aortic Valve Stenosis/blood , Galectin 3/blood , Aged, 80 and over , Aged , Prognosis , Galectins , Blood Proteins/analysis , Blood Proteins/metabolism
18.
Biomacromolecules ; 25(5): 3163-3168, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38651279

ABSTRACT

Studies have shown that poly(adenine) DNA and RNA strands protonate at a low pH to form self-associating duplexes; however, the nanoscopic morphology of these structures is unclear. Here, we use Transition Electron Microscopy (TEM), Atomic Force Microscopy (AFM), dynamic light scattering (DLS), and fluorescence spectroscopy to show that both ribose identity (DNA or RNA) and assembly conditions (thermal or room-temperature annealing) dictate unique hierarchical structures for poly(adenine) sequences at a low pH. We show that while the thermodynamic product of protonating poly(adenine) DNA is a discrete dimer of two DNA strands, the kinetic product is a supramolecular polymer that branches and aggregates to form micron-diameter superstructures. In contrast, we find that protonated poly(A) RNA polymerizes into micrometer-length, twisted fibers under the same conditions. These divergent hierarchical morphologies highlight the amplification of subtle chemical differences between RNA and DNA into unique nanoscale behaviors. With the use of poly(adenine) strands spanning vaccine technologies, sensing, and dynamic biotechnology, understanding and controlling the underlying assembly pathways of these structures are critical to developing robust, programmable nanotechnologies.


Subject(s)
DNA , Poly A , RNA , RNA/chemistry , DNA/chemistry , Poly A/chemistry , Protons , Polymers/chemistry , Microscopy, Atomic Force , Hydrogen-Ion Concentration
19.
Respiration ; 103(6): 295-316, 2024.
Article in English | MEDLINE | ID: mdl-38498991

ABSTRACT

BACKGROUND: Lung tumors are prevalent malignancies associated with a high mortality rate, imposing significant medical and societal burdens. Although immunotherapy shows promise in improving survival, response rates are relatively modest. Thermal ablation can not only eliminate tumor cells directly but also enhance antitumor immunity response, thus manifesting a remarkable propensity to synergize with immunotherapy. SUMMARY: In this review, we provided a brief overview of the application of thermal ablation in peripheral lung tumors. We summarized the patient selection of thermal ablation. We highlighted the potential of thermal ablation to augment the antitumor immune response, offering a promising avenue for combined therapies. We summarized studies assessing the synergistic effects of thermal ablation and immunotherapy in preclinical and clinical settings. Lastly, we underscored the urgent issues that warrant in-depth exploration when applying thermal ablation and immunotherapy to lung tumor patients. KEY MESSAGES: This review emphasized the prospects of using thermal ablation combined with immunotherapy in patients with peripheral lung tumors. However, further research is needed to enhance and optimize this treatment strategy.


Subject(s)
Immunotherapy , Lung Neoplasms , Humans , Lung Neoplasms/therapy , Lung Neoplasms/immunology , Immunotherapy/methods , Combined Modality Therapy , Ablation Techniques/methods
20.
Transplantation ; 108(6): 1410-1416, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38548703

ABSTRACT

BACKGROUND: Normothermic liver machine perfusion (NLMP) is advancing the field of liver transplantation (LT). Beyond improved preservation and organ assessment, NLMP helps to increase organ utilization. We herein address the feasibility and merit of NLMP in split liver transplantation (SLT) to postpone the transplantation of the second split graft to the following day. METHODS: We analyzed the perfusion characteristics and outcomes of all consecutive adult recipients who underwent SLT following NLMP from February 1, 2018, to June 30, 2023. The primary endpoint was 90-d graft and patient survival. Secondary endpoints were posttransplant complications and 90-d morbidity. RESULTS: Three right and 3 extended right SLT following NLMP have been performed. NLMP was uneventful in all cases. Perfusion characteristics differed according to graft volume. Mean perfusion time was 17:00 h (±05:13) and bile production ranged between 8 and 21 mL/h. All split grafts fulfilled predefined center viability criteria during NLMP and were transplanted on the following day. The 90-d graft and patient survival rate was 100%. Three patients (50%) required an early relaparotomy, and 2 patients (33.3%) developed biliary complications. The 90-d morbidity as recorded by the comprehensive complication index was 62.7 (±24.7). CONCLUSIONS: NLMP of split liver grafts is technically feasible and safe. Through prolongation of preservation time, NLMP allows to safely postpone transplantation of the second split liver graft to the next day.


Subject(s)
Feasibility Studies , Graft Survival , Liver Transplantation , Organ Preservation , Perfusion , Humans , Liver Transplantation/methods , Liver Transplantation/adverse effects , Perfusion/methods , Male , Middle Aged , Female , Organ Preservation/methods , Adult , Treatment Outcome , Time Factors , Proof of Concept Study , Aged , Liver/surgery , Liver/blood supply , Retrospective Studies , Postoperative Complications/etiology
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