Transcatheter Closure of Patent Ductus Arteriosus via Different Approaches

Background: There have been marked advances in devices such as Amplatzer Duct Occluder II (ADO-II) or vascular plug through 5Fr delivery sheath for closure of patent ductus arteriosus (PDA) in the past five decades, making it possible for cardiologists to deliver occluders via different approaches. However, comparisons of these different approaches have not been reported. Therefore, the aim of this study was to summarize and compare the advantages of different approaches for PDA closure, and to guide clinical strategies.Methods: This retrospective study included all patients undergoing transcatheter closure of PDA from 2019 to 2020. Patients were matched by 1:1 propensity score matching (PSM). The retrograde femoral artery approach (FAA) and simple vein approach (SVA) groups were compared with the conventional arteriovenous approach (CAA).Results: The average age of the 476 patients was 21.05 ± 21.15 years. Their average weight was 38.23 ± 24.1 kg and average height was 130.14 ± 34.45 cm. The mean diameter of the PDA was 4.29 ± 2.25 mm. There were 127 men and 349 women, comprising 205 adults and 271 children. Among them, 197 patients underwent CAA, 223 underwent SVA, and 56 underwent retrograde FAA. The diameter in the FAA group was smaller than that in the other two groups, but was similar in adults and children. In the PSM comparison of CAA and SVA, 136 patients with CAA and 136 patients with SVA were recruited. Simple vein approach was associated with markedly reduced length of hospital stay, length of operation, and contrast medium usage as compared with CAA (all P < 0.05). In the PSM comparison of FAA and CAA, 30 patients with CAA and 30 patients with FAA were recruited. The operation duration was longer in the CAA than in the FAA group. There were no significant differences in postoperative complications among groups.Conclusion: Patent ductus arteriosus closure by using the SVA and FAA is safe and effective, and has certain advantages in some respects as compared with CAA.

Extracellular Vesicles as a New Promising Therapy in HIV Infection

Combination antiretroviral therapy (cART) effectively blocks HIV replication but cannot completely eliminate HIV from the body mainly due to establishment of a viral reservoir. To date, clinical strategies designed to replace cART for life and alternatively to eliminate the HIV reservoir have failed. The reduced expression of viral antigens in the latently infected cells is one of the main reasons behind the failure of the strategies to purge the HIV reservoir. This situation has forced the scientific community to search alternative therapeutic strategies to control HIV infection. In this regard, recent findings have pointed out extracellular vesicles as therapeutic agents with enormous potential to control HIV infection. This review focuses on their role as pro-viral and anti-viral factors, as well as their potential therapeutic applications.

Neutrophils and Platelets: Immune Soldiers Fighting Together in Stroke Pathophysiology

Neutrophils and platelets exhibit a diverse repertoire of functions in thromboinflammatory conditions such as stroke. Most cerebral ischemic events result from longstanding chronic inflammation secondary to underlying pathogenic conditions, e.g., hypertension, diabetes mellitus, obstructive sleep apnea, coronary artery disease, atrial fibrillation, morbid obesity, dyslipidemia, and sickle cell disease. Neutrophils can enable, as well as resolve, cerebrovascular inflammation via many effector functions including neutrophil extracellular traps, serine proteases and reactive oxygen species, and pro-resolving endogenous molecules such as Annexin A1. Like neutrophils, platelets also engage in pro- as well as anti-inflammatory roles in regulating cerebrovascular inflammation. These anucleated cells are at the core of stroke pathogenesis and can trigger an ischemic event via adherence to the hypoxic cerebral endothelial cells culminating in aggregation and clot formation. In this article, we review and highlight the evolving role of neutrophils and platelets in ischemic stroke and discuss ongoing preclinical and clinical strategies that may produce viable therapeutics for prevention and management of stroke.

Finding Goal Focus With People With Severe Traumatic Brain Injury in a Person-Centered Multi-Component Community Connection Program (M-ComConnect)

Background and Objectives: Loss of social connections in the community is a common consequence of severe traumatic brain injury (TBI), resulting in reduced well-being and quality of life. M-ComConnect is an individualized multi-component community connection intervention with the key objectives of increasing social activity, developing social relationships, and supporting community participation following severe TBI. As part of the M-ComConnect approach, semi-structured initial interviews were conducted to develop a holistic understanding of each participant and their goal focus for the project. In this paper we describe how clinicians worked with participants to identify a desired community-based social activity in which to participate.Method: Transcripts of initial interviews between participant and clinician were analyzed using the phases of reflexive thematic analysis developed by Braun and Clarke. Participants were ten individuals aged between 24 and 75 with severe TBI. All were living in the community and reported reduced social connections since their TBI. The aim of the analysis was to evaluate the skills and strategies used by clinicians in their interactions with participants to derive goal focus for the program.Results: Thematic analysis of initial interview data revealed three main categories and fourteen sub-categories of clinical strategies. These were: (1) Humanizing (curiosity; demonstrating respect and empathy; providing compliments and affirmations; simple reflections; revealing aspects of self; and humor and laughter), (2) Empowering (emphasizing choice and control; highlighting strengths; identifying roadblocks and reframing to reveal opportunities; and collaborative problem solving), and (3) Focusing (making suggestions; identifying preferences; working with ideas; and negotiating). These strategies aligned with the program's relational approach and supported the core processes of the goal-focussing framework, namely understanding and connecting with you, building a relationship, and working together with you to find focus.Conclusion: The goal-focusing framework and clinical strategies outlined provide guidance for clinicians working with people with TBI in the community and is a promising way to engage clients when focusing on individualized social activity-based goals.

The Colorectal Cancer Tumor Microenvironment and Its Impact on Liver and Lung Metastasis

Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer-related mortality worldwide. A total of 20% of CRC patients present with distant metastases, most frequently to the liver and lung. In the primary tumor, as well as at each metastatic site, the cellular components of the tumor microenvironment (TME) contribute to tumor engraftment and metastasis. These include immune cells (macrophages, neutrophils, T lymphocytes, and dendritic cells) and stromal cells (cancer-associated fibroblasts and endothelial cells). In this review, we highlight how the TME influences tumor progression and invasion at the primary site and its function in fostering metastatic niches in the liver and lungs. We also discuss emerging clinical strategies to target the CRC TME.

Rapidly Growing Mycobacterium Species: The Long and Winding Road from Tuberculosis Vaccines to Potent Stress-Resilience Agents

Inflammatory diseases and stressor-related psychiatric disorders, for which inflammation is a risk factor, are increasing in modern Western societies. Recent studies suggest that immunoregulatory approaches are a promising tool in reducing the risk of suffering from such disorders. Specifically, the environmental saprophyte Mycobacterium vaccae National Collection of Type Cultures (NCTC) 11659 has recently gained attention for the prevention and treatment of stress-related psychiatric disorders. However, effective use requires a sophisticated understanding of the effects of M. vaccae NCTC 11659 and related rapidly growing mycobacteria (RGMs) on microbiome–gut–immune–brain interactions. This historical narrative review is intended as a first step in exploring these mechanisms and provides an overview of preclinical and clinical studies on M. vaccae NCTC 11659 and related RGMs. The overall objective of this review article is to increase the comprehension of, and interest in, the mechanisms through which M. vaccae NCTC 11659 and related RGMs promote stress resilience, with the intention of fostering novel clinical strategies for the prevention and treatment of stressor-related disorders.

Potential of E3 Ubiquitin Ligases in Cancer Immunity: Opportunities and Challenges

Cancer immunotherapies, including immune checkpoint inhibitors and immune pathway–targeted therapies, are promising clinical strategies for treating cancer. However, drug resistance and adverse reactions remain the main challenges for immunotherapy management. The future direction of immunotherapy is mainly to reduce side effects and improve the treatment response rate by finding new targets and new methods of combination therapy. Ubiquitination plays a crucial role in regulating the degradation of immune checkpoints and the activation of immune-related pathways. Some drugs that target E3 ubiquitin ligases have exhibited beneficial effects in preclinical and clinical antitumor treatments. In this review, we discuss mechanisms through which E3 ligases regulate tumor immune checkpoints and immune-related pathways as well as the opportunities and challenges for integrating E3 ligases targeting drugs into cancer immunotherapy.

On prediction of aided behavioural measures using speech auditory brainstem responses and decision trees

Current clinical strategies to assess benefits from hearing aids (HAs) are based on self-reported questionnaires and speech-in-noise (SIN) tests; which require behavioural cooperation. Instead, objective measures based on Auditory Brainstem Responses (ABRs) to speech stimuli would not require the individuals’ cooperation. Here, we re-analysed an existing dataset to predict behavioural measures with speech-ABRs using regression trees. Ninety-two HA users completed a self-reported questionnaire (SSQ-Speech) and performed two aided SIN tests: sentences in noise (BKB-SIN) and vowel-consonant-vowels (VCV) in noise. Speech-ABRs were evoked by a 40 ms [da] and recorded in 2x2 conditions: aided vs. unaided and quiet vs. background noise. For each recording condition, two sets of features were extracted: 1) amplitudes and latencies of speech-ABR peaks, 2) amplitudes and latencies of speech-ABR F0 encoding. Two regression trees were fitted for each of the three behavioural measures with either feature set and age, digit-span forward and backward, and pure tone average (PTA) as possible predictors. The PTA was the only predictor in the SSQ-Speech trees. In the BKB-SIN trees, performance was predicted by the aided latency of peak F in quiet for participants with PTAs between 43 and 61 dB HL. In the VCV trees, performance was predicted by the aided F0 encoding latency and the aided amplitude of peak VA in quiet for participants with PTAs ≤ 47 dB HL. These findings indicate that PTA was more informative than any speech-ABR measure, as these were relevant only for a subset of the participants. Therefore, speech-ABRs evoked by a 40 ms [da] are not a clinical predictor of behavioural measures in HA users.