-
Turk Gogus Kalp Damar Cerrahisi Dergisi May 2023Double sleeve lung resections are complex surgical procedures that require specialized surgical expertise and careful patient selection. These procedures allow for the... (Review)
Review
Double sleeve lung resections are complex surgical procedures that require specialized surgical expertise and careful patient selection. These procedures allow for the preservation of lung tissue while still achieving complete tumor resection for central tumors. Although initially considered high-risk operations, double sleeve lung resections have become a viable option for central tumors. Recent studies have shown that double sleeve lung resections are associated with lower morbidity and mortality rates than pneumonectomy. Furthermore, double sleeve lung resections may be associated with similar or even better long-term oncological outcomes compared to pneumonectomy, with the added benefit of preserving lung parenchyma and reducing the incidence of postoperative complications.
PubMed: 38344125
DOI: 10.5606/tgkdc.dergisi.2023.24754 -
BioRxiv : the Preprint Server For... Apr 2023The inability of antibodies and other biologics to penetrate the blood-brain barrier (BBB) is a key limitation to their use in diagnostic, imaging, and therapeutic...
The inability of antibodies and other biologics to penetrate the blood-brain barrier (BBB) is a key limitation to their use in diagnostic, imaging, and therapeutic applications. One promising strategy is to deliver IgGs using a bispecific BBB shuttle, which involves fusing an IgG with a second affinity ligand that engages a cerebrovascular endothelial target and facilitates transport across the BBB. Nearly all prior efforts have focused on the transferrin receptor (TfR-1) as the prototypical endothelial target despite inherent delivery and safety challenges. Here we report bispecific antibody shuttles that engage CD98hc (also known as 4F2 and SLC3A2), the heavy chain of the large neutral amino acid transporter (LAT1), and efficiently transport IgGs into the brain parenchyma. Notably, CD98hc shuttles lead to much longer-lived brain retention of IgGs than TfR-1 shuttles while enabling more specific brain targeting due to limited CD98hc engagement in the brain parenchyma. We demonstrate the broad utility of the CD98hc shuttles by reformatting three existing IgGs as CD98hc bispecific shuttles and delivering them to the mouse brain parenchyma that either agonize a neuronal receptor (TrkB) or target other endogenous antigens on specific types of brain cells (neurons and astrocytes).
PubMed: 37162883
DOI: 10.1101/2023.04.29.538811 -
International Journal of Surgery... Oct 2020Modern liver surgeon must be equipped with excellent theoretical and clinical skills to perform a perfect liver resection. A particular and growing relevance is devoted... (Review)
Review
Modern liver surgeon must be equipped with excellent theoretical and clinical skills to perform a perfect liver resection. A particular and growing relevance is devoted to parenchyma sparing liver surgery (PSS). Indeed, reducing the sacrifice of functioning parenchyma is one of the keys of a successful surgery, once oncological issues are properly addressed. Intraoperative ultrasound together with oncological and anatomical new insights have enhanced the possibility to offer PSS even in advanced disease usually afforded with major resections or staged procedures or even considered unresectable. These complex hepatectomies are mainly performed with open surgery, while major or staged procedures could be faced with minimal access liver surgery (MALS): that is generating a potential conflict between open PSS and MALS major hepatectomies. An overall evaluation of oncological radicality, safety, salvageability, and quality of life suggest to prioritize PSS, which is always minimal invasive liver surgery in a hepatic-centered perspective, while MALS is not.
Topics: Colorectal Neoplasms; Hepatectomy; Humans; Liver; Liver Neoplasms; Organ Sparing Treatments; Quality of Life; Ultrasonography
PubMed: 32335245
DOI: 10.1016/j.ijsu.2020.04.047 -
Frontiers in Immunology 2017Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive deterioration of cognitive functions. Its neuropathological features include... (Review)
Review
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive deterioration of cognitive functions. Its neuropathological features include amyloid-β (Aβ) accumulation, the formation of neurofibrillary tangles, and the loss of neurons and synapses. Neuroinflammation is a well-established feature of AD pathogenesis, and a better understanding of its mechanisms could facilitate the development of new therapeutic approaches. Recent studies in transgenic mouse models of AD have shown that neutrophils adhere to blood vessels and migrate inside the parenchyma. Moreover, studies in human AD subjects have also shown that neutrophils adhere and spread inside brain vessels and invade the parenchyma, suggesting these cells play a role in AD pathogenesis. Indeed, neutrophil depletion and the therapeutic inhibition of neutrophil trafficking, achieved by blocking LFA-1 integrin in AD mouse models, significantly reduced memory loss and the neuropathological features of AD. We observed that neutrophils release neutrophil extracellular traps (NETs) inside blood vessels and in the parenchyma of AD mice, potentially harming the blood-brain barrier and neural cells. Furthermore, confocal microscopy confirmed the presence of NETs inside the cortical vessels and parenchyma of subjects with AD, providing more evidence that neutrophils and NETs play a role in AD-related tissue destruction. The discovery of NETs inside the AD brain suggests that these formations may exacerbate neuro-inflammatory processes, promoting vascular and parenchymal damage during AD. The inhibition of NET formation has achieved therapeutic benefits in several models of chronic inflammatory diseases, including autoimmune diseases affecting the brain. Therefore, the targeting of NETs may delay AD pathogenesis and offer a novel approach for the treatment of this increasingly prevalent disease.
PubMed: 28303140
DOI: 10.3389/fimmu.2017.00211 -
Frontiers in Cell and Developmental... 2023The central nervous system (CNS) is considered as an immune privilege organ, based on experiments in the mid 20th century showing that the brain fails to mount an... (Review)
Review
The central nervous system (CNS) is considered as an immune privilege organ, based on experiments in the mid 20th century showing that the brain fails to mount an efficient immune response against an allogeneic graft. This suggests that in addition to the presence of the blood-brain barrier (BBB), the apparent absence of classical lymphatic vasculature in the CNS parenchyma limits the capacity for an immune response. Although this view is partially overturned by the recent discovery of the lymphatic-like hybrid vessels in the Schlemm's canal in the eye and the lymphatic vasculature in the outmost layer of the meninges, the existence of lymphatic vessels in the CNS parenchyma has not been reported. Two potential mechanisms by which lymphatic vasculature may arise in the organs are: 1) sprouting and invasion of lymphatic vessels from the surrounding tissues into the parenchyma and 2) differentiation of blood endothelial cells into lymphatic endothelial cells in the parenchyma. Considering these mechanisms, we here discuss what causes the dearth of lymphatic vessels specifically in the CNS parenchyma.
PubMed: 37091974
DOI: 10.3389/fcell.2023.1150775