Ultrasonography-Guided Common Musculoskeletal Interventions from Head to Toe: Procedural Tips for General Radiologists

White Roland,Croft Michael,Bird Stephen,Sampson Matthew 대한영상의학회 2021 Korean Journal of Radiology Vol.22 No.12

The expanding scope of interventional musculoskeletal procedures has resulted in increased pressure on general radiologists. The confidence of general radiologists in performing ultrasound-guided musculoskeletal procedures varies with their clinical exposure. This didactic review provides a methodologically and clinically oriented approach to enhancing user understanding and confidence in performing ultrasound-guided musculoskeletal procedures. The body of the text is accompanied by figures depicting the procedural approach, injection site, and labeled ultrasonography images. This paper aims to provide a teaching and bedside aid for education on and the execution of musculoskeletal procedures to ensure the provision of quality health care.

Global Expanded Access Program for Pemigatinib in Patients with Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma and Fibroblast Growth Factor Receptor Gene Alterations

Anouk Lindley,Gerald Prager,Michael Bitzer,Timothy C. Burn,Christine F. Lihou,Elisabeth Croft 대한암학회 2024 Cancer Research and Treatment Vol.56 No.3

Purpose Pemigatinib is a fibroblast growth factor receptor-2 (FGFR2) inhibitor approved for use in patients with previously treated cholangiocarcinoma (CCA) and FGFR2 fusions or rearrangements. This ongoing global Expanded Access Program (EAP) allows physicians in regions where pemigatinib is not commercially available to request pemigatinib for patients with locally advanced or metastatic CCA who, in the physician’s opinion, could benefit from pemigatinib treatment. Materials and Methods Eighty-nine patients from Europe, North America, and Israel were treated from January 2020 through September 2021. Results Patients had FGFR gene fusions (68.5%), rearrangements (12.4%), translocations (5.6%), amplifications (2.2%), and other alterations (11.2%). Median duration of treatment in the EAP was 4.0 months (range, 0.1 to 13.6 months). The most frequently reported adverse event (AE) was hyperphosphatemia (22.5%); the most common serious AE was cholangitis (3.4%). Treatment discontinuation was associated with reports of AEs for seven patients (7.9%). AEs associated with pemigatinib were consistent with those observed in clinical trials. Conclusion Efficacy was not assessed in this EAP. However, some patients remained on treatment for up to a year, suggesting that they observed a benefit from treatment. Patients with CCA should undergo molecular testing to identify those who could benefit from targeted treatments such as pemigatinib.

Functional dichotomy between OX40 and 4-1BB in modulating effector CD8 T cell responses.

Lee, Seung-Woo,Park, Yunji,Song, Aihua,Cheroutre, Hilde,Kwon, Byoung S,Croft, Michael American Association of Immunologists 2006 Journal of Immunology Vol.177 No.7

<P>Members of the TNFR family are thought to deliver costimulatory signals to T cells and modulate their function and survival. In this study, we compare the role of two closely related TNFR family molecules, OX40 and 4-1BB, in generating effector CD8 T cells to Ag delivered by adenovirus. OX40 and 4-1BB were both induced on responding naive CD8 T cells, but 4-1BB exhibited faster and more sustained kinetics than OX40. OX40-deficient CD8 T cells initially expanded normally; however, their accumulation and survival at late times in the primary response was significantly impaired. In contrast, 4-1BB-deficient CD8 T cells displayed hyperresponsiveness, expanding more than wild-type cells. The 4-1BB-deficient CD8 T cells also showed enhanced maturation attributes, whereas OX40-deficient CD8 T cells had multiple defects in the expression of effector cell surface markers, the synthesis of cytokines, and in cytotoxic activity. These results suggest that, in contrast to current ideas, OX40 and 4-1BB can have a clear functional dichotomy in modulating effector CD8 T cell responses. OX40 can positively regulate effector function and late accumulation/survival, whereas 4-1BB can initially operate in a negative manner to limit primary CD8 responses.</P>

4-1BB Ligand Signaling to T Cells Limits T Cell Activation

Eun, So-Young,Lee, Seung-Woo,Xu, Yanfei,Croft, Michael American Association of Immunologists 2015 Journal of Immunology Vol. No.

<P>4-1BB ligand (4-1BBL) and its receptor, 4-1BB, are both induced on T cells after activation, but little is known about the role of 4-1BBL. In this study we show that 4-1BBL can transmit signals that limit T cell effector activity under tolerogenic conditions. Cross-linking 4-1BBL inhibited IL-2 production in vitro, primarily with suboptimal TCR stimulation. Furthermore, naive 4-1BBL–deficient OT-II transgenic T cells displayed a greater conversion to effector T cells in vivo when responding to soluble OVA peptide in wild-type hosts, whereas development of Foxp3<SUP>+</SUP> regulatory T cells was not altered. A greater number of effector T cells also differentiated from naive wild-type OT-II T cells when transferred into 4-1BB–deficient hosts, suggesting that APC-derived 4-1BB is likely to trigger 4-1BBL. Indeed, effector T cells that could not express 4-1BBL accumulated in larger numbers in vitro when stimulated with 4-1BB–expressing mesenteric lymph node dendritic cells. 4-1BBL was expressed on T cells when Ag presentation was limiting, and 4-1BBL was aberrantly expressed at very high levels on T cells that could not express 4-1BB. <I>Trans</I>-ligation, Ab capture, and endocytosis experiments additionally showed that T cell–intrinsic 4-1BB regulated internalization of membrane 4-1BBL, implying that the strong induction of 4-1BB on T cells may counteract the suppressive function of 4-1BBL by limiting its availability. These data suggest that 4-1BBL expressed on T cells can restrain effector T cell development, creating a more favorable regulatory T cell to effector cell balance under tolerogenic conditions, and this may be particularly active in mucosal barrier tissues where 4-1BB–expressing regulatory dendritic cells present Ag.</P>

Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells

Lee, Seung-Woo,Park, Yunji,So, Takanori,Kwon, Byoung S,Cheroutre, Hilde,Mittler, Robert S,Croft, Michael Nature Publishing Group 2008 Nature immunology Vol.9 No.8

The costimulatory molecule 4-1BB and its ligand 4-1BBL can control adaptive immunity, but here we show that their interaction also suppressed myelopoiesis. We found that 4-1BBL was expressed on hematopoietic stem cells, differentiating common myeloid progenitors and granulocyte-macrophage progenitors, and 4-1BB was inducible on activated myeloid progenitors. Steady-state numbers of granulocyte-macrophage progenitors, myeloid-lineage cells and mature dendritic cells were higher in 4-1BB- and 4-1BBL-deficient mice, indicative of a negative function, and we confirmed that result with bone marrow chimeras and in vitro, where the absence of interactions between 4-1BB and 4-1BBL led to enhanced differentiation into dendritic cell lineages. The regulatory activity was mediated by 4-1BBL, with binding by 4-1BB inhibiting differentiation of myeloid progenitors. Thus, 4-1BB and 4-1BBL have a previously unknown function in limiting myelopoiesis and the development of dendritic cells.

Combined CD137 (4-1BB) and adjuvant therapy generates a developing pool of peptide-specific CD8 memory T cells

Myers, Lara,Lee, Seung Woo,Rossi, Robert J.,Lefrancois, Leo,Kwon, Byoung S.,Mittler, Robert S.,Croft, Michael,Vella, Anthony T. Oxford University Press 2006 International immunology Vol.18 No.2

<P>In practice, vaccines should induce lasting and efficacious T cell immunity without promoting deleterious pathological consequences. To accomplish this goal we immunized mice with ovalbumin peptide, polyinosinic–polycytidylic and anti-CD137. Vaccinated mice retained a massive functional CD8 T cell memory pool in lymphoid and non-lymphoid tissues for >1 year. The memory T cells clonally expanded, produced substantial amounts of IFNγ, and responded vigorously to vesicular stomatitis virus infection. To understand how the vaccine might function, we showed that the antigen-specific T cells must bear CD137 in order for optimal priming to occur. Thus, anti-CD137 agonist mAb directly stimulated peptide-specific CD8 T cells and conditioned them to survive. In contrast, CD137-deficient CD8 T cells did not survive despite CD137 expression by antigen presenting cells. Taken together, the data indicate that CD137 and adjuvant combined therapy is an efficacious vaccine strategy for immunization with non-replicating inert antigen.</P>

Galectin-9 controls the therapeutic activity of 4-1BB–targeting antibodies

Madireddi, Shravan,Eun, So-Young,Lee, Seung-Woo,Nemč,ovič,ová,, Ivana,Mehta, Amit Kumar,Zajonc, Dirk M.,Nishi, Nozomu,Niki, Toshiro,Hirashima, Mitsuomi,Croft, Michael The Rockefeller University Press 2014 The Journal of experimental medicine Vol.211 No.7

<P>Biologics to TNF family receptors are prime candidates for therapy of immune disease. Whereas recent studies have highlighted a requirement for Fcγ receptors in enabling the activity of CD40, TRAILR, and GITR when engaged by antibodies, other TNFR molecules may be controlled by additional mechanisms. Antibodies to 4-1BB (CD137) are currently in clinical trials and can both augment immunity in cancer and promote regulatory T cells that inhibit autoimmune disease. We found that the action of agonist anti–4-1BB in suppressing autoimmune and allergic inflammation was completely dependent on Galectin-9 (Gal-9). Gal-9 directly bound to 4-1BB, in a site distinct from the binding site of antibodies and the natural ligand of 4-1BB, and Gal-9 facilitated 4-1BB aggregation, signaling, and functional activity in T cells, dendritic cells, and natural killer cells. Conservation of the Gal-9 interaction in humans has important implications for effective clinical targeting of 4-1BB and possibly other TNFR superfamily molecules.</P>