Use of a Novel Catheter, the MOT-C, for Selective Angiography of the Internal Mammary Artery From Ipsilateral Radial Access.

OBJECTIVE: We describe a novel catheter, the MOT-C (Merit Medical Systems), for selective diagnostic angiography of the internal mammary artery from radial access. METHODS: We analyzed the pattern of radial versus femoral access for bypass angiography at our institution between 2012 and 2020. We also examined the difference in contrast volume and fluoroscopy time between radial and femoral access and between MOT-C and traditional internal mammary artery (IMA) catheter for bypass angiography. RESULTS: Since the introduction of MOT-C catheter to our laboratory in 2016, there has been a 1.5-fold increase in the use of radial access for bypass angiography. No significant difference in contrast volume or fluoroscopy time was noted between radial and femoral access for bypass angiography. The MOT-C catheter was successfully used in 46% of all cases and 77% of all radial cases between 2016 and 2020 to selectively engage the IMA. When compared with the traditional IMA catheter, no statistically significant difference was noted in contrast volume or fluoroscopy time with the use of MOT-C for bypass angiography, although there was a trend toward lower contrast use. Furthermore, no catheter-related complications occurred. CONCLUSIONS: The MOT-C facilitates improved engagement of IMA grafts with minimal manipulation and allows for high-quality diagnostic angiograms with a potential decrease in contrast volume compared with the more traditionally used IMA catheter.

A retrospective cohort study of patients treated with anti-tuberculous therapy for presumed ocular tuberculosis.

BACKGROUND: Uveitis involving the posterior segment is a significant and potentially blinding condition. The diagnosis and treatment of patients with uveitis associated with tuberculosis remains controversial, and commonly, patients are systemically well. Use of the interferon-gamma release assays has added to the controversy, as the significance of a positive test may be uncertain. We aim to report the outcomes of anti-tuberculous treatment in a cohort of patients treated in Birmingham, for presumed "ocular tuberculosis", based on clinical findings, systemic assessment and specific testing for tuberculosis. RESULTS: We found that in our cohort of 41 patients treated between 2010 and 2014, the majority achieved disease-free remission, even in cases where anti-tuberculous treatment was delayed. CONCLUSIONS: Despite controversy, this study strongly supports the use of anti-tuberculous therapy in such patients and highlights the need for formal prospective trials and treatment protocols.

Preservation of a critical epitope core region is associated with the high degree of flaviviral cross-reactivity exhibited by a dengue-specific CD4+ T cell clone.

Dengue is a member of the Flaviviridae, a large group of related viruses some of which co-circulate in certain regions (e.g. dengue and Yellow fever in South America). Immune responses cross-reactive between different dengue serotypes are important in the pathogenesis of dengue disease but it is not known whether previous infection with one flavivirus might affect the clinical course of subsequent infections with other members of the family. CD4+ T cells have been shown to be important in the production of cytokines in response to dengue infection and can demonstrate significant epitope cross-reactivity. Here, we describe the generation and characterisation of CD4+ T cell clones from a patient experiencing acute dengue infection. These clones were DRB1*15+ and recognised epitope variants not only within other dengue viruses but certain other flaviviruses. This cross-reactivity was dependent upon the presence of a five-amino acid core region, consistent with structural observations of class II MHC binding to TCR demonstrating that only a subset of residues within an epitope bound to a class II molecule are "read out" by the TCR. This capacity of CD4+ T cell clones to recognise a given epitope despite considerable variation between viruses may be of pathological significance, particularly in regions where related viruses co-circulate.

High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic T-cells during the course of secondary dengue virus infection.

BACKGROUND: Dengue is one of the most important human diseases transmitted by an arthropod vector and the incidence of dengue virus infection has been increasing - over half the world's population now live in areas at risk of infection. Most infections are asymptomatic, but a subset of patients experience a potentially fatal shock syndrome characterised by plasma leakage. Severe forms of dengue are epidemiologically associated with repeated infection by more than one of the four dengue virus serotypes. Generally attributed to the phenomenon of antibody-dependent enhancement, recent observations indicate that T-cells may also influence disease phenotype. METHODS AND FINDINGS: Virus-specific cytotoxic T lymphocytes (CTL) showing high level cross reactivity between dengue serotypes could be expanded from blood samples taken during the acute phase of secondary dengue infection. These could not be detected in convalescence when only CTL populations demonstrating significant serotype specificity were identified. Dengue cross-reactive CTL clones derived from these patients were of higher avidity than serotype-specific clones and produced much higher levels of both type 1 and certain type 2 cytokines, many previously implicated in dengue pathogenesis. CONCLUSION: Dengue serotype cross-reactive CTL clones showing high avidity for antigen produce higher levels of inflammatory cytokines than serotype-specific clones. That such cells cannot be expanded from convalescent samples suggests that they may be depleted, perhaps as a consequence of activation-induced cell death. Such high avidity cross-reactive memory CTL may produce inflammatory cytokines during the course of secondary infection, contributing to the pathogenesis of vascular leak. These cells appear to be subsequently deleted leaving a more serotype-specific memory CTL pool. Further studies are needed to relate these cellular observations to disease phenotype in a large group of patients. If confirmed they have significant implications for understanding the role of virus-specific CTL in pathogenesis of dengue disease.

Increased frequencies of CD4+ CD25(high) regulatory T cells in acute dengue infection.

Dengue virus infection is an increasingly important tropical disease, causing 100 million cases each year. Symptoms range from mild febrile illness to severe hemorrhagic fever. The pathogenesis is incompletely understood, but immunopathology is thought to play a part, with antibody-dependent enhancement and massive immune activation of T cells and monocytes/macrophages leading to a disproportionate production of proinflammatory cytokines. We sought to investigate whether a defective population of regulatory T cells (T reg cells) could be contributing to immunopathology in severe dengue disease. CD4(+)CD25(high)FoxP3(+) T reg cells of patients with acute dengue infection of different severities showed a conventional phenotype. Unexpectedly, their capacity to suppress T cell proliferation and to secrete interleukin-10 was not altered. Moreover, T reg cells suppressed the production of vasoactive cytokines after dengue-specific stimulation. Furthermore, T reg cell frequencies and also T reg cell/effector T cell ratios were increased in patients with acute infection. A strong indication that a relative rise of T reg cell/effector T cell ratios is beneficial for disease outcome comes from patients with mild disease in which this ratio is significantly increased (P < 0.0001) in contrast to severe cases (P = 0.2145). We conclude that although T reg cells expand and function normally in acute dengue infection, their relative frequencies are insufficient to control the immunopathology of severe disease.

Increased expression of inhibitor of apoptosis proteins in atherosclerotic plaques of symptomatic patients with carotid stenosis.

Vascular remodeling and atheromatous lesion formation are determined in part by the balance between apoptosis and survival of vascular smooth muscle cells (VSMCs). In the chronic stages, apoptosis of VSMCs in the atherosclerotic plaques contributes to the weakening and potential rupture of the plaque causing pathologies such as acute coronary syndrome. The higher incidence of apoptosis in the plaques of symptomatic than in asymptomatic patients has been demonstrated, but the expression of survival proteins, including the inhibitor of apoptosis proteins (IAPs), has not been thoroughly examined. The aim of this study was to investigate the immunohistochemical expression of cellular inhibitor of apoptosis protein-2 (cIAP2), x-linked inhibitor of apoptosis protein (XIAP), and survivin in normal carotid arteries, and carotid endarterectomy specimens of symptomatic and asymptomatic patients with carotid stenosis. The results demonstrated stronger immunopositivity to smooth muscle myosin heavy chain antigen (SM-MHC) (sm2), proliferating cell nuclear antigen (PCNA), and p50 subunit of NF-kappabeta in the asymptomatic plaques than in symptomatic plaques. Furthermore, there was higher expression of cIAP2, XIAP, and survivin in the symptomatic than in the asymptomatic plaques and this paralleled caspase-3 expression. The increased expression of IAPs in symptomatic plaques could be due to endogenous defense mechanism to protect against the pro-apoptotic effect of the inflammatory stimuli that are released in the plaques. This could be involved in the stabilization of symptomatic atheromatous plaques and may prove a potential therapeutic target.

The duPont kyphosis brace for the treatment of adolescent Scheuermann kyphosis.

The purpose of this study was to evaluate the effectiveness of a newly designed brace in the treatment of adolescent Scheuermann thoracic kyphosis. Twenty-two children who met the roentgenographic criteria of Scheuermann kyphosis and were compliant with treatment were followed until skeletal maturity. Sixteen patients (73%) showed nonprogression of their kyphosis (nine patients demonstrated an improvement, seven patients remained unchanged), and had a mean improvement of 9 degrees (64 degrees to 55 degrees). Six patients (27%) demonstrated progression of the kyphosis and had a mean increase in their kyphosis of 9 degrees (59 degrees to 68 degrees). One patient underwent posterior spinal fusion for progressive thoracic kyphosis despite bracing. It was recommended that this brace be worn until skeletal maturity; in this study this time period was determined to be at least 16 months to induce improvement or halt progression of this disease. Flexible curves are a positive predictor of a successful outcome of bracing with the kyphosis brace. These results are comparable to previous reports in the literature describing the effectiveness of the modified Milwaukee brace in the treatment of Scheuermann thoracic kyphosis prior to skeletal maturity, and the kyphosis brace has the advantage of concealability under normal attire.