Successful Treatment of Spondylodiscitis and Infectious Sacroiliitis due to Listeria monocytogenes using Meropenem as Salvage Therapy

Infectious sacroiliitis is a rare disease that can occur in conjunction with other osteoarticular infections. Furthermore, it is very unusual for Listeria monocytogenes to be identified in an osteoarticular infection, with spondylodiscitis being the most frequent such infection. We report a case of spondylodiscitis with infectious sacroiliitis due to infection with L. monocytogenes treated successfully with meropenem as salvage therapy

An Atypical Case of Vasculitis: When ‘Occult’ 18FDG-PET Scan Findings Create a Classification Dilemma

We describe a 66-year old patient with a recurrent ulcer on her right ankle. Biopsy revealed medium-vessel vasculitis consistent with cutaneous polyarteritis nodosa. There were no signs or symptoms suggestive of systemic vasculitis, but a 18FDG-PET scan showed areas of increased uptake around the large arteries and the pelvic and shoulder girdles. These findings suggested polymyalgia rheumatica in the setting of large-vessel vasculitis. This case thus supports the statement from the Chapel-Hill consensus conference that classification of systemic vasculitis by vessel size is based on the vessels predominantly involved, but vessels of other sizes may also be affected

Hydroxychloroquine in a G6PD-Deficient Patient with COVID-19 Complicated by Haemolytic Anaemia: Culprit or Innocent Bystander?

Hydroxychloroquine has been used worldwide as a first-line treatment for patients hospitalized with COVID-19. Little is known about COVID-19 and its effects on patients with congenital red blood cell disorders. We report a case of haemolytic anaemia in a 32-year-old patient and a fortuitous highlighting of G6PD deficiency. We reviewed the literature to assess the risk of hydroxychloroquine use in this context

Heparin-Binding-Hemagglutinin-Induced IFN-γ Release as a Diagnostic Tool for Latent Tuberculosis

BACKGROUND: The detection of latent tuberculosis infection (LTBI) is a major component of tuberculosis (TB) control strategies. In addition to the tuberculosis skin test (TST), novel blood tests, based on in vitro release of IFN-gamma in response to Mycobacterium tuberculosis-specific antigens ESAT-6 and CFP-10 (IGRAs), are used for TB diagnosis. However, neither IGRAs nor the TST can separate acute TB from LTBI, and there is concern that responses in IGRAs may decline with time after infection. We have therefore evaluated the potential of the novel antigen heparin-binding hemagglutinin (HBHA) for in vitro detection of LTBI. METHODOLOGY AND PRINCIPAL FINDINGS: HBHA was compared to purified protein derivative (PPD) and ESAT-6 in IGRAs on lymphocytes drawn from 205 individuals living in Belgium, a country with low TB prevalence, where BCG vaccination is not routinely used. Among these subjects, 89 had active TB, 65 had LTBI, based on well-standardized TST reactions and 51 were negative controls. HBHA was significantly more sensitive than ESAT-6 and more specific than PPD for the detection of LTBI. PPD-based tests yielded 90.00% sensitivity and 70.00% specificity for the detection of LTBI, whereas the sensitivity and specificity for the ESAT-6-based tests were 40.74% and 90.91%, and those for the HBHA-based tests were 92.06% and 93.88%, respectively. The QuantiFERON-TB Gold In-Tube (QFT-IT) test applied on 20 LTBI subjects yielded 50% sensitivity. The HBHA IGRA was not influenced by prior BCG vaccination, and, in contrast to the QFT-IT test, remote (>2 years) infections were detected as well as recent (<2 years) infections by the HBHA-specific test. CONCLUSIONS: The use of ESAT-6- and CFP-10-based IGRAs may underestimate the incidence of LTBI, whereas the use of HBHA may combine the operational advantages of IGRAs with high sensitivity and specificity for latent infection.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Sudden Development of Subcutaneous Nodules Shortly after Radioiodine Treatment for Thyroid Cancer Caused by Self-Limiting Sarcoidosis

Background: Sarcoidosis is a multisystemic disease producing non-caseating granulomas. The aetiology and pathogenesis are unknown. We herewith report an atypical case of cutaneous sarcoidosis.Case presentation: A 50-year-old female presented with an onset of multiple subcutaneous nodules on her 4 limbs. These nodules appeared concomitantly with the initiation of radioactive iodine therapy for papillary thyroid cancer. These nodules were not obvious on inspection of the skin, but easily felt on palpation.The biopsy of the subcutaneous nodules revealed hypodermic non-caseating granulomas consistent with sarcoidosis. The patient underwent an 18F-fluorodeoxyglucose positron emission tomography (PET) scan study that revealed, besides the subcutaneous nodules, multiple hypermetabolic mediastinal lymphadenopathies and cervical adenopathies. Biopsy of the mediastinal lymphadenopathy showed neither granulomas nor neoplastic cells. Cervical biopsy revealed neoplastic cells of thyroid origin. Laboratory tests were normal. Bronchoalveolar lavage showed a normal CD4/CD8 T-cell ratio. A diagnosis of cutaneous sarcoidosis was established, as well as a recurrence of the cancerous disease. The subcutaneous nodules regressed spontaneously in the absence of any treatment.Discussion and conclusion: Sarcoidosis is a multisystemic disease of unknown origin. This case illustrates an uncommon occurrence of sarcoidosis, triggered by radioactive iodine therapy. Radioiodine may lead to immunological changes, especially affecting the Th1/Th2 ratio, which may promote the emergence of sarcoidosis in genetically predisposed patients. There is still much to discover to fully understand the pathogenesis of sarcoidosis

Effector functions of heparin-binding hemagglutinin-specific CD8+ T lymphocytes in latent human tuberculosis.

BACKGROUND: Most individuals infected with Mycobacterium tuberculosis do not develop tuberculosis (TB) and can be regarded as being protected by an appropriate immune response to the infection. The characterization of the immune responses of individuals with latent TB may thus be helpful in the definition of correlates of protection and the development of new vaccine strategies. The highly protective antigen heparin-binding hemagglutinin (HBHA) induces strong interferon (IFN)- gamma responses during latent, but not active, TB. Because of the recently recognized importance of CD8(+) T lymphocytes in anti-TB immunity, we characterized the CD8(+) T lymphocyte responses to HBHA in subjects with latent TB. RESULTS: HBHA-specific CD8(+) T lymphocytes expressed memory cell markers and synthesized HBHA-specific IFN- gamma .They also restricted mycobacterial growth and expressed cytotoxicity by a granule-dependent mechanism. This activity was associated with the intracellular expression of HBHA-induced perforin. Surprisingly, the perforin-producing CD8(+) T lymphocytes were distinct from the IFN- gamma -producing CD8(+) T lymphocytes. CONCLUSION: During latent TB, the HBHA-specific CD8(+) T lymphocyte population expresses all 3 effector functions associated with CD8(+) T lymphocyte-mediated protective immune mechanisms, which supports the notion that HBHA may be protective in humans and suggests that markers of HBHA-specific CD8(+) T lymphocyte responses may be useful in the monitoring of protection.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Heparin-binding hemagglutinin, from an extrapulmonary dissemination factor to a powerful diagnostic and protective antigen against tuberculosis.

Interactions of Mycobacterium tuberculosis with macrophages have long been recognized to be crucial to the pathogenesis of tuberculosis. The role of non-phagocytic cells is less well known. We have discovered a M. tuberculosis surface protein that interacts specifically with non-phagocytic cells, expresses hemagglutination activity and binds to sulfated glycoconjugates. It is therefore called heparin-binding hemagglutinin (HBHA). HBHA-deficient M. tuberculosis mutant strains are significantly impaired in their ability to disseminate from the lungs to other tissues, suggesting that the interaction with non-phagocytic cells, such as pulmonary epithelial cells, may play an important role in the extrapulmonary dissemination of the tubercle bacillus, one of the key steps that may lead to latency. Latently infected human individuals mount a strong T cell response to HBHA, whereas patients with active disease do not, suggesting that HBHA is a good marker for the immunodiagnosis of latent tuberculosis, and that HBHA-specific Th1 responses may contribute to protective immunity against active tuberculosis. Strong HBHA-mediated immuno-protection was shown in mouse challenge models. HBHA is a methylated protein and its antigenicity in latently infected subjects, as well as its protective immunogenicity strongly depends on the methylation pattern of HBHA. In both mice and man, the HBHA-specific IFN-gamma was produced by both the CD4(+) and the CD8(+) T cells. Furthermore, the HBHA-specific CD8(+) T cells expressed bactericidal and cytotoxic activities to mycobacteria-infected macrophages. This latter activity is most likely perforin mediated. Together, these observations strongly support the potential of methylated HBHA as an important component in future, acellular vaccines against tuberculosis.Journal ArticleResearch Support, Non-U.S. Gov'tReviewinfo:eu-repo/semantics/publishe

Fibrose pulmonaire idiopathique

SCOPUS: ar.jinfo:eu-repo/semantics/publishe