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JCI Insight Oct 2020Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease characterized by chronic abscess formation and development of multiple draining sinus...
Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease characterized by chronic abscess formation and development of multiple draining sinus tracts in the groin, axillae, and perineum. Using proteomic and transcriptomic approaches, we characterized the inflammatory responses in HS in depth, revealing immune responses centered on IFN-γ, IL-36, and TNF, with lesser contribution from IL-17A. We further identified B cells and plasma cells, with associated increases in immunoglobulin production and complement activation, as pivotal players in HS pathogenesis, with Bruton's tyrosine kinase (BTK) and spleen tyrosine kinase (SYK) pathway activation as a central signal transduction network in HS. These data provide preclinical evidence to accelerate the path toward clinical trials targeting BTK and SYK signaling in moderate-to-severe HS.
Topics: Agammaglobulinaemia Tyrosine Kinase; B-Lymphocytes; Biomarkers; Case-Control Studies; Gene Expression Regulation; Gene Regulatory Networks; Hidradenitis Suppurativa; Humans; Plasma Cells; Proteome; Signal Transduction; Single-Cell Analysis; Syk Kinase; Transcriptome
PubMed: 32853177
DOI: 10.1172/jci.insight.139930 -
Acta Gastro-enterologica Belgica 2019Splenic abscess is a rare but potentially fatal entity, occurring mainly in patients with underlying risk factors. Mortality of the disease depends on the time of... (Review)
Review
Splenic abscess is a rare but potentially fatal entity, occurring mainly in patients with underlying risk factors. Mortality of the disease depends on the time of diagnosis and treatment. Due to low sensitivity and specificity of clinical symptoms and laboratory markers, imaging plays the vital role in the diagnostic work-up. The aim of this article is to give a concise overview of the methods of splenic abscess diagnosis.
Topics: Abscess; Bacterial Infections; Humans; Intraabdominal Infections; Risk Factors; Splenic Diseases; Time Factors
PubMed: 31566331
DOI: No ID Found -
Cureus Aug 2021Infective endocarditis (IE) secondary to and streptococcus species comprises the majority of cases in literature with Gram negative bacterial insults occurring...
Infective endocarditis (IE) secondary to and streptococcus species comprises the majority of cases in literature with Gram negative bacterial insults occurring infrequently. is a Gram negative bacillus which is classified as motile, non-lactose fermenting, and a facultative anerobe. The presumed risk factor for the development of IE is intravenous drug use (IVDU). We report two cases of IE causes by : first case describes IE of tricuspid and aortic valve requiring surgical intervention further complicated by epidural abscess. The second case was associated with renal and splenic infarct. These cases highlight the severity and complicated nature of IE. Given IE has been infrequently described in the literature, we believe that our cases are worth reporting to contribute to the present incidence and management of IE.
PubMed: 34567887
DOI: 10.7759/cureus.17346 -
BMJ Case Reports Oct 2020A 43-year-old woman with Crohn's disease was admitted to the hospital with weight loss and 1 week of fever, abdominal pain and diarrhoea. At presentation, the patient...
A 43-year-old woman with Crohn's disease was admitted to the hospital with weight loss and 1 week of fever, abdominal pain and diarrhoea. At presentation, the patient was not on steroids or other immunosuppressive agents. Cross-sectional imaging of the abdomen revealed active colitis and multiple splenic and hepatic abscesses. All culture data were negative, including aspiration of purulent material from the spleen. Despite weeks of intravenous antibiotics, daily fever and abdominal pain persisted, the intra-abdominal abscesses grew, and she developed pleuritic chest pain and consolidations of the right lung. The patient was ultimately diagnosed with aseptic abscess syndrome, a rare sequelae of inflammatory bowel disease. All antimicrobials were discontinued and she was treated with high-dose intravenous steroids, resulting in rapid clinical improvement. She was transitioned to infliximab and azathioprine as an outpatient and repeat imaging demonstrated complete resolution of the deep abscesses that had involved her spleen, liver and lungs.
Topics: Abdominal Abscess; Adult; Anti-Bacterial Agents; Crohn Disease; Diagnosis, Differential; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Syndrome; Tomography, X-Ray Computed
PubMed: 33122231
DOI: 10.1136/bcr-2020-236437 -
The Lancet. Microbe Dec 2021Hypervirulent (hv) strains of capsule type K1 and K2 cause invasive infections associated with hepatic abscesses, which can be difficult to treat and are frequently...
BACKGROUND
Hypervirulent (hv) strains of capsule type K1 and K2 cause invasive infections associated with hepatic abscesses, which can be difficult to treat and are frequently associated with relapsing infections. Other strains (non-hv), including lineages that have acquired carbapenem resistance, do not manifest this pathology. In this work we aimed to test the hypothesis that within-macrophage replication is a key mechanism underpinning abscess formation in hv infections.
METHODS
In this exploratory investigation, to study the pathophysiology of abscess formation, mice were intravenously infected with 10 colony forming units (CFU) of either hv isolates (six strains) or non-hv isolates (seven strains). Intracellular bacterial replication and neutrophil influx in liver and spleen was quantified by fluorescence microscopy of sliced cryopreserved organs of mice collected 30 min, 6 h, and 24 h after infection with the aim to provide data of bacterial association to Kupffer cells in the liver and to the different tissue macrophages in the spleen. Microbiological and microscopy analysis of an ex-vivo model of pig liver and spleen infection were used to confirm within-macrophage replication. Pig organs were perfused with heparinised, autologous pig's blood and injected with 6·5 × 10 CFU of hv K2 sequence type 25 strain GMR151. Blood and tissue biopsies collected before infection and 30 min, 1 h, 2 h, 3 h, 4 h, and 5 h after infection were used to measure bacterial counts and to identify the subcellular localisation of bacteria by immunohistochemistry analysis.
FINDINGS
We show that hv resisted phagocyte-mediated clearance and replicated in mouse liver macrophages to form clusters 6 h after infection, with a mean of 7·0 bacteria per Kupffer cell (SD 6·2); however, non-hv were efficiently cleared (mean 1·5 bacteria per cell [SD 1·1]). Hv infection promoted neutrophil recruitment to sites of infection, which in the liver resulted in histopathological signs of abscess formation as early as 24 h post-infection. Experiments in pig organs which share a high functional and anatomical resemblance to human organs, provided strong evidence for the propensity of hv to replicate within the hepatic macrophages.
INTERPRETATION
These findings show subversion of innate immune processes in the liver by and resistance to Kupffer cell mediated clearance as an explanation for the propensity of hv strains to cause hepatic abscesses.
FUNDING
University of Oxford and a Royal Society Wolfson grant funded biosafety facility.
Topics: Animals; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess; Macrophages; Mice; Perfusion; Swine; Virulence
PubMed: 34901898
DOI: 10.1016/S2666-5247(21)00195-6 -
Annals of Translational Medicine Jul 2021The spleen is a commonly injured organ in blunt abdominal trauma. Splenic preservation, however, is important for immune function and prevention of overwhelming... (Review)
Review
The spleen is a commonly injured organ in blunt abdominal trauma. Splenic preservation, however, is important for immune function and prevention of overwhelming infection from encapsulated organisms. Splenic artery embolization (SAE) for high-grade splenic injury has, therefore, increasingly become an important component of non-operative management (NOM). SAE decreases the blood pressure to the spleen to allow healing, but preserves splenic perfusion via robust collateral pathways. SAE can be performed proximally in the main splenic artery, more distally in specific injured branches, or a combination of both proximal and distal embolization. No definitive evidence from available data supports benefits of one strategy over the other. Particles, coils and vascular plugs are the major embolic agents used. Incorporation of SAE in the management of blunt splenic trauma has significantly improved success rates of NOM and spleen salvage. Failure rates generally increase with higher injury severity grades; however, current management results in overall spleen salvage rates of over 85%. Complication rates are low, and primarily consist of rebleeding, parenchymal infarction or abscess. Splenic immune function is felt to be preserved after embolization with no guidelines for prophylactic vaccination against encapsulated bacteria; however, a complete understanding of post-embolization immune changes remains an area in need of further investigation. This review describes the history of SAE from its inception to its current role and indications in the management of splenic trauma. The endovascular approach, technical details, and outcomes are described with relevant examples. SAE is has become an important part of a multidisciplinary strategy for management of complex trauma patients.
PubMed: 34430635
DOI: 10.21037/atm-20-4381