Fluorescence optical imaging: ready for prime time?

The novel technique of fluorescence optical imaging (FOI, Xiralite), which is approved in the European Union and the USA for clinical use, has been the object of studies since 2009. Indocyanine green-based FOI can demonstrate an impaired microcirculation caused by inflammation in both hands in one examination. Several studies have investigated FOI for detection of joint inflammation by comparing FOI to magnetic resonance imaging (MRI) and/or musculoskeletal ultrasound (MSUS). The results have shown a generally good agreement (>80%) between FOI and clinical examination, MRI and MSUS by power Doppler in inflammatory joint diseases. Moreover, characteristic enhancements in skin and nails are seen in PsA, which potentially can be useful in the diagnostic process of early undifferentiated arthritis. Furthermore, FOI has been investigated for the visualisation of a disturbed microcirculation in the hands and fingers of patients with systemic sclerosis (SSc), highlighting the potential of monitoring vascular changes in SSc and other vasculopathies. The available data indicate that it is time to consider FOI as a useful part of the imaging repertoire in rheumatology clinical practice, particularly where MSUS and MRI are not easily available.

Analysis of Clinical and Laboratory Findings of Idiopathic Sudden Sensorineural Hearing Loss

Idiopathic sudden sensorineural hearing loss (ISSNHL) is an emergency disease requiring immediate diagnosis and treatment. The incidence of ISSNHL in the Western countries’ population was estimated to 5–20 per 100,000 inhabitants. The etiology of ISSNHL remains unknown. Its pathogenesis is most often suggested to be due to a disturbed microcirculation and infection. Previous studies have reported that comorbidities, including hypertension, diabetes mellitus (DM), and hyperfibrinogenemia are risk factors of ISSNHL. This study aimed at investigating the clinical characteristics, laboratory parameters and comorbidities of patients with ISSNHL. Our study suggests that the annual incidence of ISSNHL in China mainland is 19 per 100 000. The clinical characteristics and prevalence of comorbidities of ISSNHL patients are different according to age distribution and hearing results. Moreover, the patients with vertigo, hypertension, DM and high TG suffered more often from severe hearing loss compared with the counterparts. This indicates that the cardiovascular and metabolic diseases (hypertension and hyperlipidemia) appeared to be closely associated with the occurrence and severity of ISSNHL.

New treatment options for thrombotic thrombocytopenic purpura

SummaryThe thrombotic-thrombocytopenic purpura (TTP) is an acute, life-threatening disease, characterised by enhanced platelet aggregation, disturbed microcirculation and organ dysfunction. With the currently available treatment (plasma exchange, infusions, corticosteroids) mortality ist still as high as 10–15 %. Recent, pathophysiology-based developments may improve the outcome. The most promising candidates for future treatment of TTP are: rituximab for termination of the autoimmune process, caplacizumab for prevention of platelet-VWF-interaction, and recombinant ADAMTS13 for replacement of the inhibited or missing enzyme.

Treatment of thrombotic microangiopathy with a focus on new treatment options

SummaryThe thrombotic microangiopathies (TMA) are a heterogeneous group of disorders, characterized by microangiopathic haemolytic anaemia with red cell fragmentation, thrombocytopenia and signs of organ dysfunction due to disturbed microcirculation. Current laboratory methods can be used to better distinguish some of these entities. Organ dysfunction can be severe and life-threatening, and immediate start of sufficient therapy is necessary to avoid permanent damage or death. The therapeutic options, however, are often limited to symptomatic measures, and are not standardized or based on high scientific evidence. During the preceding years, not only considerable progress has been made in better diagnosis of TMA, but also new therapeutic strategies have been established. Initial treatment still is based on plasma exchange and symptomatic measures to protect organ function. New concepts (immunosuppression, targeted anti-von Willebrand factor or anti-complement therapy, replacement with recombinant enzymes) are discussed in this article.

ICAM-1 Upregulation in Ethanol-Induced Fatty Murine Livers Promotes Injury and Sinusoidal Leukocyte Adherence after Transplantation

Background. Transplantation of ethanol-induced steatotic livers causes increased graft injury. We hypothesized that upregulation of hepatic ICAM-1 after ethanol produces increased leukocyte adherence, resulting in increased generation of reactive oxygen species (ROS) and injury after liver transplantation (LT). Methods. C57BL/6 wildtype (WT) and ICAM-1 knockout (KO) mice were gavaged with ethanol (6 g/kg) or water. LT was then performed into WT recipients. Necrosis and apoptosis, 4-hydroxynonenal (4-HNE) immunostaining, and sinusoidal leukocyte movement by intravital microscopy were assessed. Results. Ethanol gavage of WT mice increased hepatic triglycerides 10-fold compared to water treatment (P<0.05). ICAM-1 also increased, but ALT was normal. At 8 h after LT of WT grafts, ALT increased 2-fold more with ethanol than water treatment (P<0.05). Compared to ethanol-treated WT grafts, ALT from ethanol-treated KO grafts was 78% less (P<0.05). Apoptosis also decreased by 75% (P<0.05), and 4-HNE staining after LT was also decreased in ethanol-treated KO grafts compared to WT. Intravital microscopy demonstrated a 2-fold decrease in leukocyte adhesion in KO grafts compared to WT grafts. Conclusions. Increased ICAM-1 expression in ethanol-treated fatty livers predisposes to leukocyte adherence after LT, which leads to a disturbed microcirculation, oxidative stress and graft injury.

Treatment of invasive streptococcal infection with a peptide derived from human high-molecular weight kininogen

Sepsis and septic shock remain an important medical problem, emphasizing the need to identify novel therapeutic opportunities. Hypovolemic hypotension, coagulation dysfunction, disturbed microcirculation, and multiorgan failure resulting from vascular leakage are often observed in these severe conditions. In the present study, we find that HKH20, a peptide derived from human high molecular weight kininogen (HK), down-regulates inflammatory reactions caused by Streptococcus pyogenes in a mouse model of sepsis. HK is a component of the pro-inflammatory and pro-coagulant contact system. Activation of the contact system in the bloodstream by S pyogenes leads to massive tissue damage in the lungs of the infected mice, which eventually results in the death of the animals. HKH20 inhibits activation of the contact system and protects mice with invasive S pyogenes infection from lung damage. In combination with clindamycin treatment, the peptide also significantly prolongs the survival of infected mice.