Activation of the IL-1ß/KLF2/HSPH1 pathway promotes STAT3 phosphorylation in alveolar macrophages during LPS-induced acute lung injury.

Acute lung injury (ALI) is a lethal disease with diffuse lung inflammation, in which JAK/STAT3 signaling has been well recognized for its role in initiating and amplifying inflammatory processes. However, the mechanism for the enhancement and maintenance of signal transducer and activator of transcription 3 (STAT3) activation has not yet been clearly demonstrated in ALI. In the present work, we established a lipopolysaccharide (LPS)-induced ALI rat model through intratracheal instillation and isolated the alveolar macrophages (AMs) from the rats in the model. We demonstrated that the expression of Kruppel-like factor 2 (KLF2) significantly decreased in the AMs from LPS-induced ALI rats (LPS-AMs) as compared with the AMs from control rats (NC-AMs). Overexpressing KLF2 in LPS-AMs inhibited the phosphorylation of STAT3 and reduced the levels of STAT3 target genes, including matrix metalloproteinase (MMP)-2/9 (MMP-2/9). Further investigation indicated that KLF2 trans-inhibited heat shock protein H1 (HSPH1), which interacted with STAT3 and enhanced its phosphorylation. As a crucial inflammatory mediator in ALI, interleukin-1ß (IL-1ß) induced the down-regulation of KLF2 in LPS-AMs, as interrupting IL-1ß signaling in LPS-AMs by antibody neutralization or IL1R1 knockdown rescued the expression of KLF2. Consistently, stimulating NC-AMs with IL-1ß decreased KLF2 and increased HSPH1, while overexpression of KLF2 suppressed IL-1ß-induced HSPH1. Additionally, in vivo studies showed that treatment with an IL-1ß antibody or HSPH1 inhibitor alleviated lung injury in ALI rats, as well as decreased the levels of p-STAT3 and MMP-2/9. In conclusion, activation of the IL-1ß/KLF2/HSPH1 pathway facilitated STAT3 phosphorylation in AMs, which exacerbated pulmonary inflammation in ALI.

Pyoderma gangrenosum: a review of clinical features and outcomes of 23 cases requiring inpatient management.

Pyoderma gangrenosum (PG) is a rare dermatological disorder characterised by the rapid progression of a painful, necrolytic ulcer. This study retrospectively identified patients who were admitted and treated for PG during a 10-year period (2003-2013). Twenty-three patients were included in this study, 16 women and seven men. The mean age at initial admission was 62.8 years (range 30 to 89 years). Lesions were localised to lower limb in 13 patients, peristomal region in four, breast in three, and upper limb in one, and two patients had PG at multiple sites. The variants of PG noted were ulcerative (18), bullous (2), vegetative (2), and pustular (1). Associated systemic diseases were observed in 11 patients (47.8%). Systemic therapies were initiated in 21 patients while two patients received topical treatments. The mean length of hospital stay was 47 days (range 5 to 243 days) and five patients died during their admissions. Seven patients required readmissions for exacerbations of their PG. Our study showed that patients admitted for treatment of PG had high morbidity and mortality. This study also highlights the importance of early and aggressive treatment of patients admitted with PG as well as treating associated systemic diseases and wound infections.

A 10 year retrospective study of surgical outcomes of adult intracranial pilocytic astrocytoma.

Pilocytic astrocytomas (PA) are benign neoplasms commonly located in the cerebellum with a peak incidence in the first two decades of life. PA occurrence in adults is rare and very little information is available in the literature about tumour characteristics in this population. This study retrospectively identified 20 adults with PA. The characteristics of the tumour, treatment modalities and patient outcomes are discussed, as well as identifying factors that may be associated with worse prognosis. The mean age at diagnosis was 27 years. The majority of PA were located in the posterior fossa. Other tumour locations included the cerebral hemispheres, brainstem, tectal plate and optochiasmatic region (optic chiasm, hypothalamus and third ventricle). All patients in this study underwent surgery, two received adjuvant chemotherapy and one received adjuvant radiotherapy. Tumour recurrence occurred in six patients and two eventually died from the disease. When achieved, complete tumour resection was found to be curative. Tumour location affects extent of surgical resection; tumours in inaccessible locations were associated with higher rates of recurrence. Overall survival and progression free survival rates were 87% and 60% respectively. The degree of surgical resection and tumour location were found to affect prognosis. Unfavourable outcomes were observed in these adults with PA compared to those expected for a younger population, suggesting a possible association between age and outcome.

A challenging diagnosis: case report of extensive pyoderma gangrenosum at multiple sites.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare dermatological condition characterized by the rapid progression of a painful, necrolytic ulcer with an irregular, undermined border and commonly affects the lower extremities, mainly in the pretibial area. The diagnosis of PG is not easy. Due to lack of diagnostic laboratory test and histopathological findings indicative of PG, it is often misdiagnosed as an infection. This results in delayed or inappropriate treatment of the condition, which leads to devastating consequences such as limb amputation and death. MAIN OBSERVATIONS: We report a rare case of a 51-year-old female who was initially diagnosed as having infected ulcers and underwent serial debridements, which resulted in extensive PG at three different sites (abdominal, left thigh, and sacral). CONCLUSION: This case highlights the challenges in diagnosing PG, emphasizes the key clinical features to aid diagnosis, and the clinical consequences of delayed or misdiagnosis of this condition.

Tenosynovial giant cell tumour of brachial plexus.

Tenosynovial giant cell tumours (TGT) are benign tumours that arise in the synovial lining of joints, tendon sheaths and bursae. Tumours arising from the vertebral column are extremely rare, with few cases reported. In this article, we describe an unusual case of an extra-articular TGT of the brachial plexus, arising from the synovium of the vertebral facet joint. To our knowledge and after a review of the literature, this is the first patient with a TGT involving the brachial plexus. The clinical, radiological and histological features of this tumour are described together with a brief discussion of management options.