Actinomyces canaliculitis presents with epiphora, chronic purulent conjunctivitis, a palpably thickened canaliculus, and yellow punctual discharge. In suspect cases canuliculotomy and curettage should be performed, although canalicular reconstruction is generally unnecessary. Culture of discharge and concretions using PD Plus/F blood culture medium gave improved results over accepted norms. Fixation of smeared concretions on a slide in alcohol is simple and is diagnostic of the disease. We recommend long-term systemic penicillin treatment in Actinomyces canaliculitis.

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Although present in normal cells, epidermal growth factor receptor (EGFR) is overexpressed in a variety of tumors and has been associated with decreased survival. Because activated fibroblasts are considered key effectors in fibrosis and because metastatic and fibrotic processes were shown to share similar signaling pathways, we investigated the contribution of EGFR signaling to idiopathic pulmonary fibrosis (IPF) progression in lung fibroblasts derived from patients with IPF (IPF-HLF). EGFR expression and EGFR-related signaling were evaluated by Western blot and immunohistochemistry. Supernatants (SN) from cultured IPF-HLF and N-HLF were added to N-HLF, and their effect on cell phenotype was tested. Growth factor levels in the SN were measured by ELISA-based arrays. EGFR activity was blocked by erlotinib (Tarceva, 0.1–0.5 µM). Expression of EGFR, phosphorylated (p)EGFR-1068 and pAkt-473 was significantly higher in IPF-HLF compared with lung fibroblasts from control donors (N-HLF) ( P < 0.05). Apparent expression of p/total EGFR and pAkt-473 was found in the myofibroblastic foci of IPF patients. Erlotinib significantly inhibited IPF-HLF but not N-HLF proliferation. IPF-HLF-SN elevated N-HLF cell number, viability, EGFR expression, and pAkt-473 and ERK1/2 phosphorylation ( P < 0.05). Because high basic fibroblast growth factor levels were found in the IPF-HLF-SN, nintedanib (10–100 nM) was used to inhibit fibroblast growth factor receptor (FGFR) activation. Unlike erlotinib, nintedanib completely blocked IPF-HLF-SNs’ effects on the N-HLF cells in a concentration-dependent manner. In summary, IPF-HLF paracrine signaling elevates EGFR expression, which in turn, affects N-HLF survival. The FGF-EGFR interplay facilitates cellular responses that could potentially promote fibrotic disease. This interplay was successfully blocked by nintedanib.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor prognosis. Inflammatory cytokines play a significant role in IPF pathology. However, the fibroblast itself is also believed to be the primary effector in IPF. We hypothesized that the fibroblasts themselves secrete pro-inflammatory cytokines that could propagate IPF by affecting normal neighboring cells. Thus, we explored the effects of IPF fibroblast derived media on normal fibroblast characteristics.MethodsPrimary IPF/normal tissue derived fibroblast cultures were established and their supernatants were collected (IPF/N-SN, respectively). These supernatants were added to normal fibroblasts. Cell death (caspase-3, western blot), proliferation, viability (WST-1), migration (scratch test) and cell detachment (crystal violet and fibronectin adhesion assays) were tested. 10 inflammatory cytokines were measured by ELISA-based quantitative array. Integrin α5 (ITGA5), pIκBα, p/total STAT3 levels were measured by western blot/IHC. TNF-α involvement was confirmed using Infliximab ®, anti-TNF-α mAb.ResultsThe IPF-SN facilitated fibroblast cell detachment and reduced cell migration (p < 0.05). Nevertheless, these effects were reversed when cells were seeded on fibronectin. The exposure to the IPF-SN also elevated ITGA5 levels, the fibronectin receptor, in addition to NFκB pathway activation (pIκBα↑ 150%, p < 0.05). In accordance, IPF derived fibroblasts were found to express higher ITGA5 than the normal cells (44%↑, p < 0.05). ITGA5 was also expressed in the fibroblastic foci.The IPF-SN contained high TNF-α levels (3-fold, p < 0.05), and Infliximab pretreatment successfully reversed all the above observations.ConclusionWe suggest a possible mechanism in which IPF fibroblast secreted TNF-α modifies neighboring fibroblast cell behavior.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. The IPF-conditioned matrix (IPF-CM) system enables the study of matrix–fibroblast interplay. While effective at slowing fibrosis, nintedanib has limitations and the mechanism is not fully elucidated. In the current work, we explored the underlying signaling pathways and characterized nintedanib involvement in the IPF-CM fibrotic process. Results were validated using IPF patient samples and bleomycin-treated animals with/without oral and inhaled nintedanib. IPF-derived primary human lung fibroblasts (HLFs) were cultured on Matrigel and then cleared using NH4OH, creating the IPF-CM. Normal HLF-CM served as control. RNA-sequencing, PCR and western-blots were performed. HIF1α targets were evaluated by immunohistochemistry in bleomycin-treated rats with/without nintedanib and in patient samples with IPF. HLFs cultured on IPF-CM showed over-expression of ‘HIF1α signaling pathway’ (KEGG, p < 0.0001), with emphasis on SERPINE1 (PAI-1), VEGFA and TIMP1. IPF patient samples showed high HIF1α staining, especially in established fibrous tissue. PAI-1 was overexpressed, mainly in alveolar macrophages. Nintedanib completely reduced HIF1α upregulation in the IPF-CM and rat-bleomycin models. IPF-HLFs alter the extracellular matrix, thus creating a matrix that further propagates an IPF-like phenotype in normal HLFs. This pro-fibrotic loop includes the HIF1α pathway, which can be blocked by nintedanib.

Radiologists should be familiar with the clinical occurrence of synchronous mucinous tumors of the ovary and the appendix associated with PMP and with the typical CT findings of the latter two entities. Alternatively, when the imaging findings suggest ovarian cystic tumor with PMP, the radiologist should be alerted to the probability of a clinically unsuspected appendiceal mucocele and should search for it.

Spontaneous true hemothorax is quite a rare manifestation of a presenting disease. This is a report of two patients, one with bilateral spontaneous massive hemothorax as a presenting manifestation of angiosarcoma involving the lungs and pleura, and the other with unilateral spontaneous hemothorax and hemorrhagic shock as a presenting manifestation of ‘cystic’ chondroblastoma. Differential diagnosis of spontaneous true hemothorax and its evaluation and management are discussed.

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