BackgroundChronic inflammation is a characteristic feature of diabetic cutaneous wounds. We sought to delineate novel mechanisms involved in the impairment of resolution of inflammation in diabetic cutaneous wounds. At the wound-site, efficient dead cell clearance (efferocytosis) is a pre-requisite for the timely resolution of inflammation and successful healing.Methodology/Principal FindingsMacrophages isolated from wounds of diabetic mice showed significant impairment in efferocytosis. Impaired efferocytosis was associated with significantly higher burden of apoptotic cells in wound tissue as well as higher expression of pro-inflammatory and lower expression of anti-inflammatory cytokines. Observations related to apoptotic cell load at the wound site in mice were validated in the wound tissue of diabetic and non-diabetic patients. Forced Fas ligand driven elevation of apoptotic cell burden at the wound site augmented pro-inflammatory and attenuated anti-inflammatory cytokine response. Furthermore, successful efferocytosis switched wound macrophages from pro-inflammatory to an anti-inflammatory mode.Conclusions/SignificanceTaken together, this study presents first evidence demonstrating that diabetic wounds suffer from dysfunctional macrophage efferocytosis resulting in increased apoptotic cell burden at the wound site. This burden, in turn, prolongs the inflammatory phase and complicates wound healing.

Teprotumumab attenuates the actions of both IGF-1 and TSH in fibrocytes. Specifically, it blocks the induction of proinflammatory cytokines by TSH. These results provide, at least in part, the molecular rationale for interrogating the therapeutic efficacy of this antibody in TAO.

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Purpose To characterize the presenting characteristics, pre-operative clinical activity score (CAS), surgical approach, and visual outcomes in patients with thyroid eye disease undergoing repeat orbital decompression for recurrent or recalcitrant compressive optic neuropathy. Methods The medical records of patients with recurrent or recalcitrant compressive optic neuropathy (CON) undergoing repeat orbital decompressions were retrospectively reviewed. The primary outcome measures included pre- and post-operative Humphrey visual field mean deviation, visual acuity measured in logarithm of the minimal angle of resolution, color vision measured by Ishihara plates, and presence of relative afferent pupillary defect. Details of the surgical procedure and each patient’s CAS at presentation were also recorded. Results Six patients, 9 orbits, with a mean pre-operative CAS of 3.8 were included in this review. The mean time between initial decompression and presentation to our center for recurrent or persistent CON symptoms was 8.6 years (range, 1–15 years). At presentation, the average HVF mean deviation was −16.5 (standard deviation (SD): 8.8), improving to −3.8 (2.4) post-operatively with a mean of 9.3 months follow-up (mean improvement of 75%). Pre-operative visual acuity was 0.34 (0.23) LogMAR, improving to 0.05 (0.10) logMAR with a mean follow up of 10.4 months. Pre- to post-operative comparisons of clinical measures all showed statistically significant improvement (p<0.05). Eight eyes presented with decreased visual acuity (any VA < 20/20), 4 with decreased color vision (any color vision < 11), and 1 with a relative afferent pupillary defect and all of these patients demonstrated improvement following repeat orbital decompression. Conclusions In patients with thyroid eye disease, symptoms of recurrent compressive optic neuropathy occurred up to 15 years following initial orbital decompression underscoring the smoldering, progressive nature of the disease. Repeat decompression which focused on the orbital apex resulted in visual improvement in all 6 patients. Despite clinical evidence of compressive optic neuropathy, the mean CAS of these patients at presentation was only 3.8, highlighting the importance of close monitoring of patients with thyroid eye disease following decompression regardless of the external manifestations of disease activity.

We present fluoroscopic images of the aortic arch and its branches obtained in a first year medical gross anatomy teaching laboratory after an aberrant right subclavian artery was discovered during dissection. The aortic arch and its branches in the cadaver were filled with contrast medium in molten agar. After the agar solidified, a portable fluoroscope was used to obtain radiographic images. These post-mortem images were then compared with computed tomography images obtained while the individual was living. The embryology, prevalence, and clinical findings of this arterial variation are reviewed, and the importance of recognizing the presence of an aberrant right subclavian artery before performing various procedures is discussed. This exercise gave students the unique opportunity to compare the three-dimensional anatomy seen in the dissection laboratory with the two-dimensional presentation of that same anatomy in the radiographic images that they will see in clinical practice.

A 41-year-old female with Sjogren syndrome presented with a 5-month history of bilateral upper eyelid swelling. Incisional biopsy of the left lacrimal gland revealed mucosa-associated lymphoid tissue lymphoma. Due to bilateral severe dry eyes, the patient declined external beam radiotherapy and systemic rituximab was initiated. The patient responded well to intravenous rituximab and the follow-up CT revealed decrease in size of both lacrimal glands. Eleven months after systemic rituximab, the patient developed bilateral lacrimal gland recurrence. The patient declined external beam radiotherapy. Intralesional rituximab (50 mg/1 ml) was injected into the left lacrimal gland, followed by injection in the right lacrimal gland 7 months later. Twenty-three months follow-up after the injection into the right lacrimal gland, there was significant decrease in size of bilateral lacrimal glands and subjective improvement of dry eye symptoms. This case highlights the intralesional rituximab as an alternative therapy for recurrent orbital mucosa-associated lymphoid tissue lymphoma in selected cases.

A 74-year-old man with no previous history of eye disease (Fig 1 A), presented with episodes of intermittent haemolacria occurring over a five-month period. When the left upper lid was everted, a raised pigmented lesion was seen on the tarsal conjunctiva (Fig 1 B). Histopathology (H&E) revealed a conjunctival melanoma composed of nests within the substantia propria. Marked pleomorphism, atypia, mitotic figures, and multinucleated tumor giant cells (Fig 1 C arrow) were seen. "Melanoma cocktail" immunohistochemical stain highlighted the tumor cells (Fig 1 D asterisk). PET/CT scan and a sentinel lymph node biopsy were negative for metastatic disease.

Reversal of anisocoria following instillation of apraclonidine 0.5% has been reported in Horner syndrome caused by lesions of the central and peripheral nervous system. The shortest documented latency between symptom onset and a positive apraclonidine test is 36 hours, occurring in a patient with a pontomedullary infarct. We present the case of a 69-year-old man with Horner syndrome due to thalamic hemorrhage in whom apraclonidine testing demonstrated reversal of anisocoria 4 days after symptom onset. This is the first reported case of a positive apraclonidine test in a Horner syndrome caused by a lesion at this site. It suggests that apraclonidine testing is useful in confirming the diagnosis within days of onset even in a lesion located at the most proximal portion of the oculosympathetic pathway.