Critically ill patients that survive sepsis can develop a Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS), which often leads to extended recovery periods and multiple complications. Here, we utilized a cecal ligation and puncture (CLP) method in mice with the goal of creating a model that concurrently displays all the characteristics of PICS. We observed that, after eight days, mice that survive the CLP develop persistent inflammation with significant myelopoiesis in the bone marrow and spleen. These mice also demonstrate ongoing immune suppression, as evidenced by the decreased total and naïve splenic CD4 and CD8 T cells with a concomitant increase in immature myeloid cells. The mice further display significant weight loss and decreased muscle mass, indicating a state of ongoing catabolism. When PICS mice are challenged with intranasal Pseudomonas aeruginosa, mortality is significantly elevated compared to sham mice. This mortality difference is associated with increased bacterial loads in the lung, as well as impaired neutrophil migration and neutrophil dysfunction in the PICS mice. Altogether, we have created a sepsis model that concurrently exhibits PICS characteristics. We postulate that this will help determine the mechanisms underlying PICS and identify potential therapeutic targets to improve outcomes for this patient population.
The aim of this study was to characterize a large cohort of patients presenting to a single referral center for limbal stem cell deficiency (LSCD).Methods: A retrospective chart review of all patients with a clinical diagnosis of LSCD from 2002 to 2015 was performed. Demographics, etiology, previous ocular surgeries, visual acuity, and treatment were assessed.Results: Seven hundred thirty-eight eyes of 434 patients (51.4% male subjects) were diagnosed with LSCD. The mean presenting age was 42.9 years, 70% presented with bilateral disease, and overall vision was poor. The most common etiologies were congenital aniridia (30.9%), chemical or thermal injuries (20.6%), contact lens (16.8%), Stevens-Johnson syndrome (SJS, 10.4%), and iatrogenic (7.3%). Congenital aniridia had a significantly increased association with glaucoma or ocular hypertension (P , 0.0001). Chemical or thermal injuries (P = 0.0007), SJS (P , 0.0001), and mucous membrane pemphigoid (P , 0.0001) had a significantly increased association with eyelid pathology. The mean logMAR best corrected visual acuity (analysis excluded eyes with light perception and no light perception) at presentation was 1.145 (;20/280). Keratoplasty performed (before presentation at our center) without first addressing the LSCD was seen in 80 eyes; all keratoplasties failed due to recurrence of the LSCD.
Conclusions:Patients presenting with LSCD were on average middle aged without sex predominance. LSCD was most commonly bilateral, comprised a wide range of etiologies, and decreased vision substantially. Ocular comorbidities may need to be treated before treating the LSCD surgically. Finally, not addressing the LSCD (primary issue) first can result in keratoplasty failure.
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