Factors affecting compliance to intravitreal anti-vascular endothelial growth factor therapy in Indian patients with retinal vein occlusion,age-related macular degeneration,and diabetic macular edema

Purpose:To evaluate the rate of compliance and the reasons for loss to follow-up in Indian patients with diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO) being treated with anti-vascular endothelial growth factor (VEGF) therapy.Methods:This was a retrospective single-center study. Patients with DME, AMD, or RVO were eligible if they initiated anti-VEGF therapy between January 2013 and December 2017. Patients'' data were obtained from hospital electronic records, including the number of injections received, visits, details of follow-up, missed appointments, and reasons for loss to follow-up (>365 days).Results:A total of 648 patients were eligible for the study, of which 334 (51.54%) patients were lost to follow-up. Overall, 343 (64.96%) were males and the overall mean (SD) age was 66.40 (7.44) years. A total of 376 (58.0%) patients had a history of diabetes and 364 (56.2%) patients had a history of hypertension. Further, 127 (38.0), 112 (33.5), and 95 (28.4) had DME, AMD, and RVO, respectively and were lost to follow-up. The most commonly reported reason for loss to follow-up was “non-affordability” (n = 120; 41.1%) followed by “no improvement in vision” (n = 83; 28.4%). “No improvement in vision” (42.2%) and “non-affordability” (37.5%) were higher among patients with DME. No association was found in gender- and treatment-wise distribution of reasons for loss to follow-up.Conclusion:The results showed that around half of the patients with DME, AMD, and RVO were lost to follow-up to intravitreal anti-VEGF therapy, and the most common factors were “non-affordability” and “no improvement in vision.”     

PET imaging of the dopamine transporter with 18F-FECNT: a polar radiometabolite confounds brain radioligand measurements.

18F-2beta-Carbomethoxy-3beta-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane (18F-FECNT), a PET radioligand for the dopamine transporter (DAT), generates a radiometabolite that enters the rat brain. The aims of this study were to characterize this radiometabolite and to determine whether a similar phenomenon occurs in human and nonhuman primate brains by examining the stability of the apparent distribution volume in DAT-rich (striatum) and DAT-poor (cerebellum) regions of the brain. METHODS: Two rats were infused with 18F-FECNT and sacrificed at 60 min. Extracts of brain and plasma were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometric (LC-MS) techniques. Two human participants and 3 rhesus monkeys were injected with 18F-FECNT and scanned kinetically, with serial arterial blood analysis. RESULTS: At 60 min after the injection of rats, 18F-FECNT accumulated to levels about 7 times higher in the striatum than in the cortex and cerebellum. The radiometabolite was distributed at equal concentrations in all brain regions. The LC-MS techniques identified N-dealkylated FECNT as a major metabolite in the rat brain, and reverse-phase HPLC detected an equivalent amount of radiometabolite eluting with the void volume. The radiometabolite likely was 18F-fluoroacetaldehyde, the product expected from the N-dealkylation of 18F-FECNT, or its oxidation product, 18F-fluoroacetic acid. The distribution volume in the cerebellum increased up to 1.7-fold in humans between 60 and 300 min after injection and 2.0 +/- 0.1-fold (mean +/- SD; n = 3) in nonhuman primates between 60 and 240 min after injection. CONCLUSION: An 18F-fluoroalkyl metabolite of 18F-FECNT originating in the periphery confounded the measurements of DAT in the rat brain with a reference tissue model. Its uniform distribution across brain regions suggests that it has negligible affinity for DAT (i.e., it is an inactive radiometabolite). Consistent with the rodent data, the apparent distribution volume in the cerebellum of both humans and nonhuman primates showed a continual increase at late times after injection, a result that may be attributed to entry of the radiometabolite into the brain. Thus, reference tissue modeling of 18F-FECNT will be prone to more errors than analysis with a measured arterial input function.     

Pseudomonas aeruginosa elastase stimulates ERK signaling pathway and enhances IL- 8 production by alveolar epithelial cells in culture

OBJECTIVE AND DESIGN: Bacterial products as well as the host airway inflammatory responses contribute to the pathogenesis of Pseudomonas infections. We sought to determine if Pseudomonas elastase (PE) induces mitogen-activated protein (MAP) kinase activity in association with interleukin-8 (IL-8) production by alveolar epithelial cells. METHODS: We utilized Western blot analysis to detect phosphorylation of signaling intermediates and ELISA was used to measure IL-8 production. RESULTS: We found that PE induces phosphorylation of the extracellular signal-regulated (ERK1/2) proteins of the MAPK pathway in A549 epithelial cells. Similar results were obtained using primary cultures of rabbit alveolar type II epithelial cells. PE also enhanced IL-8 production, which was abolished in the presence of the ERK activation inhibitor U0126. CONCLUSIONS: We conclude that PE activates the ERK1/2 arm of the MAPK pathway and that activation of this pathway results in enhanced IL-8 production. The results demonstrate that PE may augment pulmonary inflammation via cellular signaling that regulates expression of IL-8.     

An intra-articular vascular malformation with a ganglion in a knee

We report a case of an intra-articular vascular malformation occurring simultaneously with a ganglion in a knee joint. We believe this to be the first reported case of an intra-articular vascular malformation occurring simultaneously with a ganglion. The malformation was cauterized resulting in resolution of knee pain. We suggest that vascular malformations be considered in the differential diagnosis of knee pain.     

Ipsilateral mid-third clavicle fracture with grade V acromioclavicular joint dislocation

We report the case of a 20-year-old man with an ipsilateral mid-third clavicle fracture with grade V acromioclavicular joint (ACJ) dislocation. The combination of these two injuries is rare. A literature search produced various treatment algorithms. In this case, the patient was successfully treated with a Bosworth screw.This work was carried out in the Department of Orthopaedics, William Harvey Hospital, Ashford, Kent, UK     

Management of thoraco-lumbar fractures

The immediate surgical goals in the treatment of thoraco-lumbar fractures are decompression of compromised neural structures and stabilization of the vertebral column. If more sophisticated instrumentation is available, e.g. A.O.-fixateur interne or instrument set according to Kluger, stable reposition and reformation of compressed vertebral bodies also becomes possible. The long-term goals are to prevent delayed onset of spinal deformity, pain, and further neurological deficit. Early operative stabilization also shortens hospitalization time and allows immediate ambulation, thus lessening pulmonary, vascular, urological, and psychological complications. The Department of Neurosurgery, Sher-I-Kashmir Institute of Medical Sciences, treated 75 cases of thoraco-lumbar fractures. Out of 75 cases 63 were operated upon: 32 cases by spinal fusion alone and 31 by a combined procedure of decompression and posterior spinal fusion with fibular graft. 52 showed evidence of recovery ranging from moderate to excellent in a follow-up of 2-3 years. Thus surgery resulted not only in giving a stable spine to patients but also good improvement of neurodeficits. Our experiences demonstrate that operative treatment of thoraco-lumbar fractures can give satisfactory results even in situations where sophisticated instrumentation is not available.