Diabetic retinal neurodegeneration as a form of diabetic retinopathy

Purpose

To review the evidence supporting diabetic retinal neurodegeneration (DRN) as a form of diabetic retinopathy.

Method

Review of literature.

Results

DRN is recognized to be a part of retinopathy in patients with diabetes mellitus (DM), in addition to the well-established diabetic retinal vasculopathy (DRV). DRN has been noted in the early stages of DM, before the onset of clinically evident diabetic retinopathy. The occurrence of DRN has been confirmed in animal models of DM, histopathological examination of donor’s eyes from diabetic individuals and assessment of neural structure and function in humans. DRN involves alterations in retinal ganglion cells, photoreceptors, amacrine cells and bipolar cells, and is thought to be driven by glutamate, oxidative stress and dysregulation of neuroprotective factors in the retina. Potential therapeutic options for DRN are under evaluation.

Conclusions

Literature is divided on the temporal relation between DRN and DRV, with evidence of both precedence and simultaneous occurrence. The relationship between DRN and multi-system neuropathy in DM is yet to be evaluated critically.

     

Ultra-wide field retinal imaging: A wider clinical perspective

The peripheral retina is affected in a variety of retinal disorders. Traditional fundus cameras capture only a part of the fundus even when montaging techniques are used. Ultra-wide field imaging enables us to delve into the retinal periphery in greater detail. It not only facilitates assessing color images of the fundus, but also fluorescein angiography, indocyanine green angiography, fundus autofluorescence, and red and green free images. In this review, a literature search using the keywords “ultra-widefield imaging”, “widefield imaging”, and “peripheral retinal imaging” in English and non-English languages was done and the relevant articles were included. Ultra-wide field imaging has made new observations in the normal population as well as in eyes with retinal disorders including vascular diseases, degenerative diseases, uveitis, age-related macular degeneration, retinal and choroidal tumors and hereditary retinal dystrophies. This review aims to describe the utility of ultra-wide field imaging in various retinal disorders.     

Complication avoidance protocols in endoscopic pituitary adenoma surgery: a retrospective cohort study in 514 patients

Pituitary - To evaluate the impact of using consistent complication-avoidance protocols in patients undergoing endoscopic pituitary adenoma surgery including techniques for avoiding anosmia,...     

4-Hydroxy TEMPO Attenuates Dichlorvos Induced Microglial Activation and Apoptosis

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Collateral Ligament Laxity in Knees: What Is Normal?

Background

Proper alignment and balancing of soft tissues of the knee are important goals for TKA. Despite standardized techniques, there is no consensus regarding the optimum amount of collateral ligament laxity one should leave at the end of the TKA.

Questions/purposes

I asked (1) what is the collateral laxity in young healthy volunteers, and (2) is there a difference in collateral laxity between males and females.

Methods

The femorotibial mechanical angle (FTMA) was measured in 314 knees in healthy volunteers aged 19 to 35 years. Subjects with a history of pain, malalignment, dysplasia, or trauma were excluded. Twenty-five knees were excluded because the hip center could not be acquired, and 22 were excluded because of a history of pain and trauma, leaving 267 knees for inclusion in the study. Of these, 155 were from men and 112 were from women. A validated method using a computer navigation system was used to obtain the measurements. A 10-Nm torque was used to stress the knee in varus and valgus at 0° extension and 15° flexion. An independent t-test and ANOVA were applied to the data to calculate any significant difference between groups (p < 0.05).

Results

The mean (SD) unstressed supine FTMA was varus of 1.2° (SD, 4°) in 0° extension and varus of 1.2° (SD, 4.4°) in 15° flexion (p = 0.88). On varus torque of 10 Nm, the supine FTMA changed by a mean of 3.1° (SD, 2°) (95% CI, 2.4°–3.8°; p < 0.001) in 0° extension and 6.9° (SD, 2.6°) (95% CI, 6.2°–7.7°; p < 0.001) in 15° flexion. On valgus torque of 10 Nm, the FTMA changed by a mean of 4.6° (SD, 2.2°) (95% CI, 3.9°–5.3°; p < 0.001) in 0° extension and 7.9° (SD, 3.4°) (95% CI, 7.1°–8.7°; p < 0.001) in 15° flexion. The mean unstressed FTMA in 0° extension was varus of 1.7° (SD, 4°) in men and 0.4° (SD, 3.9°) in women (p = 0.01). Differences in collateral ligament laxity were seen between men and women (p < 0.001 for valgus torque and 0.035 for varus torque in 15° flexion). With valgus torque at 0° flexion, the supine FTMA change was valgus of 4.2° (SD, 2.0°) for men and 5.0° (SD, 2.4°) for women, while at 15° flexion the FTMA change was valgus 7.6° (SD, 3.6°) for men and 8.3° (SD, 3.2°) for women With varus torque at 0° flexion, additional varus was −3.0° (SD, 1.8°) for men and −3.3° (SD, 2.2°) for women, while at 15° flexion, varus was −7.0° SD, (2.5°) for men and −6.9° (SD, 2.8°) for women.

Conclusions

The collateral laxity in young healthy volunteers was quantified in this study. The collateral ligament laxity is variable in different persons. In addition, ligaments in women are more lax than in men in valgus stress.

Clinical Relevance

This study was conducted on young, healthy knees. Whether the findings are applicable to arthritic knees and replaced knees needs additional evaluation. However the findings provide a baseline from which to work in the evaluation of arthritic knees and in the case of TKA.     

Selfie fundus imaging for diabetic retinopathy screening

BackgroundRegular screening for retinopathy and timely intervention reduces blindness from diabetes by 90%. Screening is currently dependent on the interpretation of images captured by trained technicians. Inherent barriers of accessibility and affordability with this approach impede widespread success of retinopathy screening programs. Herein, we report our observations on the potential of a novel approach, Selfie Fundus Imaging (SFI), to enhance diabetic retinopathy screening.MethodsThe study was undertaken over a two-month period during COVID 19 lockdown. 60 diabetic patients participated in the study. Retinal images were captured using three different approaches, handheld smartphone-based photographs captured by patients themselves after a short video-assisted training session (SFI group), and smartphone-based photographs captured by a trained technician and photographs taken on desktop conventional digital fundus camera (Gold standard). Sensitivity and kappa statistics was determined for retinopathy and macular oedema grading.FindingsMean age of the study participants was 52.4 years ± 9.8 years and 78% were men. Of 120 images captured using SFI, 90% were centred-gradable, 8% were decentred-gradable and 2% were ungradable. 82% patients captured the image within a minute (majority by 31–45 s). The sensitivity of SFI to detect diabetic retinopathy was 88.39%. Agreement between SFI grading and standard fundus photograph grading was 85.86% with substantial kappa (0.77). For the detection of diabetic macular oedema, the agreement between SFI images and standard images was 93.67, with almost perfect kappa (0.91).ConclusionFundus images were captured by patients using SFI without major difficulty and were comparable to images taken by trained specialist. With greater penetrance, advances, and availability of mobile photographic technology, we believe that SFI would positively impact the success of diabetic retinopathy screening programs by breaking the barriers of availability, accessibility, and affordability. SFI could ensure continuation of screening schedules for diabetic retinopathy, even in the face a highly contagious pandemic.Subject terms: Outcomes research, Retinal diseases, Physical examination     

Exosomes secreted by prostate cancer cells under hypoxia promote matrix metalloproteinases activity at pre-metastatic niches

Approximately, 30 000 men die from prostate cancer (PCa) every year in the United States, mainly due to the metastasis. Thus, the key events associated with PCa metastasis are under rigorous investigation, with recent studies showing that preparation of pre-metastatic niches (PMN) in distant organs is an important step. However, the molecular basis for PMN preparation is still unclear. Hypoxia in primary tumors promotes aggressiveness; however, its precise role in metastasis is not clear. We recently reported that exosomes secreted by PCa cells under hypoxia promote stemness and invasiveness in naïve PCa cells; however, whether these extracellular vesicles also influence PMN remains unknown. In the present study, we isolated exosomes from human PCa PC3 cells under normoxic (21% O₂, exosomes secreted under normoxic condition [Exo^Normoxic]) and hypoxic (1% O₂, exosomes secreted under hypoxic condition [Exo^Hypoxic]) conditions, and characterized their effect (10 µg exosomes, intraperitoneal (IP) treatment every 48 hours for 4 weeks) on key biomarkers associated with PMN in nude mice. Whole animal fluorescence imaging showed that Exo^Hypoxic treatment promotes matrix metalloproteinases (MMPs) activity in several putative metastatic sites. Histological studies confirmed that Exo^Hypoxic treatment enhanced the level of MMP2, MMP9, and extracellular matrix proteins (fibronectin and collagen) as well as increased the number of CD11b+ cells at selective PMN sites. Furthermore, proteomic profiling of exosomes by liquid chromatography/mass spectrometry identified cargo proteins in Exo^Normoxic and Exo^Hypoxic as well as distinct canonical pathways targeted by them. These results suggest that exosomes secreted by PCa cells under hypoxia plausibly remodel distant PMN, and thus, could be a potential target to control metastatic PCa.     

Pentoxifyline versus prednisolone for severe alcoholic hepatitis: A randomized controlled trial

AIM: To compare the efficacy of pentoxifylline and prednisolone in the treatment of severe alcoholic hepatitis, and to evaluate the role of different liver function scores in predicting prognosis. METHODS: Sixty-eight patients with severe alcoholic hepatitis (Maddrey score ≥ 32) received pentoxifylline ( n = 34, group Ⅰ) or prednisolone ( n = 34, group Ⅱ) for 28 d in a randomized double-blind controlled study, and subsequently in an open study (with a tapering dose of prednisolone) for a total of 3 mo, and were followed up over a period of 12 mo. RESULTS: Twelve patients in group Ⅱ died at the end of 3 mo in contrast to five patients in group Ⅰ. The probability of dying at the end of 3 mo was higher in group Ⅱ as compared to group Ⅰ (35.29% vs 14.71%, P = 0.04; log rank test). Six patients in group Ⅱ developed hepatorenal syndrome as compared to none in group Ⅰ. Pentoxifylline was associated with a significantly lower model for end-stage liver disease (MELD) score at the end of 28 d of therapy (15.53 Maddrey score was associated with increased mortality. CONCLUSION: Reduced mortality, improved risk-benefit profile and renoprotective effects of pentoxifylline compared with prednisolone suggest that pentoxifylline is superior to prednisolone for treatment of severe alcoholic hepatitis.