Evaluation of prognosis and outcome of small bowel obstruction using the acute general emergency surgical severity-small bowel obstruction score

Background: Small bowel obstruction (SBO) is a common surgical emergency, associated with significant morbidity and mortality specially if strangulated. There was not much used of scoring system for SBO. The aim of the study was to determine the usefulness of acute general emergency surgical severity (AGESS)-SBO score developed by Patrice Wendlling at Mayo Clinic in 2015 to evaluate the prognosis and outcomes of SBO.Methods: 80 patients age ≥13 years who fulfill the study criteria and admitted in surgery ward, Jorhat Medical College and Hospital, Jorhat between May 2020 to October 2021 were identified. The American association for the surgery of trauma (AAST) anatomic score, physiological score and comorbidity score are added to get AGESS-SBO score.Results: The mean age was 41.2 years and males (77.5%) were more affected. Obstructed external hernia (40%) was the most common cause of SBO. 64 patients (80%) were operated and 16 patients were treated conservatively. Complications were seen in 30 patients and 8 patients (10%) died during hospital stay. The median AGESS-SBO score is 5 (IQR 5-6) for complications and 2 (IQR 1.0-2.5) for no complications (p value of 0.0001).Conclusions: Incidence is more in males and obstructed hernia was the commonest cause. Higher the AGESS-SBO score more the complications and so was morbidity and mortality. A score more than 2 has unfavorable outcome

Retinal basal laminar deposits in complement fH/fP mouse model of dense deposit disease

Purpose: Dense deposit disease (DDD) is caused by dysregulation of the alternative pathway of the complement cascade and characterized by electron-dense deposits in the kidney glomerular basement membrane (GBM) and drusen in Bruch's membrane (BrM). Complement factor H (fH) and factor properdin (fP) regulate complement activation; fH inhibits alternative pathway (AP) activation, whereas fP promotes it. We report pathologic changes in eyes of an fH and fP double-mutant mouse, which we previously showed have dense deposits in the GBM and early mortality from nephropathy.Methods: fHm/m, fP−/−, and fHm/m/fP−/− mice were generated on a C57BL/6–129J background. Fundus imaging at 8 weeks of age was followed by analysis via light and electron microscopy. Retinal function was assessed by electroretinography (ERG). Complement levels and localization were tested by immunohistochemistry and ELISA. Retinas of fHm/m/fP−/− mice treated with intraperitoneal injections of an anti-C5 antibody were compared to those of age- and genotype-matched mice injected with an isotype control antibody.Results: fHm/m/fP−/− mice suffered early-onset retinal hypopigmented spots detected using in vivo retinal photography, and histologic examination showed basal laminar deposits (BLamD), degeneration of the photoreceptors, and RPE vacuolization. ERG showed diminished retinal function. The anti-C5 antibody was retina-protective.Conclusions: This unique mouse represents a new model of complement-mediated rapid-onset DDD, and could be useful in exploring the pathologic changes associated with BLamD in age-related macular degeneration

Complement Factor H Mutation W1206R Causes Retinal Thrombosis and Ischemic Retinopathy in Mice

© 2019 American Society for Investigative Pathology Single-nucleotide polymorphisms and rare mutations in factor H (FH; official name, CFH) are associated with age-related macular degeneration and atypical hemolytic uremic syndrome, a form of thrombotic microangiopathy. Mice with the FH W1206R mutation (FH R/R ) share features with human atypical hemolytic uremic syndrome. Herein, we report that FH R/R mice exhibited retinal vascular occlusion and ischemia. Retinal fluorescein angiography demonstrated delayed perfusion and vascular leakage in FH R/R mice. Optical coherence tomography imaging of FH R/R mice showed retinal degeneration, edema, and detachment. Histologic analysis of FH R/R mice revealed retinal thinning, vessel occlusion, as well as degeneration of photoreceptors and retinal pigment epithelium. Immunofluorescence showed albumin leakage from blood vessels into the neural retina, and electron microscopy demonstrated vascular endothelial cell irregularity with narrowing of retinal and choroidal vessels. Knockout of C6, a component of the membrane attack complex, prevented the aforementioned retinal phenotype in FH R/R mice, consistent with membrane attack complex–mediated pathogenesis. Pharmacologic blockade of C5 also rescued retinas of FH R/R mice. This FH R/R mouse strain represents a model for retinal vascular occlusive disorders and ischemic retinopathy. The results suggest complement dysregulation can contribute to retinal vascular occlusion and that an anti-C5 antibody might be helpful for C5-mediated thrombotic retinal diseases

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Retinal Pre-Conditioning by CD59a Knockout Protects against Light-Induced Photoreceptor Degeneration

<div><p>Complement dysregulation plays a key role in the pathogenesis of age-related macular degeneration (AMD), but the specific mechanisms are incompletely understood. Complement also potentiates retinal degeneration in the murine light damage model. To test the retinal function of CD59a, a complement inhibitor, CD59a knockout (KO) mice were used for light damage (LD) experiments. Retinal degeneration and function were compared in WT versus KO mice following light damage. Gene expression changes, endoplasmic reticulum (ER) stress, and glial cell activation were also compared. At baseline, the ERG responses and rhodopsin levels were lower in CD59aKO compared to wild-type (WT) mice. Following LD, the ERG responses were better preserved in CD59aKO compared to WT mice. Correspondingly, the number of photoreceptors was higher in CD59aKO retinas than WT controls after LD. Under normal light conditions, CD59aKO mice had higher levels than WT for GFAP immunostaining in Müller cells, mRNA and protein levels of two ER-stress markers, and neurotrophic factors. The reduction in photon capture, together with the neurotrophic factor upregulation, may explain the structural and functional protection against LD in the CD59aKO.</p></div

Photomicrographs of plastic sections of WT and CD59aKO retinas, and quantification of ONL nuclei.

<p>Histology of mouse retinas showing thinning of the ONL (white brackets) and IS/OS in post-LD WT retinas, while CD59aKO retinas showed less thinning of the ONL and IS/OS (A). Plot of the number of nuclei per column in the ONL. In WT retinas on both the Balb/c and C57BL/6 background, there was a significant decrease of ONL thickness across all sampled retinal regions (a-d) comparing non-light- damaged (NLD) (black line in B and C) and LD (green line in B and C). However, there was a smaller reduction of ONL thickness comparing NLD (blue line in B and C) and LD CD59aKO retinas (red line in B and C). Data are expressed as means ± SD. N = 4. *<i>P</i><0.01, and significance markings refer to overall differences between groups across all four retinal regions (a-d).</p

CD59a expression in mouse retina and mRNA levels of CD59a in NSR and isolated RPE.

<p>Photomicrograph showing CD59a immunolabeling in all layers of mouse retina, RPE and choroid (B), but not in CD59aKO eyes (C). Graph of qPCR results showing that mRNA levels of CD59a in NSR were more than 60-fold higher than that in isolated RPE cells in WT eyes (**<i>P</i><0.001) (D). Data are expressed as means ± SD. N = 4. RPE, retinal pigment epithelium; OS, photoreceptor outer segment; IS, photoreceptor inner segment; ONL, outer nuclear layer; INL, inner nuclear layer; GCL, ganglion cell layer.</p

Immunofluorescence microscopy of GFAP in NLD CD59aKO and WT retinas.

<p>Compared to the labeling limited to the innermost retina in WT mice (C), the GFAP signal was up-regulated in Müller cells of CD59aKO retinas (D). Quantification of fluorescence intensity showed that GFAP was significantly increased in CD59aKO retinas compared to controls (B) (<i>P</i> = 0.03). Data are expressed as means ± SD. N = 4.</p

ERG responses before and after LD.

<p>Before LD, rod-a (<i>P</i><0.05) and rod-b (<i>P</i><0.05) waves were decreased in CD59aKO Balb/c mice compared to WT (A). At day 7 after LD, however, rod-a (<i>P</i> = 0.04) and rod-b (<i>P</i> = 0.01) waves were all larger in CD59aKO compared to WT (A). Data are expressed as means ± SD. N = 4. Similarly, rod-a (<i>P</i><0.05) and rod-b (<i>P</i><0.01) wave amplitudes were smaller in CD59aKO C57BL/6J mice compared to C57BL/6J mice at baseline, and while C57BL/6J mice have diminished ERG amplitudes 10 days after LD, amplitudes in CD59aKO mice remain unchanged (B). Data are expressed as means ± SD. N = 6–7.</p

Quantification of RPE phagocytosis of shed outer segment fragments via immunostaining with anti-rhodopsin antibody.

<p>CD59aKO RPE showed maximal phagosome content 1 h after light onset as characteristic for normal outer segment renewal. Representative retinal cross sections (A) showing opsin immunolabeling (green) and cell nuclei (blue) of CD59aKO outer retina of mice sacrificed at 1 h, 2.5 h, and 13 h after light onset as indicated. In each section, two phagosomes in the RPE are indicated by arrows. Scale bar = 10 μm. Quantification of phagosome counts (B). Eyes from 5 different mice for each time point, and 6 sections of each eye were imaged for each mouse. Data are expressed as mean ± SD. N = 5.</p