Shigella IpaH9.8 limits GBP1-dependent LPS release from intracytosolic bacteria to suppress caspase-4 activation.

Pyroptosis is an inflammatory form of cell death induced upon recognition of invading microbes. During an infection, pyroptosis is enhanced in interferon-gamma-exposed cells via the actions of members of the guanylate-binding protein (GBP) family. GBPs promote caspase-4 (CASP4) activation by enhancing its interactions with lipopolysaccharide (LPS), a component of the outer envelope of Gram-negative bacteria. Once activated, CASP4 promotes the formation of noncanonical inflammasomes, signaling platforms that mediate pyroptosis. To establish an infection, intracellular bacterial pathogens, like Shigella species, inhibit pyroptosis. The pathogenesis of Shigella is dependent on its type III secretion system, which injects ~30 effector proteins into host cells. Upon entry into host cells, Shigella are encapsulated by GBP1, followed by GBP2, GBP3, GBP4, and in some cases, CASP4. It has been proposed that the recruitment of CASP4 to bacteria leads to its activation. Here, we demonstrate that two Shigella effectors, OspC3 and IpaH9.8, cooperate to inhibit CASP4-mediated pyroptosis. We show that in the absence of OspC3, an inhibitor of CASP4, IpaH9.8 inhibits pyroptosis via its known degradation of GBPs. We find that, while some LPS is present within the host cell cytosol of epithelial cells infected with wild-type Shigella, in the absence of IpaH9.8, increased amounts are shed in a GBP1-dependent manner. Furthermore, we find that additional IpaH9.8 targets, likely GBPs, promote CASP4 activation, even in the absence of GBP1. These observations suggest that by boosting LPS release, GBP1 provides CASP4-enhanced access to cytosolic LPS, thus promoting host cell death via pyroptosis.

Cost-effectiveness analysis of endovascular versus open repair of abdominal aortic aneurysm in a high-volume center.

OBJECTIVE: Endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAAs) is the standard treatment for anatomically suitable patients. EVAR has been associated with a lower perioperative morbidity and mortality compared with open surgical repair (OSR) at the expense of increased reinterventions and costs. We aimed to compare the outcomes of EVAR and OSR for elective AAA repair. The primary end point was cost per QALY at 3 years. Secondary end points were perioperative morbidity and mortality; freedom from reintervention; length of hospital, high-dependency unit, and intensive care unit stay; and freedom from all-cause mortality. METHODS: The project was approved by the Galway Clinical Research Ethics Committee. This project followed the Declaration of Helsinki. This was an audit of interventions that had already taken place. No active clinical intervention was undertaken, and patients' anonymity was preserved; thus, individual patient consent was not obtained. Data on all elective AAA repairs at a tertiary referral vascular center were collected from 2002 to 2015. Demographics and outcomes were reported according to the Society for Vascular Surgery guidelines. QALY was measured on the basis of a quality-adjusted time without symptoms or toxicity assessment. Data were analyzed using parametric and nonparametric tests. RESULTS: Between 2002 and 2015, a total of 494 patients required elective AAA surgery; 401 underwent EVAR and 93 underwent OSR. Demographics and vascular-related risk factors were similar in both groups. Median (interquartile range) cost per QALY at 3 years was €5776 (€5541-€6481) for EVAR vs €7101 (€5812-€8952) for OSR (P < .001). EVAR was associated with reduced perioperative morbidity (12.2% vs 50%; P < .001). There was no significant association between procedure and perioperative mortality (EVAR, 1.7%; OSR, 4.3%; P = .130). There was no significant association found between the procedure and reintervention (P = .502). Our subgroup analysis found no association between procedure and improvement in all-cause mortality, QALYs, costs, or cost per QALY. CONCLUSIONS: EVAR is cost-effective with improved cost per QALY compared with OSR.

Greenhouse Gas Emissions in the United States Food System: Current and Healthy Diet Scenarios.

We estimate the impact on greenhouse gas emissions (GHGE) of shifting from the current average United States diet to four alternative diets that meet the 2010 Dietary Guidelines for Americans (DGA). In contrast to prior studies, which rely on process-based life-cycle-analysis GHGE estimates from the literature for particular food items, we combine a diet model, an environmentally extended input-output model of energy use in the U.S. food system, and a biophysical model of land use for crops and livestock to estimate food system GHGE from the combustion of fossil fuels and from biogenic sources, including enteric fermentation, manure management, and soil management. We find that an omnivore diet that meets the DGA while constraining cost leaves food system GHGE essentially unchanged relative to the current baseline diet (985 000 000 tons of CO2 eq or 3191 kilograms of CO2 eq per capita per year), while a DGA-compliant vegetarian and a DGA-compliant omnivore diet that minimizes energy consumption in the food system reduce GHGE by 32% and 22%, respectively. These emission reductions were achieved mainly through quantity and composition changes in the meat, poultry, fish; dairy; and caloric sweeteners categories. Shifting from current to healthy diets as defined by the DGA does not necessarily reduce GHGE in the U.S. food system, although there are diets, including two presented here and by inference many others, which can achieve a reduction in GHGE.

Q-TWiST and Cost-Effectiveness Analysis of Endovascular versus Open Repair for Ruptured Abdominal Aortic Aneurysms in a High Deliberate Practice Volume Center.

BACKGROUND: The objective of the study was to compare the cost-effectiveness of endovascular aortic repair (rEVAR) versus open surgical repair (rOSR) for ruptured abdominal aortic aneurysm (rAAA), where rEVAR is regularly performed outside of instructions for use (IFUs) (shorter and more angulated necks). Primary end point is incremental cost-effectiveness ratio (ICER) of rEVAR versus rOSR and aneurysm-related mortality. Secondary end points are cost per quality-adjusted life years (QALYs), perioperative morbidity and mortality, reintervention, and all-cause mortality. METHODS: All rAAA repairs performed between 2002 and 2016 in a single center were scrutinized. Between 2002 and 2007, most rAAAs were repaired using rOSR. From 2007 to 2016, we implemented a rEVAR with an anatomically possible protocol. During this time, severe angulation was rarely seen as a contraindication to rEVAR, and rEVAR was performed on aneurysms with an infrarenal aortic neck cranial to the aneurysm with a diameter of 20-33 mm and a length of at least 5 mm. Demographics and outcomes were reported according to the Society for Vascular Surgery guidelines. QALY was measured based on quality of time spent without symptoms of disease or toxicity of treatment (Q-TWiST) assessment. RESULTS: Eight hundred aneurysm surgeries were performed; of these, 135 were emergency surgeries of which 88 were for rAAA; (42 rEVARs and 46 rOSRs). Primary technical success (rEVAR 89.1% vs. rOSR 87.8%; P = 0.1), perioperative morbidity (rEVAR 56.5% vs. rOSR 64.3%; P = 0.457), and mortality (rEVAR 26.1% vs. rOSR 28.6%; P = 0.794) were nonsignificantly favorable in rEVAR patients. Freedom from reintervention was significantly lower in rEVAR patients at 3 years (rEVAR 74% vs. rOSR 90%; P = 0.038). Three-year aneurysm-related survival (rEVAR 65% vs. rOSR 62%; P = 0.848) and all-cause survival (rEVAR 56% vs. rOSR 51%; P = 0.577) were higher in rEVAR patients. At 3 years, rEVAR patients had a higher QALY of 1.671 versus OSR of 1.549 (P = 0.502). Operating room (P = 0.001) and total accommodation costs (P = 0.139) were lower in rEVAR patients, while equipment (P < 0.001), surveillance, and reintervention (P < 0.001) costs were higher. Median cost of rEVAR at 3 years was €23,352 vs. €20,494 for OSR (P < 0.084) (power>80%). Median cost per QALY of rEVAR at 3 years was €13,974 vs. €13,230 for rOSR (P = 0.296). ICER for rEVAR versus rOSR was €23,426 (95% confidence interval [CI] < €0 to > €30,000). At 3 years, the area under the curve and 95% CI for Q-TWiST was higher in rEVAR compared with OSR (rEVAR 500.819 vs. rOSR 437.838). CONCLUSIONS: There is no significant difference in cost or QALYs between rEVAR and rOSR even when rEVAR is performed on complex cases outside of IFU (shorter and more angulated necks). There is a significantly higher freedom from secondary intervention in rOSR patients compared with rEVAR patients at 3 years.

Quality of time spent without symptoms of disease or toxicity of treatment for transmetatarsal amputation versus digital amputation in diabetic patients with digital gangrene.

Aim We aim to compare the outcome of diabetic patients with gangrenous toes who were managed initially either by digital amputation or by transmetatarsal amputation. The null hypothesis is that transmetatarsal amputation had less theatre trips and better healing. Materials and Methods A parallel observational comparative study of all diabetic patients who underwent either digital or transmetatarsal amputation in a tertiary referral center from 2002 through 2015. Comorbid conditions, subsequent amputations, hospital stay, and readmission were noted. Results A total of 223 patients underwent minor amputation during the study period, of which 147 patients were diabetic and 76 patients were non-diabetic. Seventy-seven patients had digital amputation and 70 transmetatarsal amputation in diabetic patients. Demographics were similar in both groups. The median time to major amputation was (400 ± IQR 1205 days) in the digital amputation group, compared to 690 ± IQR 891 days in the transmetatarsal amputation group ( P = 0.974). 29.9% of digital amputations and 15.7% of transmetatarsal amputations in diabetic patients, required minor amputations or revision procedures ( P = 0.04). Median length of hospital stay was (20 days, IQR 27) in the digital group and (17 days, IQR17) in the transmetatarsal amputation group ( P = 0.17). Need for re-admission was 48.1% in digital patients compared to 50% in transmetatarsal amputation patients ( P = 0.81). Quality of time spent without symptoms of disease or toxicity of treatment (Q-TWiST) was (315 days, IQR 45) in digital group and (346 days, IQR 48) in the transmetatarsal amputation patients ( P = 0.099). Conclusion Despite the lack of statistical significance, transmetatarsal amputation offered better outcome in the diabetic patients, with less re-intervention rate, shorter hospital stays, less theatre trips, and longer time without toxicity (TWiST).

Analysis of cataract referrals from community optometrists and general practitioners and subsequent clinic visit outcomes in a university hospital in the west of Ireland.

BACKGROUND: Studies published from hospitals in other countries have reported rates of between 69 and 90% of cataract referrals being listed for surgery (1-3). This potentially represents unnecessary outpatient appointments, time off work and transport costs for patients and carers (2). AIMS: Our first primary endpoint was to assess the number of cataract referrals listed for surgery. Our second primary endpoint was to assess the number of cataract referrals which included the following: (i) that visual loss from the cataract resulted in a detrimental effect on the patient's lifestyle, (ii) that the patient was willing to have surgery and (iii) that the patient was symptomatic from their cataract. METHODS: This project followed the Declaration of Helsinki. This was a retrospective study. RESULTS: Between February 2021 and February 2022, 198 patients were seen in Mr. PM's cataract clinic. Overall, 129 patients (67.5%) were listed for cataract surgery. Forty-seven referrals (23.7%) reported that the cataract was having a detrimental effect on the patient's life and these patients were more likely to be listed for surgery (93.6% vs. 59.2%, p = 0.00). Twenty-five referrals (12.6%) reported that the patient was willing to undergo surgery and these patients were more likely to be listed for surgery (88% vs. 64.8%, p = 0.02). A total of 130 referrals (65.7%) reported that the patient was symptomatic from their cataract and these patients were more likely to be listed for surgery (81.5% vs. 38.3%, p = 0.00). CONCLUSIONS: It is possible that an appropriately focussed referral form will aid in triaging cataract referrals and potentially reduce unnecessary appointments.

Post-farmgate food value chains make up most of consumer food expenditures globally.

Progress towards many United Nations Sustainable Development Goals depends on interventions in food value chains, yet data and methods have thus far limited the production of cross-nationally comparable estimates of food value chains' magnitudes. Here we develop a standardized method and data series to estimate the distribution of consumer food expenditures between value-added activities on farms and in the post-farmgate value chain. Using data from 61 countries over 2005-2015, representing 90% of the global economy, we show that farmers receive, on average, 27% of consumer expenditure on foods consumed at home and a far lower percentage of food consumed away from home. That figure consistently falls in the 16-38% range for middle- and high-income countries and falls significantly as incomes rise. The large and growing post-farmgate food value chain merits greater attention as the world grapples with the economic, environmental and social impacts of food systems.

Analysing the Society for Vascular Surgery and American Association for Vascular Surgery scoring systems for outcomes post-endovascular aortic repair.

BACKGROUND AND AIMS: Assess the association between the Society for Vascular Surgery/American Association for Vascular Surgery (SVS/AVSS) (Rutherford et al., J Vasc Surg 26: 517-38, 1997; Chaikof et al., J Vasc Surg 35:1061-6, 2002) medical comorbidity scoring scheme (MCS), and the global scoring system (GS) and major morbidity and mortality after elective endovascular aneurysm repair. Primary end points were peri-operative morbidity and mortality. Secondary end points were intensive care unit admission, high dependency unit admission, total stay > 5 days and 2-year mortality. METHODS: The project was approved by the Galway Clinical Research Ethics Committee. This project followed the Declaration of Helsinki. Binary logistic regression was performed to assess the association of the scores and their individual components with the primary and secondary outcomes. Results were reported as odds ratio (OR) per point increase in score with 95% confidence intervals (CI) and the Hosmer-Lemeshow (HL). RESULTS: Between 2002 and 2015, 401 patients underwent elective EVARs. MCS was calculated for 396 patients while GS was calculated for 183 patients. The MCS (OR 1.906, CI 1.017-3.574, p = 0.044) was associated with perioperative morbidity. The MCS was associated with perioperative mortality (OR 8.875, CI 1.918-41.070, p = 0.005). The GS was associated with perioperative morbidity (OR 11.929, CI 1.151-123.584, p = .038) but not associated with perioperative mortality (OR 3.62, CI 0.006-2118.148, p = .692). CONCLUSIONS: The MCS shows association with perioperative morbidity and mortality. GS shows association with perioperative morbidity but not perioperative mortality; however, this may be due to our study being underpowered. We believe that the analysis of higher numbers of patients could unmask trends in both of these scores and individual components of both scores changed.

Effects of Introducing a Secure Web-based Messenger Application for Communication Among Non-consultant Hospital Doctors (NCHDs).

INTRODUCTION:  Use of web-based messaging applications to communicate clinical information is common between non-consultant hospital doctors (NCHDs). This study sought to assess web-based messenger use in NCHDs following the introduction of a more secure alternative to WhatsApp (WhatsApp, Inc., Menlo Park, CA, USA). METHODS:  A 10-item survey was undertaken on two NCHD cohorts. The second cohort received training on data protection and an alternative application to WhatsApp. Quantitative data analysis was conducted using the IBM Statistical Package for Social Sciences (SPSS) (IBM SPSS Statistics, Armonk, NY). RESULTS:  The total response rate across both groups was 63% (N = 68). The majority of respondents used WhatsApp to communicate clinical information. In the second cohort, fewer NCHDs shared identifiable sensitive patient information 97% (n = 29/30) vs 81% (n = 25/31) and fewer NCHDs shared/stored clinical images. DISCUSSION:  WhatsApp use is common among NCHDs. An alternative means of communication can improve the safety of patient data. NCHDs require more training on data protection laws and their own responsibilities.