Computed tomography calcium score scan for attenuation correction of N-13 ammonia cardiac positron emission tomography: effect of respiratory phase and registration method

The use of coronary calcium scoring (CaScCT) for attenuation correction (AC) of 13N-ammonia PET/CT studies (NH3) is still being debated. We compare standard ACCT to CaScCT using various respiratory phases and co-registration methods for AC. Forty-one patients underwent a stress/rest NH3. Standard ACCT scans and CaScCT acquired during inspiration (CaScCTinsp, 26 patients) or expiration (CaScCTexp, 15 patients) were used to correct PET data for photon attenuation. Resulting images were compared using Pearson's correlation and Bland-Altman (BA) limits of agreement (LA) on segmental relative and absolute coronary blood flow (CBF) using both manual and automatic co-registration methods (rigid-body and deformable). For relative perfusion, CaScCTexp correlates better than CaScCTinsp with ACCT when using manual co-registration (r=0.870; P<0.001 and r=0.732; P<0.001, respectively). Automatic co-registration provides the best correlation between CaScCTexp and ACCT for relative perfusion (r=0.956; P<0.001). Both CaScCTinsp and CaScCTexp yielded excellent correlations with ACCT for CBF when using manual co-registration (r=0.918; P<0.001; BA mean bias 0.05ml/min/g; LA: −0.42 to +0.3ml/min/g and r=0.97; P<0.001; BA mean bias 0.1ml/min/g; LA: −0.65 to +0.5ml/min/g, respectively). The use of CaScCTexp and deformable co-registration is best suited for AC to quantify relative perfusion and CBF enabling substantial radiation dose reductio

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Computed tomography calcium score scan for attenuation correction of N-13 ammonia cardiac positron emission tomography:effect of respiratory phase and registration method

<p>The use of coronary calcium scoring (CaScCT) for attenuation correction (AC) of N-13-ammonia PET/CT studies (NH3) is still being debated. We compare standard ACCT to CaScCT using various respiratory phases and co-registration methods for AC. Forty-one patients underwent a stress/rest NH3. Standard ACCT scans and CaScCT acquired during inspiration (CaScCTinsp, 26 patients) or expiration (CaScCTexp, 15 patients) were used to correct PET data for photon attenuation. Resulting images were compared using Pearson's correlation and Bland-Altman (BA) limits of agreement (LA) on segmental relative and absolute coronary blood flow (CBF) using both manual and automatic co-registration methods (rigid-body and deformable). For relative perfusion, CaScCTexp correlates better than CaScCTinsp with ACCT when using manual co-registration (r = 0.870; P <0.001 and r = 0.732; P <0.001, respectively). Automatic co-registration provides the best correlation between CaScCTexp and ACCT for relative perfusion (r = 0.956; P <0.001). Both CaScCTinsp and CaScCTexp yielded excellent correlations with ACCT for CBF when using manual co-registration (r = 0.918; P <0.001; BA mean bias 0.05 ml/min/g; LA: -0.42 to +0.3 ml/min/g and r = 0.97; P <0.001; BA mean bias 0.1 ml/min/g; LA: -0.65 to +0.5 ml/min/g, respectively). The use of CaScCTexp and deformable co-registration is best suited for AC to quantify relative perfusion and CBF enabling substantial radiation dose reduction.</p>

Geospatial Mapping of Pediatric Surgical Capacity in North Kivu, Democratic Republic of Congo.

BACKGROUND: Despite recent attention to the provision of healthcare in low- and middle-income countries, improvements in access to surgical services have been disproportionately lagging. METHODS: This study analyzes the geographic variability in access to pediatric surgical services in the province of North Kivu, Democratic Republic of Congo (DRC). On-site data collection was conducted using the Global Assessment of Pediatric Surgery tool. Spatial distribution of providers was mapped using the Geographical Information System and open-sourced spatial data to determine distances traveled to access surgical care. RESULTS: Forty facilities were evaluated across 32 health zones; 68.9% of the provincial population was within 15 km of these facilities. Eleven facilities met a minimum World Health Organization safety score of 8; 48.1% of the population was within 15 km of corresponding facilities. The majority of children were treated by someone with specific pediatric surgery training in only 4 facilities; one facility had a trained pediatric anesthesia provider. Fifty-seven percent of the population was within 15 km of a facility with critical care and emergency medicine (EM) capabilities. There was one pediatric critical care provider and no pediatric EM providers identified within the province. Location-allocation assessment is needed to combine geographic area with potential for greatest impact and facility assessment. CONCLUSIONS: Limitations in access to surgical care in the DRC are multifactorial with poor resources, few formally trained surgical providers, and near-absent access to pediatric anesthesiologists. The study highlights the deficits in the capacity for surgical care while demonstrating a reproducible model for assessment and identification of ways to improve access to care

The state of emergency care in Democratic Republic of Congo

The Democratic Republic of Congo (DRC) is the second largest country on the African continent with a population of over 70 million. It is also a major crossroad through Africa as it borders nine countries. Unfortunately, the DRC has experienced recurrent political and social instability throughout its history and active fighting is still prevalent today. At least two decades of conflict have devastated the civilian population and collapsed healthcare infrastructure. Life expectancy is low and government expenditure on health per capita remains one of the lowest in the world. Emergency Medicine has not been established as a specialty in the DRC. While the vast majority of hospitals have emergency rooms or salle des urgences, this designation has no agreed upon format and is rarely staffed by doctors or nurses trained in emergency care. Presenting complaints include general and obstetric surgical emergencies as well as respiratory and diarrhoeal illnesses. Most patients present late, in advanced stages of disease or with extreme morbidity, so mortality is high. Epidemics include HIV, cholera, measles, meningitis and other diarrhoeal and respiratory illnesses. Lack of training, lack of equipment and fee-for-service are cited as barriers to care. Pre-hospital care is also not an established specialty. New initiatives to improve emergency care include training Congolese physicians in emergency medicine residencies and medic ranger training within national parks