Geospatial mapping and data linkage uncovers variability in outcomes of foot disease according to multiple deprivation: a population cohort study of people with diabetes

Aims/hypothesis: Our aim was to investigate the geospatial distribution of diabetic foot ulceration (DFU), lower extremity amputation (LEA) and mortality rates in people with diabetes in small geographical areas with varying levels of multiple deprivation. Methods: We undertook a population cohort study to extract the health records of 112,231 people with diabetes from the Scottish Care Information – Diabetes Collaboration (SCI-Diabetes) database. We linked this to health records to identify death, LEA and DFU events. These events were geospatially mapped using multiple deprivation maps for the geographical area of National Health Service (NHS) Greater Glasgow and Clyde. Tests of spatial autocorrelation and association were conducted to evaluate geographical variation and patterning, and the association between prevalence-adjusted outcome rates and multiple deprivation by quintile. Results: Within our health board region, people with diabetes had crude prevalence-adjusted rates for DFU of 4.6% and for LEA of 1.3%, and an incidence rate of mortality preceded by either a DFU or LEA of 10.5 per 10,000 per year. Spatial autocorrelation identified statistically significant hot spot (high prevalence) and cold spot (low prevalence) clusters for all outcomes. Small-area maps effectively displayed near neighbour clustering across the health board geography. Disproportionately high numbers of hot spots within the most deprived quintile for DFU (p < 0.001), LEA (p < 0.001) and mortality (p < 0.001) rates were found. Conversely, a disproportionately higher number of cold spots was found within the least deprived quintile for LEA (p < 0.001). Conclusions/interpretation: In people with diabetes, DFU, LEA and mortality rates are associated with multiple deprivation and form geographical neighbourhood clusters

Antenatal Magnesium Sulfate and Preeclampsia Differentially Affect Neonatal Cerebral Oxygenation

Introduction: Magnesium sulfate (MgSO4) is frequently administered for maternal and fetal neuroprotection in preeclampsia (PE) and imminent preterm birth, respectively. Objective: To assess whether MgSO4 affects neonatal cerebral oxygenation, blood flow, and cerebral autoregulation (CAR) during the first postnatal days independently from PE. Methods: 148 neonates 0.5) was determined. Linear mixed models were applied. Results: MgSO4 exposure was recorded in 77 neonates. Twenty-nine neonates were born following PE. MgSO4 independently lowered cFTOE (B: -0.026, 95% CI: -0.050 to 0.002, p < 0.05) but did not affect PSV and RI. PE was associated with a lower cFTOE (B: -0.041, 95% CI: -0.067 to -0.015, p < 0.05) and a tendency towards both lower PSV (B: -4.285, 95% CI: -9.067 to 0.497, p < 0.1) and more impaired CAR (B: 4.042, 95% CI: -0.028 to 8.112, p < 0.1), which seemed to be strongly mediated by fetal brain sparing. MgSO4 did not alter CAR. Conclusions: In contrast to fetal brain sparing in PE, MgSO4 seems to lower cFTOE by lowering cerebral oxygen demands in preterm neonates without affecting the cerebrovasculature

Decidual memory T‐cell subsets and memory T‐cell stimulatory cytokines in early‐ and late‐onset preeclampsia

Problem: Preeclampsia is a major cause of fetal and maternal mortality and morbidity. Disturbed fetal-maternal immune tolerance, and therewith memory T cells, might be involved in its etiology. This study aims to give insight into memory T-cell populations and its associated cytokines in the decidual layers in early-onset preeclampsia (EO-PE) and late-onset preeclampsia (LO-PE). Method of Study: Lymphocytes were isolated from the decidua parietalis and basalis from EO-PE (n = 6), LO-PE (n = 8) and healthy (n = 15) pregnancies. CD4+ and CD8+ central- (CCR7+), effector- (CCR7−), tissue resident- (CD103+), and regulatory- (Foxp3+) memory cell (CD45RO+) populations and their activation status (CD69+) were analyzed using flow cytometry. qRT-PCR analysis was performed on decidua parietalis and basalis biopsies to detect mRNA expression of interferon-gamma, interleukin-1B, IL2, IL6, IL7, IL8, IL10, IL15, and IL23. Results: CD4+ central-memory (CM) cell proportions were lower in the decidua parietalis in LO-PE (P <.0001) and EO-PE (P <.01) compared to healthy pregnancies. CD8+ memory (P <.05) and CD8+ CM (P <.01) cell proportions were also lower in the decidua parietalis in EO-PE compared to healthy pregnancies. This was accompanied by higher IL15 (P <.05) and IL23 (P <.05) and lower IL7 (P <.05) mRNA expression in decidua basalis biopsies from EO-PE compared to healthy pregnancies, analyzed by qPCR. Conclusion: In conclusion, decidual memory T-cell proportions, their activation status, and associated cytokines are altered in preeclampsia and might therefore be involved in fetal-maternal immune tolerance and the pathophysiology of preeclampsia

Evaluation of CO2-doped blends in single-stage with IHX and parallel compression refrigeration architectures

CO2 is the standard for medium to large-sized commercial applications, as it combines security and low environmental impact. However, it requires the use of advanced and complex cycles. Recently, CO2-doping (the addition of a small quantity of another fluid) has attracted scientific attention, as when CO2 is mixed with fluids with higher critical temperatures, the optimum operation moves to subcritical, providing COP increments in relation to pure-CO2 operation. This work, from a theoretical perspective, evaluates CO2-doping with the fluids R-152a, R-1234yf, R-1234ze(E) and R-1233zd(E) considering the two most used CO2 cycles: the base cycle with an internal heat exchanger (IHX) and the cycle with parallel compression (PC), fractionation taking place. The work analyses the COP improvements for an evaporating level of -10°C and from 10 to 40°C of environment temperature. Predicted maximum COP increments reach up to 5.8% for the IHX cycle and 10.0% for the PC cycle

Dysregulation of Complement Activation and Placental Dysfunction:A Potential Target to Treat Preeclampsia?

Preeclampsia is one of the leading causes of maternal and neonatal mortality and morbidity worldwide, affecting 2-8% of all pregnancies. Studies suggest a link between complement activation and preeclampsia. The complement system plays an essential role in the innate immunity, leading to opsonization, inflammation, and elimination of potential pathogens. The complement system also provides a link between innate and adaptive immunity and clearance of immune complexes and apoptotic cells. During pregnancy there is increased activity of the complement system systemically. However, locally at the placenta, complement inhibition is crucial for the maintenance of a normal pregnancy. Inappropriate or excessive activation of the complement system at the placenta is likely involved in placental dysfunction, and is in turn associated with pregnancy complications like preeclampsia. Therefore, modulation of the complement system could be a potential therapeutic target to prevent pregnancy complications such as preeclampsia. This review, based on a systematic literature search, gives an overview of the complement system and its activation locally in the placenta and systemically during healthy pregnancies and during complicated pregnancies, with a focus on preeclampsia. Furthermore, this review describes results of animal and human studies with a focus on the complement system in pregnancy, and the role of the complement system in placental dysfunction. Various clinical and animal studies provide evidence that dysregulation of the complement system is associated with placental dysfunction and therefore with preeclampsia. Several drugs are used for prevention and treatment of preeclampsia in humans and animal models, and some of these drugs work through complement modulation. Therefore, this review further discusses these studies examining pharmaceutical interventions as treatment for preeclampsia. These observations will help direct research to generate new target options for prevention and treatment of preeclampsia, which include direct and indirect modulation of the complement system

Efficacy of at home monitoring of foot temperature for risk reduction of diabetes-related foot ulcer: A meta-analysis

Aims: To perform an updated systematic review of randomised controlled trials examining the efficacy of at-home foot temperature monitoring in reducing the risk of a diabetes-related foot ulcer (DFU). Methods: Systematic review performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Risk-of-bias was assessed using version 2 of the Cochrane risk-of-bias tool. Meta-analyses were performed using random effect models. Leave-one-out sensitivity analyses and a sub-analysis excluding trials considered at high risk-of-bias assessed the consistency of the findings. The certainty of the evidence was assessed with GRADE. Results: Five randomised controlled trials involving 772 participants meeting the International Working Group on the Diabetic Foot (IWGDF) risk category 2 or 3 were included. All trials reported instructing participants to measure skin temperature at-home at six or more sites on each foot using a hand-held infra-red thermometer at least daily and reduce ambulatory activity in response to hotspots (temperature differences >2.2°C on two consecutive days between similar locations in both feet). One, one, and three trials were considered at low, moderate and high risk-of-bias, respectively. Participants allocated to at-home foot temperature monitoring had a reduced risk of developing a DFU (relative risk 0.51, 95% CI 0.31–0.84) compared to controls. Sensitivity and sub-analyses suggested that the significance of this finding was consistent. The GRADE assessment suggested a low degree of certainty in the finding. Conclusions: At-home daily foot temperature monitoring and reduction of ambulatory activity in response to hotspots reduce the risk of a DFU in moderate or high risk people with a low level of certainty

Preeclampsia is Associated with lower Percentages of Regulatory T Cells in Maternal Blood

Objective: Immunological mechanisms are involved in the pathophysiology of preeclampsia. During pregnancy there is an increase in regulatory T (Treg) cells, which has an important role in regulating tolerance to the immunologically distinct fetus. We hypothesised that percentages of Treg cells are decreased in preeclamptic patients. Methods: Peripheral blood was obtained from 26 healthy pregnant controls and 18 preeclamptic patients. Treg cells were measured using flow-cytometry. Results: Women with pregnancies complicated by preeclampsia had significantly lower percentages of CD4(+)FOXP3(+) Treg cells. Conclusion: We conclude that a deficiency of regulatory T cells may play a role in the pathophysiology of preeclampsia