SOMANZ position statement for the investigation and management of sepsis in pregnancy 2023.

BACKGROUND: The Society of Australia and New Zealand (SOMANZ) published its first sepsis in pregnancy and the postpartum period guideline in 2017 (Aust N Z J Obstet Gynaecol, 57, 2017, 540). In the intervening 6 years, maternal mortality from sepsis has remained static. AIMS: To update clinical practice with a review of the subsequent literature. In particular, to review the definition and screening tools for the diagnosis of sepsis. MATERIALS AND METHODS: A multi-disciplinary group of clinicians with experience in all aspects of the care of pregnant women analysed the clinical evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system following searches of Cochrane, Medline and EMBASE. Where there were conflicting views, the authors reviewed the topic and came to a consensus. All authors reviewed the final position statement. RESULTS: This position statement has abandoned the use of the quick Sequential Organ Failure Assessment score (qSOFA) score to diagnose sepsis due to its poor performance in clinical practice. Whilst New Zealand has a national maternity observation chart, in Australia maternity early warning system charts and vital sign cut-offs differ between states. Rapid recognition, early antimicrobials and involvement of senior staff remain essential factors to improving outcomes. CONCLUSION: Ongoing research is required to discover and validate tools to recognize and diagnose sepsis in pregnancy. Australia should follow New Zealand and have a single national maternity early warning system observation chart.

A summary of the 2023 Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) hypertension in pregnancy guideline.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines. MAIN RECOMMENDATIONS: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence-based recommendations or practice points. Evidence-based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group. CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINE: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non-pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand.

Increasing HbA1c is associated with reduced CD8+ T cell functionality in response to influenza virus in a TCR-dependent manner in individuals with diabetes mellitus.

Diabetes mellitus is on the rise globally and is a known susceptibility factor for severe influenza virus infections. However, the mechanisms by which diabetes increases the severity of an influenza virus infection are yet to be fully defined. Diabetes mellitus is hallmarked by high glucose concentrations in the blood. We hypothesized that these high glucose concentrations affect the functionality of CD8+ T cells, which play a key role eliminating virus-infected cells and have been shown to decrease influenza disease severity. To study the effect of hyperglycemia on CD8+ T cell function, we stimulated peripheral blood mononuclear cells (PBMCs) from donors with and without diabetes with influenza A virus, anti-CD3/anti-CD28-coated beads, PMA and ionomycin (PMA/I), or an influenza viral peptide pool. After stimulation, cells were assessed for functionality [as defined by expression of IFN-γ, TNF-α, macrophage inflammatory protein (MIP)-1ß, and lysosomal-associated membrane protein-1 (CD107a)] using flow cytometry. Our results showed that increasing HbA1c correlated with a reduction in TNF-α production by CD8+ T cells in response to influenza stimulation in a TCR-specific manner. This was not associated with any changes to CD8+ T cell subsets. We conclude that hyperglycemia impairs CD8+ T cell function to influenza virus infection, which may be linked with the increased risk of severe influenza in patients with diabetes.

Habitual carbohydrate intake is not correlated with circulating ß-hydroxybutyrate levels in pregnant women with overweight and obesity at 28 weeks' gestation.

AIMS/HYPOTHESIS: Pregnant women are advised to consume a minimum of 175 g per day of carbohydrate to meet maternal and fetal brain glucose requirements. This recommendation comes from a theoretical calculation of carbohydrate requirements in pregnancy, rather than from clinical data. This study aimed to determine whether fasting maternal ketone levels are associated with habitual carbohydrate intake in a subset of participants of the Study of PRobiotics IN Gestational diabetes (SPRING) randomised controlled trial. METHODS: Food frequency questionnaires on dietary intake during pregnancy were completed by pregnant women with overweight or obesity at 28 weeks' gestation (considering their intake from the beginning of pregnancy). Dietary intake from early pregnancy through to 28 weeks was analysed for macronutrient intake. At the same time, overnight fasting serum samples were obtained and analysed for metabolic parameters including serum ß-hydroxybutyrate, OGTTs, insulin and C-peptide. RESULTS: Fasting serum ß-hydroxybutyrate levels amongst 108 women (mean BMI 34.7 ± 6.3 kg/m2) ranged from 22.2 to 296.5 µmol/l. Median fasting ß-hydroxybutyrate levels were not different between women with high (median [IQR] 68.4 [49.1-109.2 µmol/l]) and low (65.4 [43.6-138.0 µmol/l]) carbohydrate intake in pregnancy. Fasting ß-hydroxybutyrate levels were not correlated with habitual carbohydrate intake (median 155 [126-189] g/day). The only metabolic parameter with which fasting ß-hydroxybutyrate levels were correlated was 1 h venous plasma glucose (ρ=0.23, p=0.03) during a 75 g OGTT. CONCLUSIONS/INTERPRETATION: Fasting serum ß-hydroxybutyrate levels are not associated with habitual carbohydrate intake at 28 weeks' gestation in pregnant women with overweight and obesity.

Pregnancy in women with cystic fibrosis and diabetes: An audit of outcomes at two tertiary obstetric hospitals in Australia in the pre-cystic fibrosis transmembrane conductance regulator modulator era.

Background: Pregnancy in women with cystic fibrosis (CF) is becoming more common. Long-term metabolic issues such as diabetes are also becoming more common and have potentially important impacts on pregnancy outcomes. This study aimed to assess the impact of diabetes on pregnancy outcomes for women with CF. Methods: We undertook a retrospective chart audit of pregnancies to women with CF at the two tertiary obstetric hospitals in Southeast Queensland associated with CF and transplant management clinics between 2006 and 2016. Results: A total of 38 pregnancies among 26 women were identified. Four women (five pregnancies) had cystic fibrosis-related diabetes (CFRD) diagnosed prior to pregnancy, and 12 women (15 pregnancies) developed gestational diabetes (GDM) complicating pregnancy. CFRD and GDM were associated with higher rates of delivery complications, prematurity, and the need for neonatal intensive care unit admission. Conclusion: Diabetes is common during pregnancy in women with CF and impacts pregnancy outcomes.

Elevated BMI reduces the humoral response to SARS-CoV-2 infection.

Objective: Class III obesity (body mass index [BMI] ≥ 40 kg m-2) significantly impairs the immune response to SARS-CoV-2 vaccination. However, the effect of an elevated BMI (≥ 25 kg m-2) on humoral immunity to SARS-CoV-2 infection and COVID-19 vaccination remains unclear. Methods: We collected blood samples from people who recovered from SARS-CoV-2 infection approximately 3 and 13 months of post-infection (noting that these individuals were not exposed to SARS-CoV-2 or vaccinated in the interim). We also collected blood samples from people approximately 5 months of post-second dose COVID-19 vaccination (the majority of whom did not have a prior SARS-CoV-2 infection). We measured their humoral responses to SARS-CoV-2, grouping individuals based on a BMI greater or less than 25 kg m-2. Results: Here, we show that an increased BMI (≥ 25 kg m-2), when accounting for age and sex differences, is associated with reduced antibody responses after SARS-CoV-2 infection. At 3 months of post-infection, an elevated BMI was associated with reduced antibody titres. At 13 months of post-infection, an elevated BMI was associated with reduced antibody avidity and a reduced percentage of spike-positive B cells. In contrast, no significant association was noted between a BMI ≥ 25 kg m-2 and humoral immunity to SARS-CoV-2 at 5 months of post-secondary vaccination. Conclusions: Taken together, these data showed that elevated BMI is associated with an impaired humoral immune response to SARS-CoV-2 infection. The impairment of infection-induced immunity in individuals with a BMI ≥ 25 kg m-2 suggests an added impetus for vaccination rather than relying on infection-induced immunity.

Women with gestational diabetes mellitus, controlled for plasma glucose level, exhibit maternal and fetal dyslipidaemia that may warrant treatment.

AIMS: To compare maternal and fetal cord plasma and lipoprotein triglyceride (TG) concentrations in women with Gestational Diabetes Mellitus (GDM), with hyperglycaemia and hypertriglyceridaemia, and healthy women. METHODS: Fasted maternal blood at 28.6 ± 3.4 (T1) and 36.2 ± 1.0 (T2) [mean ± S.D] weeks of gestation, and cord blood were collected. Plasma lipoprotein fractions underwent compositional analysis. RESULTS: Plasma glucose did not differ between GDM and healthy women. T1 maternal plasma TG (2.60 ± 0.89 mmol/l versus 1.71 ± 0.69 mmol/l) and plasma apolipoprotein B (1.30 ± 0.48 g/l versus 0.75 ± 0.40 g/l) were higher in GDM compared to healthy. Maternal plasma TG increased over gestation in both groups. T1 plasma VLDL total protein (38 ± 15 mg/dl versus 25 ± 11 mg/dl), total cholesterol (TC) (30 ± 14 mg/dl versus 16 ± 13 mg/dl) and phospholipid (PL) (43 ± 17 mg/dl versus 26 ± 16 mg/dl) were higher in GDM than healthy, and similarly for IDL, suggesting increased lipoprotein particle number. T1 VLDL-TG enrichment was higher in healthy and increased over gestation in GDM women but decreased in healthy. IDL-TG enrichment (TG/TC) increased over gestation in women with GDM and decreased in healthy. Cord blood VLDL, IDL and LDL from GDM had a two-fold higher TG enrichment than healthy pregnancy. CONCLUSION: Increased maternal lipoprotein number, but not TG enrichment, in GDM mothers may explain TG enrichment of cord lipoproteins.

Emotional well-being and HbA1c following the implementation of the Diabetes Psychosocial Assessment Tool (DPAT) in young adults with type 1 diabetes (T1DM): An observational study.

AIMS: This observational study evaluated the implementation of the Diabetes Psychosocial Assessment Tool (DPAT), assessing emotional well-being of young adults with type 1 diabetes (T1DM) and the clinical congruency between DPAT-recommended and specialist-led referrals. METHODS: Young adults with T1DM attending the clinic completed the DPAT on two occasions. The DPAT includes the PAID (diabetes distress), PHQ-4 (depression/anxiety) and WHO-5 (general well-being), a diabetes health audit and a referral pathway to (allied) health professionals. Demographic and clinical information was retrieved from medical records. Data was analyzed using descriptive statistics and generalized estimating equations. RESULTS: 115 people with T1DM, aged 16-25 years, were included in the analysis. Symptoms of moderate-severe diabetes distress were present in 29 (25%) participants, symptoms of depression/anxiety and impaired well-being in 21 (19%) and 26 (23%) participants, respectively. The odds of depression/anxiety symptoms was lower at the second timepoint compared to the first timepoint (OR 0.55, 95% CI 0.32-0.96, p = 0.03). The odds of moderate-severe diabetes distress tended to be lower. No change was observed in general well-being or HbA1c. There was moderate concordance between DPAT and clinician referrals to psychologists (81%) and dieticians (70%). CONCLUSIONS: Using the DPAT facilitates the conversation about emotional well-being during routine consultation and follow-up.

Non-conventional laryngeal malignancies: a multicentre review of management and outcomes.

PURPOSE: Non-conventional laryngeal malignancies (NSCC) often have limited published data to guide management despite individual histopathological subtypes often exhibiting heterogeneous behaviour, characteristics, and treatment responses compared to laryngeal squamous cell carcinoma (SCC). This study aimed to compare oncological outcomes with SCC, specifically disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS). Secondary objectives were to compare treatment differences and perform a state of the art review. METHODS: This was a multicentre retrospective cohort study at four tertiary head and neck centres. Survival outcomes between NSCC and SCC patients were analysed with Kaplan-Meier curves and compared by log rank testing. Univariate Cox regression analysis was performed to predict survival by histopathological subgroup, T-stage, N-stage and M-stage. RESULTS: There were no significant differences in 3-year DFS (p = 0.499), DSS (p = 0.329), OS (p = 0.360) or Kaplan Meier survival curves (DSS/OS) between SCC and overall NSCC groups. However, univariate Cox regression analysis identified "rare" histopathologies (mostly small cell carcinoma) to be predictive of less favourable OS (p = 0.035) but this result was not observed for other NSCC histopathological subgroups. N-stage (p = 0.027) and M-stage (p = 0.048) also predicted OS for NSCC malignancies. Significant differences in treatment modalities were identified with treatment of NSCC typically involving surgical resection and SCC often managed non-surgically (e.g., primary radiotherapy). CONCLUSIONS: Although overall NSCC is managed differently compared to SCC, there do not appear to be differences in survival outcomes between these groups. N-stage and M-stage appear to be more predictive of OS than histopathology than many NSCC subtypes.

Continuous Glucose Monitoring in Young Adults With Type 1 Diabetes: Impact on Hypoglycemia Confidence and Fear.

Background: Fear of hypoglycemia in people with type 1 diabetes has a detrimental effect on glycemic control and quality of life. The association between continuous glucose monitoring (CGM) and hypoglycemia confidence and fear has not previously been assessed in the young adult population. Methods: This was a prospective cohort study using questionnaires to assess the impact of CGM on hypoglycemia confidence (using the Hypoglycemia Confidence Scale [HCS]) and hypoglycemia fear (using the Hypoglycemia Fear Survey II [HFS]) in 40 young adults with a preexisting diagnosis of type 1 diabetes. Results: Scores on the HCS were greater at baseline for those with a longer duration of diabetes. Participants with higher general anxiety scores on the Generalized Anxiety Disorder 7-item scale had higher hypoglycemia fear at baseline (total score and worry component, but not behavior component of the HFS). Between baseline and follow-up, HCS scores increased on average by 0.2 (95% CI 0.1-0.4, P = 0.01) on a scale of 1-4. HFS scores decreased by 1.8 (95% CI -3.0 to -0.5, P = 0.006) on a scale of 0-24 for the worry component and by 2.5 (95% CI -4.4 to -0.6, P = 0.01) on a scale of 0-44 for total (worry + behavior components). At follow up, 83% of participants planned to continue using CGM all or most of the time. There was a very high self-reported effect of CGM on life with diabetes (median 8.0 [interquartile range 6.5-10.0], where 10 indicated a very big difference). Conclusion: Hypoglycemia confidence and fear improve with CGM use in young adults.

Effect of asthma management with exhaled nitric oxide versus usual care on perinatal outcomes.

INTRODUCTION: Asthma exacerbations in pregnancy are associated with adverse perinatal outcomes. We aimed to determine whether fractional exhaled nitric oxide (F ENO)-based asthma management improves perinatal outcomes compared to usual care. METHODS: The Breathing for Life Trial was a multicentre, parallel-group, randomised controlled trial conducted in six hospital antenatal clinics, which compared asthma management guided by F ENO (adjustment of asthma treatment according to exhaled nitric oxide and symptoms each 6-12 weeks) to usual care (no treatment adjustment as part of the trial). The primary outcome was a composite of adverse perinatal events (preterm birth, small for gestational age (SGA), perinatal mortality or neonatal hospitalisation) assessed using hospital records. Secondary outcomes included maternal asthma exacerbations. Concealed random allocation, stratified by study site and self-reported smoking status was used, with blinded outcome assessment and statistical analysis (intention to treat). RESULTS: Pregnant women with current asthma were recruited; 599 to the control group (608 infants) and 601 to the intervention (615 infants). There were no significant group differences for the primary composite perinatal outcome (152 (25.6%) out of 594 control, 177 (29.4%) out of 603 intervention; OR 1.21, 95% CI 0.94-1.56; p=0.15), preterm birth (OR 1.14, 95% CI 0.78-1.68), SGA (OR 1.06, 95% CI 0.78-1.68), perinatal mortality (OR 3.62, 95% CI 0.80-16.5), neonatal hospitalisation (OR 1.24, 95% CI 0.89-1.72) or maternal asthma exacerbations requiring hospital admission or emergency department presentation (OR 1.19, 95% CI 0.69-2.05). CONCLUSION: F ENO-guided asthma pharmacotherapy delivered by a nurse or midwife in the antenatal clinic setting did not improve perinatal outcomes.

Exploring the diets of mothers and their partners during pregnancy: Findings from the Queensland Family Cohort pilot study.

AIM: Modifiable behaviours during the first 1000 days of life influence developmental trajectories of adult chronic diseases. Despite this, sub-optimal dietary intakes during pregnancy and excessive gestational weight gain are common. Very little is known about partners' dietary patterns and the influence on women's pregnancy dietary patterns. We aimed to examine dietary intake during pregnancy among women and their partners, and gestational weight gain patterns in the Queensland Family Cohort pilot study. METHODS: The Queensland Family Cohort is a prospective, observational study piloted at a Brisbane (Australia) tertiary maternity hospital from 2018 to 2021. Participant characteristics, weight gain, dietary and nutrient intake were assessed. RESULTS: Data were available for 194 pregnant women and their partners. Poor alignment with Australian Guide to Healthy Eating recommendations was observed. Highest alignment was for fruit (40% women) and meat/alternatives (38% partners) and lowest for breads/cereals (<1% women) and milk/alternatives (13% partners). Fewer women (4.4%-60.3%) than their partners (5.4%-92.3%) met guidelines for all micronutrient intakes from food alone, particularly folic acid, iodine, and iron. Women were more likely to meet daily recommendations for fruit, vegetables, dairy, bread/cereals, and meat/alternatives when their partners also met recommendations. Women with a higher pre-pregnancy body mass index were more likely to gain above recommended weight gain ranges. CONCLUSIONS: In this contemporary cohort of pregnant women and their partners, sub-optimal dietary patterns and deficits in some nutrients were common. There is an urgent need for evidence-informed public health policy and programs to improve diet quality during pregnancy due to intergenerational effects.

Reduced Abundance of Nitrate-Reducing Bacteria in the Oral Microbiota of Women with Future Preeclampsia.

The oral microbiota can contribute to the regulation of blood pressure by increasing the availability of nitric oxide through the reduction of nitrate to nitrite, which can be converted into nitric oxide in the stomach and then enter the circulation. It is unclear if the composition of the oral microbiota is different between women who do and do not develop preeclampsia. This study aimed to compare the composition of the buccal microbiota just prior to the development of symptoms at 36 weeks gestation in 12 women who developed late-onset preeclampsia and 24 matched women who remained normotensive throughout pregnancy by 16S rRNA gene amplicon sequencing. The abundance of the nitrate-reducing Veillonella spp V. parvula and V. dispar and a subunit of nitrate reductase narH was compared using real-time PCR. The abundance of bacteria was correlated with maternal blood pressure and dietary intake of nitrate-containing vegetables. The results showed that the abundance of nitrate-reducing bacteria including Veillonella, specifically V. parvula, and Prevotella was reduced in women who developed preeclampsia. Veillonella but not Prevotella abundance was negatively correlated with maternal blood pressure. The dietary intake of nitrate-containing vegetables did not differ between the groups and was not correlated with the abundance of Veillonella. There was no difference in the abundance of the nitrate reductase subunit narH between the groups. These results suggest that the abundance of nitrate-reducing bacteria is reduced in the oral microbiota of women who later develop preeclampsia, indicating a potential pathway for prevention.

The impact of a modified carbohydrate formula, and its constituents, on glycaemic control and inflammatory markers: A nested mechanistic sub-study.

BACKGROUND: Hyperglycaemia occurs frequently in the critically ill. Dietary intake of advanced glycation end-products (AGEs), specifically Nε-(carboxymethyl)lysine (CML), may exacerbate hyperglycaemia through perturbation of insulin sensitivity. The present study aimed to determine whether the use of nutritional formulae, with varying AGE loads, affects the amount of insulin administered and inflammation. METHODS: Exclusively tube fed patients (n = 35) were randomised to receive Nutrison Protein Plus Multifibre®, Diason® or Glucerna Select®. Insulin administration was standardised according to protocol based on blood glucose (<10 mmol L-1 ). Samples were obtained at randomisation and 48 h later. AGEs in nutritional formula, plasma and urine were measured using mass spectrometry. Plasma inflammatory markers were measured using an enzyme-linked immunosorbent assay and multiplex bead-based assays. RESULTS: AGE concentrations of CML in nutritional formulae were greatest with delivery of Nutrison Protein Plus® (mean [SD]; 6335 pmol mol-1 [2436]) compared to Diason® (4836 pmol mol-1 [1849]) and Glucerna Select® (4493 pmol mol-1 [1829 pmol mol-1 ]) despite patients receiving similar amounts of energy (median [interquartile range]; 12 MJ [8.2-13.7 MJ], 11.5 MJ [8.3-14.5 MJ], 11.5 MJ [8.3-14.5 MJ]). More insulin was administered with Nutrison Protein Plus® (2.47 units h-1 [95% confidence interval (CI) = 1.57-3.37 units h-1 ]) compared to Diason® (1.06 units h-1 [95% CI = 0.24-1.89 units h-1 ]) or Glucerna Select® (1.11 units h-1 [95% CI = 0.25-1.97 units h-1 ]; p = 0.04). Blood glucose concentrations were similar. There were associations between greater insulin administration and reductions in circulating interleukin-6 (r = -0.46, p < 0.01), tumour necrosis factor-α (r = -0.44, p < 0.05), high sensitivity C-reactive protein (r = -0.42, p < 0.05) and soluble receptor for advanced glycation end-products (r = -0.45, p < 0.01) concentrations. CONCLUSIONS: The administration of greater AGE load in nutritional formula potentially increases the amount of insulin required to maintain blood glucose within a normal range during critical illness. There was an inverse relationship between exogenous insulin and plasma inflammatory markers.

Consumption of a Low Carbohydrate Diet in Overweight or Obese Pregnant Women Is Associated with Longer Gestation of Pregnancy.

Studies of obstetric outcomes in women consuming low-carbohydrate diets have reported conflicting results. Most studies have defined low-carbohydrate diets by the percentage that carbohydrates contribute to overall energy intake, rather than by an absolute amount in grams per day (g/d). We hypothesised that a low absolute carbohydrate diet affects obstetric outcomes differently than a low percentage carbohydrate diet. Dietary data were collected from overweight or obese women in the Study of Probiotic IN Gestational diabetes at 16- and 28-weeks' gestation. Obstetric outcomes were compared between women whose carbohydrate intake was in the lowest quintile vs quintiles 2-5. Mean gestation was increased in women whose absolute carbohydrate intake was in the lowest quintile at 16 and at both 16- and 28-weeks' gestation compared with all other women (16: 39.7 vs. 39.1 weeks, p = 0.008; 16 and 28: 39.8 vs. 39.1, p = 0.005). In linear regression analysis, a low absolute carbohydrate intake at 16 and at 28 weeks' gestation was associated with increased gestation at delivery (16: p = 0.04, adjusted R2 = 0.15, 28: p = 0.04, adjusted R2 = 0.17). The coefficient of beta at 16 weeks' gestation was 0.50 (95% CI 0.03-0.98) and at 28 weeks' gestation was 0.51 (95%CI 0.03-0.99) meaning that consumption of a low absolute carbohydrate diet accounted for an extra 3.5 days in gestational age. This finding was not seen in women whose percentage carbohydrate intake was in the lowest quintile. Low-carbohydrate consumption in pregnancy is associated with increased gestational age at delivery.

Update on pulmonary embolism in pregnancy and post-partum: The Society of Obstetric Medicine of Australia and New Zealand Position Statement on Pulmonary Embolism in Pregnancy and Post-partum.

In this clinical review we highlight aspects of the diagnosis and management of pulmonary embolism (PE) in pregnancy and post-partum and how this may impact on antenatal and postnatal management. Investigation for PE in pregnancy is challenging and includes appropriate patient selection and knowledge of the risks and benefits of pulmonary imaging modalities. The complete Society of Obstetric Medicine of Australia and New Zealand Position Statement on Pulmonary Embolism in Pregnancy and Post-Partum comprehensively reviews all aspects of diagnosis, investigation and management and is accessible at https://www.somanz.org/guidelines.asp. It includes a summary of all recommendations and a guide to developing a management plan for birth in women on anticoagulation.

T-Cell Expression and Release of Kidney Injury Molecule-1 in Response to Glucose Variations Initiates Kidney Injury in Early Diabetes.

Half of the mortality in diabetes is seen in individuals <50 years of age and commonly predicted by the early onset of diabetic kidney disease (DKD). In type 1 diabetes, increased urinary albumin-to-creatinine ratio (uACR) during adolescence defines this risk, but the pathological factors responsible remain unknown. We postulated that early in diabetes, glucose variations contribute to kidney injury molecule-1 (KIM-1) release from circulating T cells, elevating uACR and DKD risk. DKD risk was assigned in youth with type 1 diabetes (n = 100; 20.0 ± 2.8 years; males/females, 54:46; HbA1c 66.1 [12.3] mmol/mol; diabetes duration 10.7 ± 5.2 years; and BMI 24.5 [5.3] kg/m2) and 10-year historical uACR, HbA1c, and random blood glucose concentrations collected retrospectively. Glucose fluctuations in the absence of diabetes were also compared with streptozotocin diabetes in apolipoprotein E -/- mice. Kidney biopsies were used to examine infiltration of KIM-1-expressing T cells in DKD and compared with other chronic kidney disease. Individuals at high risk for DKD had persistent elevations in uACR defined by area under the curve (AUC; uACRAUC0-10yrs, 29.7 ± 8.8 vs. 4.5 ± 0.5; P < 0.01 vs. low risk) and early kidney dysfunction, including ∼8.3 mL/min/1.73 m2 higher estimated glomerular filtration rates (modified Schwartz equation; Padj < 0.031 vs. low risk) and plasma KIM-1 concentrations (∼15% higher vs. low risk; P < 0.034). High-risk individuals had greater glycemic variability and increased peripheral blood T-cell KIM-1 expression, particularly on CD8+ T cells. These findings were confirmed in a murine model of glycemic variability both in the presence and absence of diabetes. KIM-1+ T cells were also infiltrating kidney biopsies from individuals with DKD. Healthy primary human proximal tubule epithelial cells exposed to plasma from high-risk youth with diabetes showed elevated collagen IV and sodium-glucose cotransporter 2 expression, alleviated with KIM-1 blockade. Taken together, these studies suggest that glycemic variations confer risk for DKD in diabetes via increased CD8+ T-cell production of KIM-1.

Systematic Review: Diabetes Family Conflict in Young People With Type 1 Diabetes.

OBJECTIVE: To investigate the relationships between diabetes-specific family conflict and health outcomes of young people with type 1 diabetes (T1D). METHODS: A systematic review was performed according to the PRISMA statement (registration number: CRD42020164988). PubMed, Embase, PsycNET, reference lists of included studies, and other relevant reviews were searched (1990-2020). Two independent reviewers screened titles, abstracts, and full-texts. Studies were included if they sampled young people with T1D (mean age between 14 and 25 years) and examined the relationship between diabetes-specific family conflict and the following outcomes: glycated hemoglobin (HbA1c), treatment adherence, blood glucose monitoring, depression, anxiety, quality of life, and/or well-being. RESULTS: A total of 20 studies met the predetermined inclusion criteria. Greater diabetes-specific family conflict was significantly related to higher HbA1c values in 17 studies. Seven studies reported a significant association between greater diabetes family conflict and suboptimal treatment adherence and/or less frequent blood glucose monitoring. However, significant relationships between conflict and HbA1c and/or treatment adherence were not found in four studies. Seven studies in total reported that greater diabetes family conflict was significantly related to poorer quality of life or well-being and greater depressive and/or anxiety symptoms in young people. CONCLUSIONS: Diabetes-specific family conflict is associated with some adverse health outcomes for young people with T1D. However, more longitudinal studies of young people aged older than 16 years are needed. Screening for and addressing diabetes-specific family conflict is recommended, given the growing number of studies linking family conflict to various adverse health outcomes in young people with T1D.

The role of T-cell immunity in COVID-19 severity amongst people living with type II diabetes.

The COVID-19 pandemic has highlighted the vulnerability of people with diabetes mellitus (DM) to respiratory viral infections. Despite the short history of COVID-19, various studies have shown that patients with DM are more likely to have increased hospitalisation and mortality rates as compared to patients without. At present, the mechanisms underlying this susceptibility are unclear. However, prior studies show that the course of COVID-19 disease is linked to the efficacy of the host's T-cell responses. Healthy individuals who can elicit a robust T-cell response are more likely to limit the severity of COVID-19. Here, we investigate the hypothesis that an impaired T-cell response in patients with type 2 diabetes mellitus (T2DM) drives the severity of COVID-19 in this patient population. While there is currently a limited amount of information that specifically addresses T-cell responses in COVID-19 patients with T2DM, there is a wealth of evidence from other infectious diseases that T-cell immunity is impaired in patients with T2DM. The reasons for this are likely multifactorial, including the presence of hyperglycaemia, glycaemic variability and metformin use. This review emphasises the need for further research into T-cell responses of COVID-19 patients with T2DM in order to better inform our response to COVID-19 and future disease outbreaks.