Correlation between cognitive assessment scores and circulating cerebral biomarkers in women with pre-eclampsia and eclampsia.

OBJECTIVES: The cerebral injury biomarkers neurofilament light chain (NfL) and tau and the glial activation biomarker glial fibrillary acidic protein (GFAP) may reflect neurological injury in pre-eclampsia. We assessed if there was a correlation between cognitive function assessment scores and plasma concentrations of these biomarkers in pre-eclampsia. STUDY DESIGN: Women with eclampsia, pre-eclampsia and normotensive pregnancies from the South African PROVE biobank were included. Blood samples were taken at inclusion. The Montreal Cognitive Assessment was performed after delivery at the time of discharge. The correlation between cognitive assessment scores and plasma concentrations of cerebral biomarkers was analysed using Spearman correlation adjusted for time from eclamptic seizure. MAIN OUTCOME MEASURES: We included 49 women with eclampsia, 16 women with pre-eclampsia complicated by pulmonary oedema, 22 women with pre-eclampsia without pulmonary oedema, HELLP or neurological complications and 18 women with normotensive pregnancies. RESULTS: There was a correlation between impaired cognitive function and increased plasma concentrations of NfL in women with eclampsia and women with pre-eclampsia and pulmonary oedema (r = -0.37, p = 0.009 and r = -0.56, p = 0.025 respectively). No correlation between impaired cognitive function and NfL in pre-eclampsia cases without pulmonary oedema, HELLP or neurological complications or normotensive pregnancies was found. No correlation with cognitive impairment was found in any groups for tau or GFAP. CONCLUSIONS: We found a correlation between impaired cognitive function assessment and plasma NfL concentrations in women with eclampsia and pre-eclampsia complicated by pulmonary oedema. These findings suggest that acute neuroaxonal injury may cause or contribute to cognitive impairment in these women.

Cerebral biomarkers in neurologic complications of preeclampsia.

BACKGROUND: There is no tool to accurately predict who is at risk of developing neurologic complications of preeclampsia, and there is no objective method to determine disease severity. OBJECTIVE: We assessed whether plasma concentrations of the cerebral biomarkers neurofilament light, tau, and glial fibrillary acidic protein could reflect disease severity in several phenotypes of preeclampsia. Furthermore, we compared the cerebral biomarkers with the angiogenic biomarkers soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin. STUDY DESIGN: In this observational study, we included women from the South African Preeclampsia Obstetric Adverse Events biobank. Plasma samples taken at diagnosis (preeclampsia cases) or admission for delivery (normotensive controls) were analyzed for concentrations of neurofilament light, tau, glial fibrillary acidic protein, placental growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin. The cerebrospinal fluid concentrations of inflammatory markers and albumin were analyzed in a subgroup of 15 women. Analyses were adjusted for gestational age, time from seizures and delivery to sampling, maternal age, and parity. RESULTS: Compared with 28 women with normotensive pregnancies, 146 women with preeclampsia demonstrated 2.18-fold higher plasma concentrations of neurofilament light (95% confidence interval, 1.64-2.88), 2.17-fold higher tau (95% confidence interval, 1.49-3.16), and 2.77-fold higher glial fibrillary acidic protein (95% confidence interval, 2.06-3.72). Overall, 72 women with neurologic complications (eclampsia, cortical blindness, and stroke) demonstrated increased plasma concentrations of tau (2.99-fold higher; 95% confidence interval, 1.92-4.65) and glial fibrillary acidic protein (3.22-fold higher; 95% confidence interval, 2.06-5.02) compared with women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications (n=31). Moreover, angiogenic markers were higher, but to a lesser extent. Women with hemolysis, elevated liver enzymes, and low platelet count (n=20) demonstrated increased plasma concentrations of neurofilament light (1.64-fold higher; 95% confidence interval, 1.06-2.55), tau (4.44-fold higher; 95% confidence interval, 1.85-10.66), and glial fibrillary acidic protein (1.82-fold higher; 95% confidence interval, 1.32-2.50) compared with women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications. There was no difference shown in the angiogenic biomarkers. There was no difference between 23 women with preeclampsia complicated by pulmonary edema and women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications for any of the biomarkers. Plasma concentrations of tau and glial fibrillary acidic protein were increased in women with several neurologic complications compared with women with eclampsia only. CONCLUSION: Plasma neurofilament light, glial fibrillary acidic, and tau were candidate biomarkers for the diagnosis and possibly prediction of cerebral complications of preeclampsia.

May Measurement Month 2019: an analysis of blood pressure screening results from the United Kingdom and Republic of Ireland.

In the UK, heart and circulatory diseases account for 29% of all deaths (14% through coronary heart disease and 8% through stroke). In 2015, the prevalence of hypertension was 20% in the UK and 23% in the Republic of Ireland. In 2019, 14% of people registered with a UK general practice had hypertension and yet it was the attributable risk factor for around half of all deaths from coronary heart disease or stroke. We participated in May Measurement Month 2019 to increase awareness of blood pressure (BP) measurement, and to identify the proportion of undiagnosed hypertension and degree of uncontrolled hypertension in the community. The 2019 campaign set up screening sites within the community at places of worship, supermarkets, GP surgeries, workplaces, charity events, community pharmacies, gyms, and various other public places. We screened 10194 participants (mean age 51 ± 18 years, 60% women) and found that 1013 (9.9%) were on antihypertensive treatment, while 3408 (33.4%) had hypertension. Of the 3408 participants with hypertension, only 33.5% were aware of their condition despite 98.8% having previous BP measurements. In those on antihypertensive medication, only 38.2% had controlled BP (<140 and <90 mmHg). Our UK and Republic of Ireland data demonstrate concerning levels of undiagnosed hypertension and sub-optimal BP control in many individuals with a diagnosis. This evidence supports a critical need for better systematic community and primary care screening initiatives.

Point-of-care echocardiographic screening for left-sided valve heart disease: high yield and affordable cost in an elderly cohort recruited in primary practice.

BACKGROUND: Data about the epidemiology of valvular heart disease (VHD) in the elderly is scarce. Hand-held ultrasound devices (HUDs) enable point-of-care ultrasound scanning (POCUS) but their use in an elderly population has not been reported for VHD screening in primary practice. METHODS: One hundred consecutive subjects aged >70 years without a VHD diagnosis had 2D and colour Doppler POCUS by an accredited sonographer, using a contemporary HUD (Vscan), in a primary practice setting. Patients with left-sided valve pathology identified by Vscan were referred for formal echo in the local tertiary cardiac centre. RESULTS: Mean age (s.d.) was 79.08 (3.74) years (72-92 years); 61 female. By Vscan, we found five patients with ≥moderate aortic stenosis (AS), eight with ≥moderate mitral regurgitation (MR) and none with ≥moderate aortic regurgitation. In the AS and MR groups each, one patient had valve intervention following from the initial diagnosis by Vscan, two and one respectively are under follow-up in the valve clinic, while two and four respectively refused TTE or follow-up. Two patients with moderate MR by Vscan had mild and mild/moderate MR respectively by TTE and were discharged. Total cost for scanning 100 patients was $18,201 - i.e. $182/patient. CONCLUSIONS: Screening with a hand-held scanner (Vscan), we identified 5/100 elderly subjects who needed valve replacement or follow-up in valve clinic, at a cost of $182/patient. These findings have potential significance for the allocation of resources in the context of an ageing population.

ST elevation in a patient with small bowel occlusion and gastric distension-What is the most likely explanation? A hypothesis generating case report.

We report a case of ST segment elevation and PR depression in inferolateral leads in a patient with small bowel occlusion and gastric distension that disappeared immediately after gastric evacuation. Contrary to prior reports, we believe that these ECG changes do not represent an intrinsic cardiac electrical abnormality, but are likely artefactual. We hypothesise that the accumulated air between the heart, lower limbs and left precordial electrodes result in a significant departure from the simplified assumptions of standard 12 lead ECG analysis (that the electrical activity of the heart can be described by an electrical dipole at a fixed location in an electrical homogeneous sphere) in such a way that the ECG filtering process will not compensate for this bias and will artificially create the ECG pattern described in this report.

Hand-held ultrasonography: An opportunity for "hands-on" teaching of medicine.

This article was migrated. The article was marked as recommended. Background: As ultrasound offers students an opportunity to study anatomy, physiology and pathophysiology actively, we used hand-held ultrasound (HHU) devices to augment current teaching of cardiac murmurs and pathology. Methods: Three types of teaching sessions (of different duration) were explored: 1) compulsory teaching on cardiac murmurs (n=40); 2) extra-curricular teaching of cardiac murmurs (n=8); 3) extra-curricular ultrasound course (n=6). We assessed students' ability to identify valvular lesions on auscultation, and anatomy and pathology on echocardiography, and sought qualitative feedback. Results: Using echocardiography to teach murmurs improved murmur recognition by auscultation alone from 23% pre-test to 93% post-test (p=0.017). Students were able to identify major cardiac anatomical landmarks on echo images (57% vs 98% ( p=0.027) in the voluntary teaching session lasting 90 minutes, and 40% vs 82% ( p=0.027) after the 3 week cardiac ultrasound course. The mean accuracy for diagnosing cardiac pathology on a printed image alone after the 3 week ultrasound course was 71%. Students unanimously found the sessions useful and engaging, and reported they would like further teaching about using ultrasound. Conclusion: Medical students found the sessions engaging, enjoyed this novel way of teaching and would like further teaching using ultrasound. Using hand-held ultrasound scanners to augment the teaching of cardiac murmurs to medical students is feasible and effective.

Do left atrial strain and strain rate reflect intrinsic atrial function, or are they determined by left ventricular function?

BACKGROUND: Left atrial (LA) strain (S) and strain rate (SR) are reported as measures of intrinsic function. AIM: Since the LA and left ventricle (LV) are connected through the mitral annulus, we investigated: (1) if deformation indices in the LA are mostly predicted by deformation of the LV; (2) if timings of S and SR events are similar in both the LA and LV; and (3) if alteration of S and SR in patients with primarily LV dysfunction would be similar in the LA and LV. METHODS: We retrospectively assessed 50 asymptomatic women (Group 1) and 20 patients with recent (< 96 h) acute pulmonary oedema (10 women) (Group 2). Using speckle tracking, the amplitude and timings of S and SR were averaged from three apical views, for one cardiac cycle, starting from the P-wave. RESULTS: In Group 1, all deformation indices were higher in the LA compared with the LV (p < 0.001 for all). In Group 2, S and SR during LA contraction were higher in the LA vs. LV (p < 0.05 for both), but all other deformation indices were not different in the LA vs. LV. All timings of S and SR occurred simultaneously in LA and LV in both groups, except S during LA contraction in Group 1, which occurred slightly earlier in LA than in LV. By multiple regression analysis, the most important predictors of LA deformation indices were the corresponding LV deformation indices, especially in patients with LV dysfunction (Group 1: r = 0.35-0.52; Group 2: r = 0.76-0.85; p < 0.05 by Fisher r-to-z transform). CONCLUSIONS: LA deformation strongly reflects LV deformation both in asymptomatic subjects and in patients with LV dysfunction. With the possible exception of LA contraction in asymptomatic individuals, discriminating intrinsic LA function from LV influence is difficult using deformation analysis.

Attenuated Salmonella enterica serovar Typhi expressing urease effectively immunizes mice against Helicobacter pylori challenge as part of a heterologous mucosal priming-parenteral boosting vaccination regimen.

Recombinant vaccine strains of Salmonella enterica serovar Typhi capable of expressing Helicobacter pylori urease were generated by transforming strains CVD908 and CVD908-htrA with a plasmid harboring the ureAB genes under the control of an in vivo-inducible promoter. The plasmid did not interfere with the ability of either strain to replicate and persist in human monocytic cells or with their transient colonization of mouse lungs. When administered to mice intranasally, both recombinant strains elicited antiurease immune responses skewed towards a Th1 phenotype. Vaccinated mice exhibited strong immunoglobulin G2a (IgG2a)-biased antiurease antibody responses as well as splenocyte populations capable of proliferation and gamma interferon (IFNgamma) secretion in response to urease stimulation. Boosting of mice with subcutaneous injection of urease plus alum enhanced immune responses and led them to a more balanced Th1/Th2 phenotype. Following parenteral boost, IgG1 and IgG2a antiurease antibody titers were raised significantly, and strong urease-specific splenocyte proliferative responses, accompanied by IFNgamma as well as interleukin-4 (IL-4), IL-5, and IL-10 secretion, were detected. Neither immunization with urease-expressing S. enterica serovar Typhi alone nor immunization with urease plus alum alone conferred protection against challenge with a mouse-adapted strain of H. pylori; however, a vaccination protocol combining both immunization regimens was protective. This is the first report of effective vaccination against H. pylori with a combined mucosal prime-parenteral boost regimen in which serovar Typhi vaccine strains are used as antigen carriers. The significance of these findings with regard to development of a human vaccine against H. pylori and modulation of immune responses by heterologous prime-boost immunization regimens is discussed.