Vascular Ehlers‐Danlos syndrome: A null COL3A1 variant found in a patient with loin pain without marked cutaneous features (case report)

Key Clinical Message Patients with null variants may have milder vascular Ehlers‐Danlos syndrome, presenting with seemingly non‐specific complaints and subtle cutaneous features that may be missed. A high index of suspicion and early genetic testing (aided by next‐generation sequencing) were crucial for prevention of life‐threatening complications in the patient and family members

GCK‐MODY in pregnancy: A pregnant woman with diabetes and a small‐for‐gestational‐age fetus

Abstract Glucokinase‐maturity‐onset diabetes of the young (GCK‐MODY) is often misdiagnosed as other forms of diabetes. A 42‐year‐old pregnant lady with pre‐existing diabetes was treated with insulin during first trimester. Fetal growth restriction was noted since mid‐second trimester. Genetic testing suggested the diagnosis of GCK‐MODY

Circulating Bacterial-Derived DNA Fragment Level Is a Strong Predictor of Cardiovascular Disease in Peritoneal Dialysis Patients

<div><p>Background</p><p>Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that plasma bacterial DNA level predicts cardiovascular events in new PD patients.</p><p>Methods</p><p>We measured plasma bacterial DNA level in 191 new PD patients, who were then followed for at least a year for the development of cardiovascular event, hospitalization, and patient survival.</p><p>Results</p><p>The average age was 59.3 ± 11.8 years; plasma bacterial DNA level 34.9 ± 1.5 cycles; average follow up 23.2 ± 9.7 months. At 24 months, the event-free survival was 86.1%, 69.8%, 55.4% and 30.8% for plasma bacterial DNA level quartiles I, II, III and IV, respectively (p < 0.0001). After adjusting for confounders, plasma bacterial DNA level, baseline residual renal function and malnutrition-inflammation score were independent predictors of composite cardiovascular end-point; each doubling in plasma bacterial DNA level confers a 26.9% (95% confidence interval, 13.0 – 42.5%) excess in risk. Plasma bacterial DNA also correlated with the number of hospital admission (r = -0.379, p < 0.0001) and duration of hospitalization for cardiovascular reasons (r = -0.386, p < 0.0001). Plasma bacterial DNA level did not correlate with baseline arterial pulse wave velocity (PWV), but with the change in carotid-radial PWV in one year (r = -0.238, p = 0.005).</p><p>Conclusions</p><p>Circulating bacterial DNA fragment level is a strong predictor of cardiovascular event, need of hospitalization, as well as the progressive change in arterial stiffness in new PD patients.</p></div

Kaplan-Meier plot of (A) event-free survival; and (B) cardiovascular disease-free survival (excluding congestive heart failure).

<p>Patients were divided to quartiles of plasma bacterial DNA. Quartile I had the lowest while quartile IV the highest plasma bacterial DNA level. Data are compared by the log rank test.</p

Baseline demographic and clinical data.

<p>PD, peritoneal dialysis; PCR, polymerase chain reaction. Patients were divided to quartiles of plasma bacterial DNA. Quartile I had the lowest while quartile IV the highest plasma bacterial DNA level. Note that a higher PCR cycle number indicates a lower level of bacterial DNA. Data are compared by Chi square test or one way analysis of variance (ANOVA) as appropriate.</p><p>Baseline demographic and clinical data.</p

Baseline biochemical data and dialysis prescription.

<p>HDL, high density lipoprotein; LDL, low density lipoprotein; D/P, dialysate-to-plasma concentration ratio of creatinine; MTAC, mass transfer area coefficient; GFR, glomerular filtration rate; NPNA, normalized protein nitrogen appearance; FEBM, fat-free edema-free body mass by creatinine kinetics. Patients were divided to quartiles of plasma bacterial DNA. Quartile I had the lowest while quartile IV the highest plasma bacterial DNA level. Data are compared by one way analysis of variance (ANOVA).</p><p>Baseline biochemical data and dialysis prescription.</p

Comparison of (A) carotid-radial; and (B) carotid-femoral pulse wave velocity (PWV) between quartiles of plasma bacterial DNA level.

<p>Quartile I had the lowest while quartile IV the highest plasma bacterial DNA level. P values depicted are computed by paired Student’s t test.</p

Independent predictors of hospitalization for cardiovascular reasons by log-linear model.

<p>CI, confidence interval; MIS, malnutrition inflammation score.</p><p>NB. e^COEF was the exponential coefficient indicating the relative number of hospital admission (per year) or duration of hospitalization (days per year of follow up) compared to the 2-fold lower of plasma bacterial DNA level (i.e. one extra threshold cycle of polymerase chain reaction), and 1 point less for MIS.</p><p>Independent predictors of hospitalization for cardiovascular reasons by log-linear model.</p

Comparison of (A) number of hospital admission; and (B) duration of hospitalization between quartiles of plasma bacterial DNA level.

<p>Quartile I had the lowest while quartile IV the highest plasma bacterial DNA level. (p < 0.0001 by Kruskal Wallis test for all comparisons between quartiles) (White box, hospitalization for all cause; hatched box, hospitalization for cardiovascular reasons.)</p