The Albert Schweitzer Fellowship

With new and increasingly sensitive techniques for genetic testing, genes that are newly related to a phenotype or disease are still identified, warranting for adequate phenotyping. Recently, 11 variants in the ZFX gene were reported to cause a distinct X-linked neurodevelopmental disorder in 18 male patients, and a female was reported with hyperparathyroidism in concurrence with a ZFX variant. In this report, we present a male patient and his mother with a new likely pathogenic variant in the ZFX gene (NM_003410.4(ZFX): c.2363C > G, p. Pro788Arg). The phenotype of the patient includes a global neurodevelopmental delay and several additional features greatly overlapping with the phenotype in previously described patients, including facial features, hypotonia, diminished white matter and thin corpus callosum, inguinal and umbilical herniation, and ophthalmological abnormalities. An elevated PTH was noted, with normocalcemia, a possible early sign of hyperparathyroidism. Additionally, a small colon, signs of a bleeding diathesis and a cervical swelling of non-specific origin were present, which were not reported in patients with ZFX variants before. The mother presents with fatigue, low iron status and a slight elevation of PTH with normocalcemia. This report adds valuable data to the phenotypical spectrum of the ZFX-related neurodevelopmental disorder.

Surgical site infections (SSI) are common. We selected five interventions from recent SSI prevention guidelines, to form the Enhanced PeriOperative Care and Health program (EPO₂CH), a perioperative care bundle. We aimed to investigate the effect of the EPO₂CH bundle on the incidence of SSI.

The EPO₂CH trial concerns an open label, pragmatic, randomised controlled parallel-group multicentre trial, in which we assigned patients, scheduled for elective abdominal surgery with incisions larger than five centimetres, to either standard care or standard care plus the EPO₂CH bundle consisting of intraoperative high fraction of inspired oxygen; Goal-Directed Fluid Therapy; normothermia; perioperative glucose control; and incisional wound irrigation. The study was conducted in seven hospitals in the Netherlands. Patients were randomised per hospital per day in a 1:1 ratio with variable block sizes using an internet-based automated assignment system. The primary outcome was the incidence of SSI within 30 days in the intention-to-treat population. This study is registered at CCMO register (NL-OMON50566).

Between March 1st, 2016, and March 26th, 2020, 1777 patients were included. The intervention group included 869 patients (mean age 63.1, 467 female and 402 male) versus 908 in the control group (mean age 64.0, 530 female and 378 male). The incidence of SSI was 18.4% (160/869) in the intervention and 18.9% (172/908) in the control group; relative risk 0.98 (95% CI: 0.81-1.18) in the intention-to-treat analysis and 0.91 (95% CI: 0.60-1.37) in the per-protocol analysis. The percentage of patients with a serious adverse event was 33.3% (289/869) versus 33.5% (304/908), RR 0.99, 95% CI 0.87-1.23.

In a high-income health care setting, a care bundle did not lead to a lower incidence of surgical site infections when added to standard care including preoperative systemic antibiotic prophylaxis and alcohol-based surgical skin preparation. Considering the persistent high risk of SSI, research into interventions that may help to reduce this risk remains urgently needed.

The Netherlands Organisation for Health Research and Development (ZonMW), and co-financed by Innovatiefonds Zorgverzekeraars, and Ethicon.

Sustained fetal tachycardia requires transplacental anti-arrhythmic therapy. Little is known about the dose-concentration-effect correlation and safety in the mother, fetus, and newborn.

This study evaluates the relationship between maternal dose of digoxin and flecainide therapy for fetal tachycardia, maternal and umbilical cord concentrations, and side effects.

This was a retrospective case series. We included 28 pregnant women initially treated with digoxin monotherapy for fetal tachycardia between June 2007 and January 2023. The main end point was the correlation between maternal drug exposure, effect, and side effects.

Oral digoxin monotherapy converted 9 fetuses (32%) to sinus rhythm after a median of 4.5 days (interquartile range [IQR] 3-6.5). Overall, 18 fetuses required additional oral flecainide (300 mg daily), resulting in a total conversion rate of 93% (26/28). Equal starting doses of digoxin caused similar maternal digoxin concentrations regardless of gestational age, with no significant difference between responders and non-responders (P = .504). Side effects, primarily nausea, led to dose reductions, but treatment remained effective. Maternal digoxin concentrations remained stable throughout pregnancy and little inter-patient variability was observed. Flecainide exposure varied both within and between patients. The median fetus/mother digoxin ratio was similar in both monotherapy (n = 3) and combination (n = 9) therapy groups (0.51 (IQR 0.28-0.76) vs 0.45 (IQR 0.39-0.64), P = .864). The median fetus/mother flecainide ratio was 0.82 (IQR 0.69-1.29).

Digoxin monotherapy successfully treated fetal tachycardia in only 32% of cases. Adding flecainide improved response to 93%, although it increased side effects, which could be managed with dose reductions. Maternal digoxin levels were stable throughout pregnancy.