Single-center outcome analysis of 46 fetuses with megacystis after intrauterine vesico-amniotic shunting with the Somatex®intrauterine shunt.

OBJECTIVES: To assess the spectrum of underlying pathologies, the intrauterine course and postnatal outcome of 46 fetuses with megacystis that underwent intrauterine vesico-amniotic shunting (VAS) with the Somatex® shunt in a single center. METHODS: Retrospective analysis of 46 fetuses with megacystis that underwent VAS either up to 14 + 0 weeks (early VAS), between 14 + 1 and 17 + 0 weeks (intermediate VAS) or after 17 + 0 weeks of gestation (late VAS) in a single tertiary referral center. Intrauterine course, underlying pathology and postnatal outcome were assessed and correlated with the underlying pathology and gestational age at first VAS. RESULTS: 46 fetuses underwent VAS, 41 (89%) were male and 5 (11%) were female. 28 (61%) fetuses had isolated and 18 (39%) had complex megacystis with either aneuploidy (n = 1), anorectal malformations (n = 6), cloacal malformations (n = 3), congenital anomalies overlapping with VACTER association (n = 6) or Megacystis-Microcolon Intestinal-Hypoperistalsis Syndrome (MMIHS) (n = 2). The sonographic 'keyhole sign' significantly predicted isolated megacystis (p < 0.001). 7 pregnancies were terminated, 4 babies died in the neonatal period, 1 baby died at the age of 2.5 months and 34 (74%) infants survived until last follow-up. After exclusion of the terminated pregnancies, intention-to-treat survival rate was 87%. Mean follow-up period was 24 months (range 1-72). The underlying pathology was highly variable and included posterior urethral valve (46%), hypoplastic or atretic urethra (35%), MMIHS or prune belly syndrome (10%) and primary vesico-ureteral reflux (2%). In 7% no pathology could be detected postnatally. No sonographic marker was identified to predict the underlying pathology prenatally. 14 fetuses underwent early, 24 intermediate and 8 late VAS. In the early VAS subgroup, amnion infusion prior to VAS was significantly less often necessary (7%), shunt complications were significantly less common (29%) and immediate kidney replacement therapy postnatally became less often necessary (0%). In contrast, preterm delivery ≤ 32 + 0 weeks was more common (30%) and survival rate was lower (70%) after early VAS compared to intermediate or late VAS. Overall, 90% of liveborn babies had sufficient kidney function without need for kidney replacement therapy until last follow-up, and 95% had sufficient pulmonary function without need for mechanical respiratory support. 18% of babies with complex megacystis suffered from additional health restrictions due to their major concomitant malformations. CONCLUSIONS: Our data suggest that VAS is feasible from the first trimester onward. Early intervention has the potential to preserve neonatal kidney function in the majority of cases and enables neonatal survival in up to 87% of cases. Despite successful fetal intervention, parents should be aware of the potential of mid- or long-term kidney failure and of additional health impairments due to concomitant extra-renal anomalies that cannot be excluded at time of intervention.

D-Transposition of the great arteries with restrictive foramen ovale in the fetus: the dilemma of predicting the need for postnatal urgent balloon atrial septostomy.

OBJECTIVE: Restrictive foramen ovale (FO) in dextro-transposition of the great arteries (d-TGA) with intact ventricular septum may lead to severe life-threatening hypoxia within the first hours of life, making urgent balloon atrial septostomy (BAS) inevitable. Reliable prenatal prediction of restrictive FO is crucial in these cases. However, current prenatal echocardiographic markers show low predictive value, and prenatal prediction often fails with fatal consequences for a subset of newborns. In this study, we described our experience and aimed to identify reliable predictive markers for BAS. METHODS: We included 45 fetuses with isolated d-TGA that were diagnosed and delivered between 2010 and 2022 in two large German tertiary referral centers. Inclusion criteria were the availability of former prenatal ultrasound reports, of stored echocardiographic videos and still images, which had to be obtained within the last 14 days prior to delivery and that were of sufficient quality for retrospective re-analysis. Cardiac parameters were retrospectively assessed and their predictive value was evaluated. RESULTS: Among the 45 included fetuses with d-TGA, 22 neonates had restrictive FO postnatally and required urgent BAS within the first 24 h of life. In contrast, 23 neonates had normal FO anatomy, but 4 of them unexpectedly showed inadequate interatrial mixing despite their normal FO anatomy, rapidly developed hypoxia and also required urgent BAS ('bad mixer'). Overall, 26 (58%) neonates required urgent BAS, whereas 19 (42%) achieved good O2 saturation and did not undergo urgent BAS. In the former prenatal ultrasound reports, restrictive FO with subsequent urgent BAS was correctly predicted in 11 of 22 cases (50% sensitivity), whereas a normal FO anatomy was correctly predicted in 19 of 23 cases (83% specificity). After current re-analysis of the stored videos and images, we identified three highly significant markers for restrictive FO: a FO diameter < 7 mm (p < 0.01), a fixed (p = 0.035) and a hypermobile (p = 0.014) FO flap. The maximum systolic flow velocities in the pulmonary veins were also significantly increased in restrictive FO (p = 0.021), but no cut-off value to reliably predict restrictive FO could be identified. If the above markers are applied, all 22 cases with restrictive FO and all 23 cases with normal FO anatomy could correctly be predicted (100% positive predictive value). Correct prediction of urgent BAS also succeeded in all 22 cases with restrictive FO (100% PPV), but naturally failed in 4 of the 23 cases with correctly predicted normal FO ('bad mixer') (82.6% negative predictive value). CONCLUSION: Precise assessment of FO size and FO flap motility allows a reliable prenatal prediction of both restrictive and normal FO anatomy postnatally. Prediction of likelihood of urgent BAS also succeeds reliably in all fetuses with restrictive FO, but identification of the small subset of fetuses that also requires urgent BAS despite their normal FO anatomy fails, because the ability of sufficient postnatal interatrial mixing cannot be predicted prenatally. Therefore, all fetuses with prenatally diagnosed d-TGA should always be delivered in a tertiary center with cardiac catheter stand-by, allowing BAS within the first 24 h after birth, regardless of their predicted FO anatomy.

The 48-hour tetrahydrobiopterin loading test in patients with phenylketonuria: evaluation of protocol and influence of baseline phenylalanine concentration.

BACKGROUND: The 24- and 48-hour tetrahydrobiopterin (BH4) loading test (BLT) performed at a minimum baseline phenylalanine concentration of 400 µmol/l is commonly used to test phenylketonuria patients for BH4 responsiveness. This study aimed to analyze differences between the 24- and 48-hour BLT and the necessity of the 400 µmol/l minimum baseline phenylalanine concentration. METHODS: Data on 186 phenylketonuria patients were collected. Patients were supplemented with phenylalanine if phenylalanine was <400 µmol/l. BH4 20mg/kg was administered at T = 0 and T = 24. Blood samples were taken at T=0, 8, 16, 24 and 48 h. Responsiveness was defined as ≥ 30% reduction in phenylalanine concentration at ≥ 1 time point. RESULTS: Eighty-six (46.2%) patients were responsive. Among responders 84% showed a ≥ 30% response at T = 48. Fifty-three percent had their maximal decrease at T = 48. Fourteen patients had ≥ 30% phenylalanine decrease not before T = 48. A ≥ 30% decrease was also seen in patients with phenylalanine concentrations <400 µmol/l. CONCLUSION: In the 48-hour BLT, T = 48 seems more informative than T = 24. Sampling at T = 32, and T = 40 may have additional value. BH4 responsiveness can also be predicted with baseline blood phenylalanine <400 µmol/l, when the BLT is positive. Therefore, if these results are confirmed by data on long-term BH4 responsiveness, we advise to first perform a BLT without phenylalanine loading and re-test at higher phenylalanine concentrations when no response is seen. Most likely, the 48-hour BLT is a good indicator for BH4 responsiveness, but comparison with long term responsiveness is necessary.

The success of dietary protein restriction in alkaptonuria patients is age-dependent.

Alkaptonuria is characterized by an increased urinary excretion of homogentisic acid, pigmentation of cartilage and connective tissues, and ultimately the development of inflammatory arthropathy. Various diets low in protein have been designed to decrease homogentisic acid excretion and to prevent the ochronotic pigmentation and arthritic lesions. However, limited information is available on the long-term beneficial effects of these diets. We reviewed the medical records of 16 patients aged 3-27 years (4 > 18 years) to ascertain the age of diagnosis, growth, development, social behaviour, signs of complications and longitudinal dietary compliance. The diagnosis of alkaptonuria was made at an average age of 1.4 years (2 months-4 years); following the diagnosis all patients were prescribed a diet with a protein content of 1.5 g/kg per day. All patients showed normal growth and development, and no major complications of the disease. Behavioural problems associated with poor dietary compliance emerged as the main problem. Dietary compliance decreased progressively with age. The effect of dietary protein restriction in homogentisic acid excretion was studied by fixing the amounts of protein in the diet at 1 g/kg per day and 3.5-5 g/kg per day during 8 days. Twelve patients, aged 4-27 years, participated in the investigation. Protein restriction resulted in a significantly lower excretion of homogentisic acid in the urine of children younger than 12 years (p < 0.01), whereas this effect was less obvious for adolescent and adult patients. The results suggest that restriction of protein intake may have a beneficial effect on alkaptonuric children; but continuation of this regimen to older age seems questionable and not practical.

Factors associated with postoperative pulmonary complications in patients with severe chronic obstructive pulmonary disease.

The purpose of this study was to determine the incidence of different postoperative pulmonary complications (PPCs) and their associated risk factors in patients with severe chronic obstructive pulmonary disease (COPD) (forced expiratory volume in 1 s [FEV1] < or = 1.2 L and FEV1/forced vital capacity (FVC) < 75%) undergoing noncardiothoracic operations. Thirty-nine of 105 patients (37%) had one or more PPCs (death, pneumonia, prolonged intubation, refractory bronchospasm, or prolonged intensive care unit (ICU) stay). Thirty-eight of 39 patients (97%) with a PPC had an anesthetic duration > 2 h. Our study patients had a 47% 2-yr mortality rate. We determined specific risk factors for each PPC by analyzing potential preoperative and intraoperative risk factors. Pulmonary factors alone do not predict the likelihood of PPCs in severe COPD patients. Multiple logistic regression identified composite scoring systems, such as the ASA physical status, as the best preoperative predictors of PPCs, probably because they include both pulmonary and nonpulmonary factors. During the intraoperative period, avoiding general anesthesia with tracheal intubation may decrease the risk of postoperative bronchospasm. Shortening the duration of surgery and anesthesia may decrease the risk of prolonged ICU stay.

A new method of two-resuscitator CPR.

Standard two-resuscitator cardiopulmonary resuscitation (CPR) (one resuscitator providing Bag Valve Mask (BVM) ventilation and one chest compressions) was compared with a modified method where one resuscitator held the mask while the second provided ventilation and compressions. Twenty-two subjects used both methods in random order on a recording manikin equipped to measure minute volume (Vm), tidal volume (Vt), respiratory rate (RR), compression rate (CR) and depth. Vm and Vt were greater with modified CPR, but the CR was slower. Percent of compressions < 38 mm, 38-51 mm or > 51 mm did not differ between techniques ((Modified--VM, 12.6 1 (S.D. 2.5); Vt, 1110 ml (S.D. 116); CR, 57 (S.D. 11), < 38 mm 6% (S.D. 14), 38-51 mm 36% (S.D. 33), > 51 mm 58% (S.D. 41); Standard--Vm, 9.7 1 (S.D. 3.8); Vt, 640 ml (S.D. 230); CR, 75 (10), < 38 mm 9% (S.D. 22), 38-51 mm 52% (S.D. 37), > 51 mm 38% (S.D. 38)). Modified CPR greatly improves ventilation but reduces CR.

Changes in renal vein, renal surface, and urine oxygen tension during hypoxia in pigs.

To determine whether ureteral urine oxygen tension could serve as a monitor of renal hypoxia and its relationship to other renal O2 tension parameters, we simultaneously measured femoral artery (PaO2), renal vein (PrvO2), renal surface (PrsO2), and ureteral urine (PuO2) oxygen tensions in 8 anesthetized pigs while incrementally decreasing the inspired oxygen concentration (FiO2) from 21% to 12%. Renal artery blood flow, measured by transit time ultrasound, renal oxygen consumption, and thermodilution cardiac output, was constant. Changes in PaO2, PrvO2, PrsO2, and PuO2 caused by decreasing FiO2 were evaluated by one-way analysis of variance. The relationships between PuO2 and the other O2 tension parameters were evaluated by correlation coefficient and linear regression statistics. Of six possible O2 decrements (combinations of 3, 6, and 9%), only PrvO2 significantly decreased with all six decrements. PuO2 decreased when FiO2 decreased 6% or more. PuO2 is not a sensitive indicator of systemic hypoxia. Under constant renal perfusion and oxygen consumption, PuO2 had a correlation coefficient of 0.80 and a regression equation of PuO2 = 0.84 (PrvO2) + 11.6, with PrvO2. PuO2 is related to PrvO2 when renal perfusion is constant.