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Objectives: Down syndrome (DS) is associated with airway abnormalities including a narrowed trachea. It is uncertain whether this narrowed trachea in DS is a consequence of deviant fetal development or an acquired disorder following endotracheal intubation after birth. This study aimed to compare the tracheal morphology in DS and non‐DS fetuses using microfocus computed tomography (micro‐CT). Methods: Twenty fetal samples were obtained from the Dutch Fetal Biobank and divided into groups based on gestational age. Micro‐CT images were processed to analyze tracheal length, volume, and cross‐sectional area (CSA). Results: Mean tracheal length and tracheal volume were similar in DS and non‐DS fetuses for all gestational age groups. Mean, minimum, and maximal tracheal CSA were statistically significantly increased in the single DS fetus in the group of 21–24 weeks of gestation, but not in other gestational age groups. In 90% of all studied fetuses, the minimum tracheal CSA was located in the middle third of the trachea. Conclusion: Tracheal development in DS fetuses was similar to non‐DS fetuses between 13 and 21 weeks of gestation. This suggests that the narrowed tracheal diameter in DS children may occur later in fetal development or results from postnatal intubation trauma. The narrowest part of the trachea is in majority of DS and non‐DS fetuses the middle third. Level of Evidence: 3 Laryngoscope, 134:4389–4395, 2024 [ABSTRACT FROM AUTHOR]

Introduction: The decision to terminate a pregnancy due to fetal anomalies can have a significant emotional impact, especially in second‐trimester terminations. Previous studies on the psychological consequences of pregnancy termination have had limitations, and little is known about the outcomes for partners and the impact of fetal donation. Therefore, we aimed to investigate the psychological effects of second‐trimester pregnancy termination and identify factors associated with outcomes in both women and men, including donation of fetal remains to science. Material and Methods: A longitudinal cohort study was conducted at the Amsterdam UMC in the Netherlands, involving women and partners who underwent termination at or before 23 weeks and 6 days of gestation. Questionnaires were administered at termination, 6 weeks, and 4 months after. We utilized validated questionnaires to assess psychological morbidity (grief, post‐traumatic stress and postnatal depression and quality of life [QoL]), and factors that could potentially influence outcomes. Results: Of 241 participants, women displayed more pronounced psychological distress than men, though both groups improved over time. Four months after termination, 27.4% of women and 9.1% of men showed signs of pathological grief. Scores indicative for postnatal depression occurred in 19.8% women and 4.1% of men. A prior psychiatric history was a consistent predictor of poorer outcomes. Fetal donation to the Dutch Fetal Biobank was associated with reduced likelihood of symptoms of complicated grief four months after termination. Conclusions: Second‐trimester termination of pregnancy for fetal anomalies can lead to psychological morbidity, particularly in women. However, there is a notable improvement over time for both groups. Individuals with prior psychiatric history appear more vulnerable post‐termination. Also, fetal donation to science did not have a negative impact on psychological well‐being. [ABSTRACT FROM AUTHOR]

Mitchell-Riley syndrome (MRS) is caused by recessive mutations in the regulatory factor X6 gene (RFX6) and is characterised by pancreatic hypoplasia and neonatal diabetes. To determine why individuals with MRS specifically lack pancreatic endocrine cells, we micro-CT imaged a 12-week-old foetus homozygous for the nonsense mutation RFX6 c.1129C>T, which revealed loss of the pancreas body and tail. From this foetus, we derived iPSCs and show that differentiation of these cells in vitro proceeds normally until generation of pancreatic endoderm, which is significantly reduced. We additionally generated an RFX6HA reporter allele by gene targeting in wild-type H9 cells to precisely define RFX6 expression and in parallel performed in situ hybridisation for RFX6 in the dorsal pancreatic bud of a Carnegie stage 14 human embryo. Both in vitro and in vivo, we find that RFX6 specifically labels a subset of PDX1-expressing pancreatic endoderm. In summary, RFX6 is essential for efficient differentiation of pancreatic endoderm, and its absence in individuals with MRS specifically impairs formation of endocrine cells of the pancreas head and tail. [ABSTRACT FROM AUTHOR]

Purpose: To study changes in flap thickness made with two different microkeratome heads across different corneal locations using anterior segment optical coherence tomography (OCT). Methods: In this prospective, non-randomized, consecutive case series, subjects who had their laser in-situ keratomileusis (LASIK) flaps made using 90 µm (MSU90) or 130 µm (MSU130) disposable M2 microkeratome heads were examined using OCT. The measurements were performed at three locations (central and 2.5 mm to either side) at 1 day, 1 week, and 1 month postoperatively. Results: The central flap thickness was 123 ± 15, 130 ± 14, and 127 ± 13 µm, respectively, at 1 day, 1 week, and 1 month postoperatively in the MSU90 group (41 eyes) and 142 ± 20, 147 ± 19, and 143 ± 15 µm, respectively, in the MSU130 group (47 eyes). At 1 month, peripheral flap thickness was 161 ± 17 and 159 ± 13 µm, respectively, at 2.5 mm to the right and left of corneal center in the MSU90 group. The corresponding figures were 170 ± 14 and 167 ± 13 µm, respectively, in the MSU130 group. There was a statistically significant difference between the two groups at all locations (P < 0.001). No statistically significant change in flap thickness was detected in either group at any assessment time. There was a partial positive correlation (after controlling for preoperative manifest refractive spherical equivalent) between central flap thickness and preoperative ultrasound central pachymetry (r = 0.739, P = 0.036) in the MSU90 group but not in the MSU130 group. Conclusion: Using OCT, changes in flap thickness were minimal in the first month after LASIK. Flap thickness correlated strongly with central corneal thickness if a 90 µm head was used. [ABSTRACT FROM AUTHOR]

Abstract: The isocitrate dehydrogenase 1 (IDH1) mutation occurs in high frequency in glioma and secondary glioblastoma (GBM). Mutated IDH1 produces the oncometabolite 2-hydroxyglutarate rather than α-ketoglutarate or isocitrate. The oncometabolite is considered to be the major cause of the association between the IDH1 mutation and gliomagenesis. On the other hand, the IDH1 mutation in GBM is associated with prolonged patient survival. This association is not well understood yet but IDH1 involvement in epigenetic silencing of O-6-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme is considered to be an important mechanism. However, it was shown recently that the IDH1 mutation and MGMT silencing are independent prognostic factors. Here, we hypothesize that the IDH1 mutation reduces the capacity to produce NADPH and thus reduces the capacity to scavenge reactive oxygen species that are generated during irradiation and chemotherapy. IDH1 activity is responsible for two-thirds of the NADPH production capacity in normal brain, whereas the IDH1 mutation reduces this capacity by almost 40%. Therefore, we hypothesize that the reduced NADPH production capacity due to the IDH1 mutation renders GBM cells more vulnerable to irradiation and chemotherapy thus prolonging survival of the patients. [Copyright &y& Elsevier]

Background Pterygium is a prevalent ocular surface aberrant growth that arises at the bulbar conjunctiva and attacks the cornea to varying degrees. This study was conducted to assess the efficacy and safety of the conjunctival autograft using fibrin glue and sutures in primary pterygium excision. Methods: Forty six eyes of 46 patients underwent surgical excision of primary pterygium. Autologous graft was taken from the superior bulbar conjunctiva to cover the sclera after the removal of pterygium. In 23 eyes, the transplants were kept attached to the sclera with fibrin glue, while in the other 23 eyes, the transplants were kept attached with 10/0 nylon sutures. Slit-lamp signs, patient symptoms, and patient cosmetic satisfaction were assessed and scaled. Patients were scheduled for follow-up for six months. Results: The operative time in the fibrin group (13.69±2.66 (8-20) min.) was significantly shorter than that of the suture group (22.25±4.9 (10-30) min) (P < 0.001). Pain, photophobia, stinging, watering, and discomfort were significantly lower in eyes in which the autograft had been attached with glue (P < 0.001). One case of recurrence for each group and one case of pyogenic granuloma in the suture group were noticed. Conclusions: The use of fibrin glue for attaching autografts after pterygium removal significantly reduces operative time and postoperative pain and discomfort. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the feasibility of postmortem ultra-high-field magnetic resonance imaging (UHF-MRI) to study fetal musculoskeletal anatomy and explore the contribution of variation in iodine and formaldehyde (paraformaldehyde, PFA) treatment of tissue., Methods: Seven upper extremities from human fetuses with gestational ages of 19 to 24 weeks were included in this experimental study, approved by the Medical Research Ethics Committee. The specimens were treated with various storage (0.2-4% PFA) and staining (Lugol's solution) protocols and the wrist joint was subsequently imaged with 7.0 T UHF-MRI. Soft-tissue contrast was quantified by determining regions of interest within a chondrified carpal bone (CCB) from the proximal row, the triangular fibrocartilage (TFC), and the pronator quadratus muscle (PQM) and calculating the contrast ratios (CRs) between mean signal intensities of CCB to TFC and CCB to PQM., Results: UHF-MRI showed excellent soft-tissue contrast in different musculoskeletal tissues. Increasing storage time in 4% PFA, CRs decreased, resulting in a shift from relatively hyperintense to hypointense identification of the CCB. Storage in 0.2% PFA barely influenced the CRs over time. Lugol's solution caused an increase in CRs and might have even contributed to the inversion of the CRs., Conclusions: UHF-MRI is a feasible technique to image musculoskeletal structures in fetal upper extremities and most successful after short storage in 4% PFA or prolonged storage in 0.2% PFA. The use of Lugol's solution is not detrimental on soft-tissue MRI contrast and therefore enables effectively combining UHF-MRI with contrast-enhanced micro-computed tomography using a single preparation of the specimen., Relevance Statement: UHF-MRI can be performed after CE-micro-CT to take advantage of both techniques., Key Points: • UHF-MRI is feasible to study human fetal cartilaginous and ligamentous anatomy. • Storage in low PFA concentrations (i.e., 0.2%) improves soft-tissue contrast in UHF-MRI. • Limited preservation time in high concentrations of PFA improves soft-tissue contrast in UHF-MRI. • Prior staining with Lugol's solution does not reduce soft-tissue contrast in UHF-MRI., (© 2023. The Author(s).)

Introduction:  Urothelial carcinoma of the urinary bladder is a tumour of advanced age. The demographic change increases the number of very old patients ( > 80 years) subjected to TUR-B., Material and Methods:  In a retrospective analysis, perioperative complications in 89 patients (> 80 years), who underwent a transurethral resection of the bladder between 2013 and 2016 in our department, were recorded and evaluated using the Clavien-Dindo grading system., Results:  Mean patient age was 87 years (82 - 94). 81 patients (91 %) were treated with oral anticoagulants (32 × ASA, 24 × NOACs, 25 × Marcumar). A histological examination revealed no tumour in 25/89 (28 %) patients, pTa in 28/89 (31 %), pT1 in 22/89 (25 %) and pT2 or higher in 14/89 patients (16 %), respectively. A total of 36/89 (40 %) patients experienced complications according to the Clavien-Dindo classification. 21/89 (23 %) of patients had a prolonged bladder irrigation due to macrohaematuria, 5/89 (6 %) needed surgical reintervention. 14 (12.4 %) patients needed a blood transfusion, 6 (5.3 %) of them preoperatively. According to the Clavien-Dindo classification, 4/89 (4 %) patients were graded as I, 21/89 (24 %) as II, 5/89 (6 %) as IIb and 3/89 (3 %) as IVa, respectively. Three patients (3 %) died postoperatively (Clavien-Dindo V). One of them died as a result of aspiration pneumonia (86 y, ASA IV), one as a result of pulmonary embolism (90 y, ASA IV) and one as a result of multiorgan failure (84 y, ASA III). In multivariate analyses, a tumour stage > T2 was confirmed as a significant predictor of the occurrence of postoperative complications (odds ratio of 9.541 (95 % CI 1.14 - 84.67 p = 0.032). For oral anticoagulants the odds ratio was 4.10 (95 % CI, 41.00 - 1.23, p = 0.050)., Conclusion: Overall, the data show that a TUR-B is feasible in patients > 80 years with an increased complication rate in comparison to younger patients. Prolonged macrohaematuria and a high transfusion rate are attributable to the high percentage of orally anticoagulated patients., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt vorliegt., (© Georg Thieme Verlag KG Stuttgart · New York.)