Implication of chromosomal microarray analysis prior to in-utero repair of fetal open neural tube defect.

OBJECTIVE: In-utero repair of open neural tube defects (ONTD) is an accepted treatment option with demonstrated superior outcome for eligible patients. While current guidelines recommend genetic testing by chromosomal microarray analysis (CMA) when a major congenital anomaly is detected prenatally, the requirement for an in-utero repair, based on the Management of Myelomeningocele Study (MOMS) criteria, is a normal karyotype. In this study, we aimed to evaluate if CMA should be recommended as a prerequisite for in-utero ONTD repair. METHODS: This was a retrospective cohort study of pregnancies complicated by ONTD that underwent laparotomy-assisted fetoscopic repair or open-hysterotomy fetal surgery at a single tertiary center between September 2011 and July 2021. All patients met the MOMS eligibility criteria and had a normal karyotype. In a subset of the pregnancies (n = 77), CMA testing was also conducted. We reviewed the CMA results and divided the cohort into two groups according to whether clinically reportable copy-number variants (CNV) were detected (reportable-CNV group) or not (normal-CMA group). Surgical characteristics, complications, and maternal and early neonatal outcomes were compared between the two groups. The primary outcomes were fetal or neonatal death, hydrocephalus, motor function at 12 months of age and walking status at 30 months of age. Standard parametric and non-parametric statistical tests were employed as appropriate. RESULTS: During the study period, 146 fetuses with ONTD were eligible for and underwent in-utero repair. CMA results were available for 77 (52.7%) patients. Of those, 65 (84%) had a normal CMA and 12 (16%) had a reportable CNV, two of which were classified as pathogenic. The first case with a pathogenic CNV was diagnosed with a 749-kb central 22q11.21 deletion spanning low-copy-repeat regions B-D of chromosome 22; the second case was diagnosed with a 1.3-Mb interstitial deletion at 1q21.1q21.2. Maternal demographics, clinical characteristics, operative data and postoperative complications were similar between those with normal CMA results and those with reportable CNVs. There were no significant differences in gestational age at delivery or any obstetric and early neonatal outcome between the study groups. Motor function at birth and at 12 months of age, and walking status at 30 months of age, were similar between the two groups. CONCLUSIONS: Standard diagnostic testing with CMA should be offered when an ONTD is detected prenatally, as this approach has implications for counseling regarding prognosis and recurrence risk. Our results indicate that the presence of a clinically reportable CNV should not a priori affect eligibility for in-utero repair, as overall pregnancy outcome is similar in these cases to that of cases with normal CMA. Nevertheless, significant CMA results will require a case-by-case multidisciplinary discussion to evaluate eligibility. To generalize the conclusion of this single-center series, a larger, multicenter long-term study should be considered. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Cryogenic gas loading in a Mao-Bell-type diamond anvil cell for high pressure-high temperature investigations.

A simple system for loading argon fluid at cryogenic temperatures in a Mao-Bell-type diamond anvil cell (DAC) has been developed. It is done in a two step process in which the piston-cylinder assembly alone is submerged in the cryogenic chamber for trapping the liquefied inert gas. Liquid nitrogen is used for condensing the argon gas. This system is now being efficiently used for loading liquid argon in the DAC for high pressure-high temperature experiments. The success rate of trapping liquefied argon in the sample chamber is about 75%. The performance of the gas loading system is successfully tested by carrying out direct conversion of pyrolitic graphite to diamond under high pressure-high temperature using laser heated DAC facility.

Interposition arthroplasty for osteoarthritis of trapezio metacarpal joint: results of a modified incision and technique of interposing with early mobilisation.

Sixty flexor carpi radialis (FCR) tendon interposition arthroplasties were done using a modified incision from Froimson's approach for osteoarthritis (OA) of thumb carpo metacarpal joint (CMCJ) The tendon was made to resemble an anchovy fillet to preserve pillar length (average 7.5 mm). There was no incidence of injury to the superficial branch of the radial nerve. Graded mobilisation was commenced at two weeks. Our average follow-up for five and a half years shows good results, viz. pain relief (100%), power grip (21 kg), pinch grip (4.2 kg), tripod grip (5.5 kg), key grip (6.5 kg), ability to touch base and tip of little finger (91.6%) and (96.6%), respectively. Activities of daily living (ADL) without pain in turning a key (96.7%), opening jar top (100%), bottle top (93.4%), wringing cloth (86.7%), and using scissors (88.4%). None of them suffered reflex sympathetic dystrophy (RSD) and mobility was almost equal to the non-operated hand. Our experience with this modified incision and technique of interposing with early mobilisation has shown good functional outcome with no significant operative or postoperative complications.

"Dehydrogenase" and "oxidase" reactions of medium-chain fatty acyl-CoA dehydrogenase utilizing chromogenic substrates: role of the 3',5'-adenosine diphosphate moiety of the coenzyme A thioester in catalysis.

We undertook a comparative investigation of the medium-chain fatty acyl-CoA dehydrogenase (MCAD)-catalyzed reaction utilizing indole-, furyl-, and 4-(dimethylamino)phenyl-substituted propionyl- and acryloyl-CoAs as potential substrate/product pairs. All these propionyl-CoA derivatives undergo MCAD-catalyzed conversion into their corresponding acryloyl-CoAs via both "dehydrogenase" (in the presence of "organic" electron acceptors) and "oxidase" (buffer-dissolved oxygen serving as the electron acceptor) pathways [Johnson, J. K., Wang, Z. X., & Srivastava, D. K. (1992) Biochemistry 31, 10564-10575]. The steady-state kinetic parameters for the enzyme utilizing these substrates reveal that the KmS (for the CoA substrates) and kcatS for the dehydrogenase reaction are at least an order of magnitude higher than those for the oxidase reaction. As with the CoA substrates, the enzyme catalyzes the conversion of indolepropionyl pantetheine phosphate (IPPP) into indoleacryloyl pantetheine phosphate (IAPP) via these two pathways. However, with IPPP as substrate, the Km (for IPPP) and kcat values of the dehydrogenase and oxidase reactions are the same. These, coupled with the spectral changes of the enzyme-product complexes as well as the binding affinities of the enzyme-substrate/product complexes, lead to the following conclusions: (1) The aromatic/heterocyclic group-containing substrates are converted into their corresponding products via both the dehydrogenase and the oxidase pathways. (2) The 3',5'-ADP moiety of the CoA thioester provides a significant fraction of the total binding energy in stabilizing the enzyme-substrate/product complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Conservative medical management of traumatic pharyngoesophageal perforations.

Traditionally, surgical treatment has been the acceptable management for perforation of the pharyngoesophageal tract secondary to blunt and penetrating trauma. From July 1983 to June 1990, we managed 10 patients with this type of lesion by a conservative medical management approach. Mirror or fiberoptic flexible laryngoscopy was performed in the majority of cases to ascertain the nature of the injury. An esophagogram is very helpful to locate and evaluate the extent of the injury. All patients were treated with broad-spectrum intravenous antibiotic therapy and no oral feeding. There were no complications or need for surgical treatment in any of the cases. The head and neck surgeon, in selected cases, should consider the possibility of using conservative management of pharyngoesophageal perforations. This approach has proven in our hands to be relatively safe and cost-effective, resulting in no disability or prolonged hospitalization of our patients. This study involves two institutions (two affiliated hospitals of Case Western Reserve University School of Medicine) with different surgeons selecting appropriate antibiotic therapy. It is a retrospective review. No controls were made by random selection of cases treated surgically. These cases, if not properly managed, may lead to fatal outcomes.