Addressing Diagnosis, Management, and Complication Challenges in Placenta Accreta Spectrum Disorder: A Descriptive Study.

INTRODUCTION: In light of increased cesarean section rates, the incidence of placenta accreta spectrum (PAS) disorder is increasing. Despite the establishment of clinical practice guidelines offering recommendations for early and effective PAS diagnosis and treatment, antepartum diagnosis of PAS remains a challenge. This ultimately risks poor mental health and poor physical maternal and neonatal health outcomes. CASE DESCRIPTIONS: This case series details the experience of two high-risk patients who remained undiagnosed for PAS until they presented with antenatal hemorrhage, leading ultimately to necessary, complex surgical interventions, which can only be optimally provide in a tertiary care center. Patient 1 is a 37-year-old woman with a history of three cesarean sections, which elevates her risk for PAS. She had placenta previa detected at 19 weeks, and placenta percreta diagnosed upon hemorrhage. During a hysterectomy, invasive placenta was found in the patient's bladder, leading to a cystotomy and right ureteric reimplantation. After discharge, she was diagnosed with a vesicovaginal fistula, and is currently awaiting surgical repair. Patient 2 is a 34-year-old woman with two previous cesarean sections. The patient had complete placenta previa detected at 19- and 32-week gestation scans. She presented with antepartum hemorrhage at 35 weeks and 2 days. An ultrasound showed thin myometrium at the scar site with significant vascularity. A hysterectomy was performed due to placental attachment issues, with significant blood loss. Both patients were at high risk for PAS based on past medical history, risk factors, and pathognomonic imaging findings. DISCUSSION: We highlight the importance of the implementation of clinical guidelines at non-tertiary healthcare centers. We offer clinical-guideline-informed recommendations for radiologists and antenatal care providers to promote early PAS diagnosis and, ultimately, better patient and neonatal outcomes through increased access to adequate care.

Molecular Analysis of Biliary Tract Cancers with the Custom 3' RACE-Based NGS Panel.

The technique 3' rapid amplification of cDNA ends (3' RACE) allows for detection of translocations with unknown gene partners located at the 3' end of the chimeric transcript. We composed a 3' RACE-based RNA sequencing panel for the analysis of FGFR1-4 gene rearrangements, detection of activating mutations located within FGFR1-4, IDH1/2, ERBB2 (HER2), KRAS, NRAS, BRAF, and PIK3CA genes, and measurement of the expression of ERBB2, PD-L1, and FGFR1-4 transcripts. This NGS panel was utilized for the molecular profiling of 168 biliary tract carcinomas (BTCs), including 83 intrahepatic cholangiocarcinomas (iCCAs), 44 extrahepatic cholangiocarcinomas (eCCAs), and 41 gallbladder adenocarcinomas (GBAs). The NGS failure rate was 3/168 (1.8%). iCCAs, but not other categories of BTCs, were characterized by frequent FGFR2 alterations (17/82, 20.7%) and IDH1/2 mutations (23/82, 28%). Other potentially druggable events included ERBB2 amplifications or mutations (7/165, 4.2% of all successfully analyzed BTCs) and BRAF p.V600E mutations (3/165, 1.8%). In addition to NGS, we analyzed microsatellite instability (MSI) using the standard five markers and revealed this event in 3/158 (1.9%) BTCs. There were no instances of ALK, ROS1, RET, and NTRK1-3 gene rearrangements or MET exon 14 skipping mutations. Parallel analysis of 47 iCCA samples with the Illumina TruSight Tumor 170 kit confirmed good performance of our NGS panel. In conclusion, targeted RNA sequencing coupled with the 3' RACE technology is an efficient tool for the molecular diagnostics of BTCs.

The Tailored Opioid Reduction Strategy (TORS): A Quality Improvement Initiative to Reduce Opioid Prescription Following Hysterectomy.

OBJECTIVE: To evaluate a tailored opioid reduction strategy (TORS) in minimizing opioid prescriptions for patients undergoing hysterectomy. METHODS: This quality improvement initiative was developed by multiple stakeholders at an academic hospital in a Canadian urban centre. The intervention consisted of a three-pronged approach: (1) patient and provider education, (2) perioperative multimodal analgesia, and (3) a targeted opioid reduction strategy. All eligible patients were asked to fill pre- and postoperative questionnaires. Analysis of outcomes pre- and post-TORS implementation as well as intervention compliance was performed. RESULTS: From September 2020 to April 2021, 133 patients who underwent hysterectomy were included in the study, 69 in the pre-intervention group and 64 in the post-intervention group. Of 133 hysterectomies, 78 (58.6%) were performed laparoscopically, 16 (12%) open, 14 (10.5%) vaginally, and 25 (18.8%) robotically. The rate of discharge opioid prescriptions was significantly reduced in the post-intervention group compared with the pre-intervention group (37/64, 58% versus 62/69, 90%, respectively, P < 0.001), as well as the amount of opioid prescribed in oral morphine equivalents (OME) (mean 47 mg pre-intervention, 28 mg post-intervention, P < 0.001). There was no significant difference in patient satisfaction or postoperative pain scores between groups. Overall, compliance with 2 or more components of TORS intervention was seen in 64/64 (100%) cases. CONCLUSION: TORS implementation was successful in reducing the rate of discharge opioid prescriptions and the total amount of opiates prescribed in patients undergoing hysterectomy with no decrease in patient satisfaction or change in postoperative pain scores. We believe it can be applied more broadly across different surgical patient populations to prevent opioid abuse.

Hydrolysis of Hexacarbonyltechnetium(I) Cation: Formation and Structure of Technetium Carbonyl Hydride 99Tc3H(CO)14.

Reaction of [99Tc(CO)6]ClO4 with alkali in aqueous solutions yields yellow 99Tc3H(CO)14 as the major product. On the other hand, [99TcH(CO)5] becomes the major product when the reaction with alkali is combined with the extraction into hexane. The molecular structure of 99Tc3H(CO)14, determined by SCXRD, is composed of the 99Tc2(CO)9 fragment bound to the 99Tc(CO)5 fragment via the hydrogen bridge and weak metal-metal bond. This compound crystallizes in the monoclinic system, space group P21/n, a = 9.6954(2) Å, b = 15.0985(3) Å, c = 14.5090(3) Å, and ß = 104.925(2)°. 99Tc3H(CO)14 was additionally characterized by IR spectroscopy. The mechanism of hydrolysis of [99Tc(CO)6]ClO4 was suggested.

Conjugates of amino acids and peptides with 5-o-mycaminosyltylonolide and their interaction with the ribosomal exit tunnel.

During protein synthesis the nascent polypeptide chain (NC) extends through the ribosomal exit tunnel (NPET). Also, the large group of macrolide antibiotics binds in the nascent peptide exit tunnel. In some cases interaction of NC with NPET leads to the ribosome stalling, a significant event in regulation of translation. In other cases NC-ribosome interactions lead to pauses in translation that play an important role in cotranslational folding of polypeptides emerging from the ribosome. The precise mechanism of NC recognition in NPET as well as factors that determine NC conformation in the ribosomal tunnel are unknown. A number of derivatives of the macrolide antibiotic 5-O-mycaminosyltylonolide (OMT) containing N-acylated amino acid or peptide residues were synthesized in order to study potential sites of NC-NPET interactions. The target compounds were prepared by conjugation of protected amino acids and peptides with the C23 hydroxyl group of the macrolide. These OMT derivatives showed high although varying abilities to inhibit the firefly luciferase synthesis in vitro. Three glycil-containing derivatives appeared to be strong inhibitors of translation, more potent than parental OMT. Molecular dynamics (MD) simulation of complexes of tylosin, OMT, and some of OMT derivatives with the large ribosomal subunit of E. coli illuminated a plausible reason for the high inhibitory activity of Boc-Gly-OMT. In addition, the MD study detected a new putative site of interaction of the nascent polypeptide chain with the NPET walls.

Interplay between the ribosomal tunnel, nascent chain, and macrolides influences drug inhibition.

Accumulating evidence suggests that, during translation, nascent chains can form specific interactions with ribosomal exit tunnel to regulate translation and promote initial folding events. The clinically important macrolide antibiotics bind within the exit tunnel and inhibit translation by preventing progression of the nascent chain and inducing peptidyl-tRNA drop-off. Here, we have synthesized amino acid- and peptide-containing macrolides, which are used to demonstrate that distinct amino acids and peptides can establish interaction with components of the ribosomal tunnel and enhance the ribosome-binding and inhibitory properties of the macrolide drugs, consistent with the concept that the exit tunnel is not simply a Teflon-like channel. Surprisingly, we find that macrolide antibiotics do not inhibit translation of all nascent chains similarly, but rather exhibit polypeptide-specific inhibitory effects, providing a change to our general mechanistic understanding of macrolide inhibition.

Effect of tocopherol-monoglucoside (TMG), a water-soluble glycosylated derivate of vitamin E, on hematopoietic recovery in irradiated mice.

A preparation of alpha-tocopherol monoglucoside (TMG) administered i.p. at a dose of 600 mg/kg immediately after whole body gamma irradiation was examined for its radioprotective efficacy towards bone marrow and peripheral blood nucleated cells. When mice received X-rays at a dose of 5,6 Gy, a marked decrease in bone marrow karyocytes and a reduction of peripheral leukocytes within the early post-irradiated period were observed. However these changes were attenuated in TMG-treated mice. Significant protection of blood lymphocytes was found for the TMG group of mice. The return to normal value of the reduced blood leukocyte count starting from the 8th day was more rapid in TMG-treated mice than in untreated irradiated mice. TMG administration was found to enhance hematopoietic recovery, as measured by the exceeded nucleated bone marrow cell count due to elevated amount of both lymphoid and granulocytic elements in the TMG-group, in comparison with that of both control irradiated and non-irradiated animals. These findings indicate that the radioprotective effect of TMG is apparently realized through its influence on hematopoietic system.