Complications, Adverse Drug Events, High Costs, and Disparities in Multisystem Inflammatory Syndrome in Children vs COVID-19.

Importance: Multisystem inflammatory syndrome in children (MIS-C) causes severe inflammation of multiple organ systems after SARS-CoV-2 infection. During the pandemic, surveillance reporting of MIS-C was voluntary, with likely underreporting. For a rare syndrome like MIS-C, numerous data are needed to explore the disease in greater detail. Objective: To use large all-payer billing data and the new International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification (ICD-10-CM) code for MIS-C to compare outcomes across MIS-C and COVID-19 over all 4057 hospitals in 31 states. Design, Setting, and Participants: A retrospective cross-sectional study of all COVID-19 and MIS-C hospitalizations in individuals younger than 21 years from 31 states was conducted, using Agency for Healthcare Research and Quality 2021 Healthcare Cost and Utilization Project data. Analyses were conducted from February 1 to October 20, 2022. Main Outcomes and Measures: Fifty complications, adverse medication events, costs, and the Social Vulnerability Index. Results: There were 4107 individuals with MIS-C (median age, 9 [IQR, 5-13] years; 2443 [59.5%] male; 1384 [38.1%] White) and 23 686 individuals with COVID-19 without MIS-C (median age, 15 [IQR, 5-18] years; 12 878 [54.4%] female; 4605 [44.1%] White), with 1.48 (95% CI, 1.35-1.62) MIS-C hospitalizations per 100 000 children per month, ranging from 0.97 hospitalizations per 100 children for White and 1.99 hospitalizations per 100 children for Black children. Outcomes worsened as the number of organ system dysfunctions increased from 2 to 8 organs. Deaths associated with MIS-C increased from less than 1% to 5.8% (95% CI, 3.3%-8.4%) and from less than 1% to 17.2% (95% CI, 11.7%-22.7%) for COVID-19 (P = .001). Adverse medication events associated with MIS-C increased from 4.9% (95% CI, 3.8%-6.0%) to 17.8% (95% CI, 13.7%-22.0%) and from 1.2% (95% CI, 1.0%-1.3%) to 13.4% (95% CI, 8.4%-18.3%) for COVID-19. The median length of stay for MIS-C increased from 4 (IQR, 2-5) to 8 (IQR, 5-12) days and from 3 (IQR, 2-5) to 16 (IQR, 7-23) days for COVID-19. Median costs for MIS-C increased from $16 225 (IQR, $9244-$26 822) to $53 359 (IQR, $35 920-$86 882) and from $6474 (IQR, $3741-$12 103) to $98 643 (IQR, $30 675-$204 956) for COVID-19. The percentage of MIS-C cases that were in Black children doubled from 16.2% to 31.7% (P = .001) as organ dysfunction increased, remaining unchanged with COVID-19. Hospital stays for MIS-C increased by 1 day (P = .01) for Black patients compared with White patients, with Black patients moving from the bottom to top quartile of socioeconomic vulnerability, with no disparity with COVID-19. Conclusions and Relevance: In this cross-sectional study, MIS-C was more common and severe than previously reported, with more racial disparities in outcomes than were seen in patients with COVID-19. The findings of this study suggest that relying on mean outcomes for MIS-C from past studies can be misleading, since outcomes and disparities varied widely with the number of multiorgan dysfunctions.

Critical stenosis of axillary artery treated with percutaneous angioplasty and stenting: a case report and review of the literature.

Focal axillary artery stenosis or occlusion is a rare occurrence that is most commonly encountered after severe trauma involving the shoulder joint or proximal humerus. Other etiologies that can lead to axillary artery injury or pathology include different vasculitides, radiation arteritis, crutch-injury, and peripheral arterial disease. In this case report, a 70-year-old woman was referred for asymmetrically decreased right brachial artery systolic pressure and right-hand paresthesia with overhead abduction. Further evaluation with imaging revealed critical stenosis of the right axillary artery. The focal stenotic lesion was treated with drug-coated balloon angioplasty and stent placement leading to in-line flow and resolution of symptoms. Duplex exam 6 months post-treatment demonstrated a widely patent right axillary artery stent without stenosis. Biannual clinic visits up to 2 years post stent placement confirmed resolution of symptoms.

Detection of Primary Malignancy and Metastases with FDG PET/CT in Patients with Cholangiocarcinomas: Lesion-based Comparison with Contrast Enhanced CT.

The current National Comprehensive Cancer Network (NCCN) Guidelines consider the role of 2-deoxy-2-(18)F-fluoro-d-glucose positron emission tomography/computer tomography (FDG PET/CT) in the evaluation of cholangiocarcinoma (CCA) as "uncertain," and have recommended contrast enhanced computed tomography (CECT) but not FDG PET/CT as a routine imaging test for CCA workup. We set out to compare the diagnostic performance of FDG PET/CT and CECT in patients with CCA. The retrospective study included patients with CCA who underwent FDG PET/CT and CECT within 2-month interval between 2011 and 2013 in our hospital. Lesion-based comparison was conducted. Final diagnoses were made based on the composite clinical and imaging data with minimal 6-month follow-up. A total of 18 patients with 28-paired tests were included. There is a total of 142 true malignant lesions as revealed by the 6-paired pre-treatment and 22-paired post-treatment tests. On a lesion-based analysis, the sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and accuracies of PET/CT and CECT for detection of CCA were 96.5%, 55.5%, 97.2%, 50.0%, 94.1% and 62.2%, 66.7%, 96.7%, 10.0%, 62.5%, respectively. FDG PET/CT detected more intrahepatic malignant and extrahepatic metastases; and had significant higher sensitivity, NPV, and accuracy than CECT, while similar in specificity and PPV. No true positive lesion detected on CECT that was missed on PET/CT, and none of the false negative lesions on PET/CT were detected on CECT. Six patients had paired pretreatment tests, and FDG PET/CT results changed planned management in three patients. Our data suggest that FDG PET/CT detect more primary and metastatic lesions and lead to considerable changes in treatment plan in comparison with CECT.

Tumor lysis syndrome and primary hepatic malignancy: case presentation and review of the literature.

Tumor lysis syndrome (TLS) represents a constellation of laboratory and clinical derangements that can occur following treatment of malignancies with high cellular turnover. Most commonly noted in hematologic malignancies, TLS has been reported to occur following liver-directed therapy in the form of both ablative therapies and transarterial therapies. Classification schemes exist, as do established diagnostic criteria, to aid in the definitive diagnosis of TLS. In addition, treatment algorithms are reported for patients with the diagnosis of TLS. This manuscript will review the risk factors associated with the development of TLS, the diagnostic criteria used, and treatment and preventative strategies employed. In addition, an algorithm for the diagnosis and treatment of TLS will be provided.

Tissue adhesive in free gingival graft / Adesivo tecidual no enxerto gengival livre

The aim of the present study was to review the literature regarding the utilization of 2-octyl cyanoacrylate's (Dermabond®, Ethicon US, USA) as a tissue adhesive in dentistry; also, to report its use in the stabilization and fixation of a free gingival graft, indicated to increase the width of the keratinized attached mucosa at the lower incisive region. Literature analysis revealed numerous indications for this tissue adhesive in the medical field related to maxillofacial injuries. In dentistry, clinical reports, as well as controlled clinical studies conducted in humans and in animal models, using histological analysis described positive results for the use of different cyanoacrylate-based tissue adhesives. These studies reported that the use of tissue adhesives reduced the surgical procedure time period, eliminated postoperative visits as well as the discomfort of suture removal and, in addition, did not interfere with the clinical repair process. Favorable results, like the ones described in the literature, were obtained in the present case report using Dermabond®.

O objetivo do presente estudo foi revisar a literatura pertinente sobre a utilização do 2-octil cianoacrilato (Dermabond®, Ethicon US, USA) como adesivo tecidual na Odontologia, assim como relatar seu uso na estabilização e fixação de um enxerto gengival livre indicado para aumento da mucosa ceratinizada inserida na região dos incisivos inferiores. A análise da literatura revelou ampla aplicabilidade deste adesivo tecidual na área médica relacionada aos ferimentos maxilofaciais. Na Odontologia existem relatos clínicos e estudos controlados em humanos e em modelos animais, descrevendo resultados positivos, inclusive por meio da análise histológica, sobre a utilização de diferentes adesivos teciduais, à base do cianocrilato. Estes estudos relataram que o uso dos adesivos teciduais, reduz o tempo operatório, elimina visitas pós-operatórias, não apresenta o desconforto da remoção de suturas, além de não interferir no processo de reparo clínico. Resultados favoráveis como os descritos na literatura, foram obtidos no presente relato de caso com a utilização do Dermabond®.

Adesivos teciduais a base de cianoacrilato / Tissular adhesives ofcyonoacrylote bases

O uso de adesivos teciduais à base de cianoacrilato como alternativa às suturas tem despertado grande interesse entre os cirurgiões, pela promoção de uma adesão de qualidade nos tecidos em tempo reduzido e, ainda, pelas suas propriedades hemostáticas e bacteriostáticas. Neste contexto, o presente estudo avaliou, através da revista da literatura, as propriedades dos diversos tipos de adesivos teciduais disponíveis e utilizados na Odontologia para a síntese de tecidos.

Experimental evidence for a link among cupredoxins: red, blue, and purple copper transformations in nitrous oxide reductase.

The cupredoxin fold is an important motif in numerous proteins that are central to several critical cellular processes ranging from aerobic and anaerobic respiration to catalysis and iron homeostasis. Three types of copper sites have been found to date within cupredoxin folds: blue type 1 (T1) copper, red type 2 (T2) copper, and purple Cu(A). Although as much as 90% sequence difference has been observed among some members of this superfamily of proteins that span several kingdoms, sequence alignment and phylogenic trees strongly suggest an evolutionary link and common ancestry. However, experimental evidence for such a link has been lacking. We report herein the observation of pH-dependent transformation between blue T1 copper, red T2 copper, and the native purple Cu(A) centers of nitrous oxide reductase (N2OR) from Paracoccus denitrificans. The blue and red copper centers form initially before they are transformed into purple Cu(A) center. This transformation process is pH-dependent, with lower pH resulting in fewer trapped T1 and T2 coppers and faster transition to purple Cu(A). These observations suggest that the purple Cu(A) site contains the essential elements of T1 and T2 copper centers and that the Cu(A) center is preferentially formed at low pH. Therefore, this work provides an underlying link between the various cupredoxin copper sites and possible experimental evidence in vitro for the evolutionary relationship between the cupredoxin proteins. The findings also lend physiological relevance to cupredoxin site biosynthesis.

Dissecting the roles of a strictly conserved tyrosine in substrate recognition and catalysis by pseudouridine 55 synthase.

Sequence alignment of the TruA, TruB, RsuA, and RluA families of pseudouridine synthases (PsiS) identifies a strictly conserved aspartic acid, which has been shown to be the critical nucleophile for the PsiS-catalyzed formation of pseudouridine (Psi). However, superposition of the representative structures from these four families of enzymes identifies two additional amino acids, a lysine or an arginine (K/R) and a tyrosine (Y), from a K/RxY motif that are structurally conserved in the active site. We have created a series of Thermotoga maritima and Escherichia coli pseudouridine 55 synthase (Psi55S) mutants in which the conserved Y is mutated to other amino acids. A new crystal structure of the T. maritima Psi55S Y67F mutant in complex with a 5FU-RNA at 2.4 A resolution revealed formation of 5-fluoro-6-hydroxypseudouridine (5FhPsi), the same product previously seen in wild-type Psi55S-5FU-RNA complex structures. HPLC analysis confirmed efficient formation of 5FhPsi by both Psi55S Y67F and Y67L mutants but to a much lesser extent by the Y67A mutant when 5FU-RNA substrate was used. However, both HPLC analysis and a tritium release assay indicated that these mutants had no detectable enzymatic activity when the natural RNA substrate was used. The combined structural and mutational studies lead us to propose that the side chain of the conserved tyrosine in these four families of PsiS plays a dual role within the active site, maintaining the structural integrity of the active site through its hydrophobic phenyl ring and acting as a general base through its OH group for the proton abstraction required in the last step of PsiS-catalyzed formation of Psi.

Biochemical and structural studies of A-to-I editing by tRNA:A34 deaminases at the wobble position of transfer RNA.

Initial RNA transcription produces several tRNAs (one in prokaryotes and plant chloroplasts and seven or eight in eukaryotes) that contain an adenosine (A) at the wobble position (position 34). However, in all cases, adenosine at position 34 is post-transcriptionally converted to inosine (I), producing mature tRNAs without adenosine at the wobble position. The enzymes responsible for this A-to-I conversion in tRNA are tadA (acting as a homodimer) in prokaryotes and the heterodimeric ADAT2-ADAT3 complex in eukaryotes. The genes encoding these proteins are essential for cell viability, illustrating the biological importance of A-to-I editing at the wobble position of tRNA. In this study, recombinant tadA proteins from Escherichia coli, Agrobacterium tumefaciens, and Aquifex aeolicus, as well as the ADAT2-ADAT3 proteins from Saccharomyces cerevisiae, were overexpressed in E. coli and purified to homogeneity by chromatography. Crystallization of a proteolytically cleaved A. tumefaciens tadA (missing the last eight amino acids at the C-terminus) produced high-quality crystals, and the structure was determined at 1.6 A resolution. In addition, enzymatic assays of the wild-type proteins as well as several mutants were carried out using both the full-length E. coli tRNA(arg2) and the truncated anticodon stem-loop motif as substrates. Our biochemical and structural studies, in combination with sequence and structural comparisons with other deaminases, allow us to propose a model of tadA-tRNA interaction that explains the molecular basis of tRNA recognition by tadA. In particular, a conserved FFxxxR motif at the C-terminus, which is unique to tadA, has been identified, and its critical role in tRNA substrate recognition is proposed. Furthermore, the structural study of prokaryotic tadA presented here also sheds light on tRNA substrate recognition and the possible evolutionary origin of the eukaryotic ADAT2-ADAT3 heterodimer.

Structural and mutational studies of the catalytic domain of colicin E5: a tRNA-specific ribonuclease.

Colicin E5 specifically cleaves four tRNAs in Escherichia coli that contain the modified nucleotide queuosine (Q) at the wobble position, thereby preventing protein synthesis and ultimately resulting in cell death. Here, the crystal structure of the catalytic domain of colicin E5 (E5-CRD) from E. coli was determined at 1.5 A resolution. Unexpectedly, E5-CRD adopts a core folding with a four-stranded beta-sheet packed against an alpha-helix, seen in the well-studied ribonuclease T1 despite a lack of sequence similarity. Beyond the core catalytic domain, an N-terminal helix, a C-terminal beta-strand and loop, and an extended internal loop constitute an RNA binding cleft. Mutational analysis identified five amino acids that were important for tRNA substrate binding and cleavage by E5-CRD. The structure, together with the mutational study, allows us to propose a model of colicin E5-tRNA interactions, suggesting the molecular basis of tRNA substrate recognition and the mechanism of tRNA cleavage by colicin E5.