The hydrogenation of dicarboxylic acids and their esters in the presence of anilines provides a new synthesis of heterocycles. Ru(acac)
and 1,1,1-tris(diphenylphosphinomethyl)ethane (triphos) gave ...good to excellent yields of the cyclic amines at 220 °C. When aqueous ammonia was used with dimethyl 1,6-hexadienoic acid, ε-caprolactam was obtained in good yield. A side reaction involving alkylation of the amine by methanol was suppressed by using diesters derived from longer chain and branched alcohols. Hydrogenation of optically pure diesters (dimethyl (
)-2-methylbutanedioate and dimethyl (
)-2-methylbutanedioate) with aniline afforded racemic 3-methyl-1-phenylpyrrolidine in 78% yield.
Full text
Available for:
IJS, KILJ, NUK, UL, UM, UPUK
Sepsis remains the leading cause of childhood mortality worldwide. The evolving definition of pediatric sepsis is extrapolated from adult studies. Although lacking formal validation in the pediatric ...population, this working definition has historically proven its clinical utility. Prompt identification of pediatric sepsis is challenging as clinical picture is often variable. Timely intervention is crucial for optimal outcome, thus biomarkers are utilized to aid in immediate, yet judicious, diagnosis of sepsis. Over time, their use in sepsis has expanded with discovery of newer biomarkers that include genomic bio-signatures. Despite recent scientific advances, there is no biomarker that can accurately diagnose sepsis. Furthermore, older biomarkers are readily available in most institutions while newer biomarkers are not. Hence, the latter's clinical value in pediatric sepsis remains theoretical. Albeit promising, scarce data on newer biomarkers have been extracted from research settings making their clinical value unclear. As interest in newer biomarkers continue to proliferate despite their ambiguous clinical use, the literature on older biomarkers in clinical settings continue to diminish. Thus, revisiting the evolving value of these earliest biomarkers in optimizing pediatric sepsis diagnosis is warranted. This review focuses on the four most readily available biomarkers to bedside clinicians in diagnosing pediatric sepsis. IMPACT: The definition of pediatric sepsis remains an extrapolation from adult studies. Older biomarkers that include C-reactive protein, procalcitonin, ferritin, and lactate are the most readily available biomarkers in most pediatric institutions to aid in the diagnosis of pediatric sepsis. Older biomarkers, although in varying levels of reliability, remain to be useful clinical adjuncts in the diagnosis of pediatric sepsis if used in the appropriate clinical context. C-reactive protein and procalcitonin are more sensitive and specific among these older biomarkers in diagnosing pediatric sepsis although evidence varies in different age groups and clinical scenarios.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Single-cell RNA sequencing studies have suggested that total mRNA content correlates with tumor phenotypes. Technical and analytical challenges, however, have so far impeded at-scale pan-cancer ...examination of total mRNA content. Here we present a method to quantify tumor-specific total mRNA expression (TmS) from bulk sequencing data, taking into account tumor transcript proportion, purity and ploidy, which are estimated through transcriptomic/genomic deconvolution. We estimate and validate TmS in 6,590 patient tumors across 15 cancer types, identifying significant inter-tumor variability. Across cancers, high TmS is associated with increased risk of disease progression and death. TmS is influenced by cancer-specific patterns of gene alteration and intra-tumor genetic heterogeneity as well as by pan-cancer trends in metabolic dysregulation. Taken together, our results indicate that measuring cell-type-specific total mRNA expression in tumor cells predicts tumor phenotypes and clinical outcomes.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Less than 5% of children who report penicillin allergy have clinically pertinent type 1 immunoglobulin E mediated hypersensitivity reaction by using direct oral amoxicillin challenge. Several ...pathways have been developed to delabel penicillin allergy by using direct oral amoxicillin challenge, mostly in the outpatient settings, but there is relative scarcity on published outcomes of these pathways, especially in the inpatient pediatric settings.
This study aimed to evaluate the performance of an institutionally derived inpatient penicillin allergy screening tool.
Patients were stratified into three penicillin allergy risk categories by using an institutional screening questionnaire. Patients with a no-risk status were delabeled without challenge testing. Patients with low-risk status underwent direct graded oral amoxicillin challenge and delabeled based on their response. Patients with high-risk status were referred to allergy service.
Ninety-two patients were identified with penicillin allergy. Forty of the 92 patients (43%) were screened. Of the 40 patients screened, 6 (15%) were identified as no risk, 28 (70%) were identified as low risk, and 6 (15%) were identified as high risk. Twenty-four of the 28 patients at low risk (86%) were eligible for direct amoxicillin oral challenge. Seventeen of the 24 (71%) consented to oral challenge but only 12 (71%) underwent direct amoxicillin oral challenge. Eleven of the 12 who underwent oral challenge (92%) were successfully delabeled. Five of the six patients at no risk (83%) were successfully delabeled. Three of the six patients at high risk (50%) were referred for further allergy evaluation. Overall, 16 of the 40 patients screened (40%) were successfully delabeled.
In this small pediatric inpatient study, our institutional risk stratification screening tool identified patients at low risk for penicillin allergy and direct graded oral amoxicillin challenge was safely administered to delabel penicillin allergy in these patients.Clinical trial NCT05020327, <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</ext-link>.
Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure ...refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed.
Case series of patients from the Overcoming COVID-19 public health surveillance registry.
Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021.
Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria for MIS-C or acute COVID-19.
None.
The final cohort included 2,733 patients with MIS-C ( n = 1,530; 37 2.4% requiring ECMO) or acute COVID-19 ( n = 1,203; 71 5.9% requiring ECMO). ECMO patients in both groups were older than those without ECMO support (MIS-C median 15.4 vs 9.9 yr; acute COVID-19 median 15.3 vs 13.6 yr). The body mass index percentile was similar in the MIS-C ECMO versus no ECMO groups (89.9 vs 85.8; p = 0.22) but higher in the COVID-19 ECMO versus no ECMO groups (98.3 vs 96.5; p = 0.03). Patients on ECMO with MIS-C versus COVID-19 were supported more often with venoarterial ECMO (92% vs 41%) for primary cardiac indications (87% vs 23%), had ECMO initiated earlier (median 1 vs 5 d from hospitalization), shorter ECMO courses (median 3.9 vs 14 d), shorter hospital length of stay (median 20 vs 52 d), lower in-hospital mortality (27% vs 37%), and less major morbidity at discharge in survivors (new tracheostomy, oxygen or mechanical ventilation need or neurologic deficit; 0% vs 11%, 0% vs 20%, and 8% vs 15%, respectively). Most patients with MIS-C requiring ECMO support (87%) were admitted during the pre-Delta (variant B.1.617.2) period, while most patients with acute COVID-19 requiring ECMO support (70%) were admitted during the Delta variant period.
ECMO support for SARS-CoV-2-related critical illness was uncommon, but type, initiation, and duration of ECMO use in MIS-C and acute COVID-19 were markedly different. Like pre-pandemic pediatric ECMO cohorts, most patients survived to hospital discharge.
A three‐year‐old boy presented with fever, maculopapular rash involving palms and soles, and hyponatremia two weeks following a tick bite. Empiric doxycycline that he was on was discontinued ...following negative initial rickettsial serology based on the non‐endemicity of Rocky Mountain spotted fever (RMSF) in Northeast Ohio. He demonstrated high inflammatory markers and met the criteria for hemophagocytic lymphohistiocytosis (HLH). With a working diagnosis of macrophage activation syndrome secondary to presumed systemic‐onset juvenile idiopathic arthritis (soJIA), he received HLH‐directed therapy. Rising antibody titers in convalescent sera established the diagnosis of RMSF. The patient recovered completely with HLH directed therapy and re‐institution of doxycycline. This is the first pediatric case report of Rickettsia rickettsii induced HLH demonstrating a favorable outcome despite modified therapy.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The use of 16S rRNA sequencing in culture-negative infections has improved identification of bacterial pathogens in select scenarios, but its clinical impact requires further elucidation, especially ...in the pediatric population. This retrospective study aims to determine the clinical utility of 16S rRNA sequencing on the clinical management of pediatric culture-negative infections in our institution. Significant clinical utility was identified in 30 (40.5%) of 74 clinical samples (
< 0.0001). Of all specimens, pulmonary samples yielded the most clinical utility (
= 9, 30%), followed equally by joint fluid (
= 6, 20%) and bone (
= 6, 20%), with no difference between fluid and fresh tissue specimens (
0.346). Although the difference was not statistically significant (
= 0.4111), the overall use of broad-spectrum coverage was decreased. The median number of antibiotics was decreased from two to one (
< 0.0001) based on 16S rRNA sequencing results. The results suggest that 16S rRNA sequencing has a significant impact on decreasing the number of antibiotics used in the treatment of pediatric culture-negative infections. 16S rRNA sequencing performed on pulmonary specimens has the highest likelihood of identifying a pathogen compared to other specimen types. Additional cost-benefit analysis needs to be completed to further determine clinical benefit.
Using DNA methylation profiles (
= 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised ...clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in
subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.
The hydrogenation of dicarboxylic acids and their esters in the presence of anilines provides a new synthesis of heterocycles. Ru(acac)
3
and 1,1,1-tris(diphenylphosphinomethyl)ethane (triphos) gave ...good to excellent yields of the cyclic amines at 220 °C. When aqueous ammonia was used with dimethyl 1,6-hexadienoic acid, -caprolactam was obtained in good yield. A side reaction involving alkylation of the amine by methanol was suppressed by using diesters derived from longer chain and branched alcohols. Hydrogenation of optically pure diesters (dimethyl (
R
)-2-methylbutanedioate and dimethyl (
S
)-2-methylbutanedioate) with aniline afforded racemic 3-methyl-1-phenylpyrrolidine in 78% yield.
The hydrogenation of dicarboxylic acids and their esters in the presence of anilines provides a new synthesis of heterocycles.
Full text
Available for:
IJS, KILJ, NUK, UL, UM, UPUK
The hydrogenation of dicarboxylic acids and their esters in the presence of anilines provides a new synthesis of heterocycles.
The hydrogenation of dicarboxylic acids and their esters in the presence ...of anilines provides a new synthesis of heterocycles. Ru(acac)
3
and 1,1,1-tris(diphenylphosphinomethyl)ethane (triphos) gave good to excellent yields of the cyclic amines at 220 °C. When aqueous ammonia was used with dimethyl 1,6-hexadienoic acid, ε-caprolactam was obtained in good yield. A side reaction involving alkylation of the amine by methanol was suppressed by using diesters derived from longer chain and branched alcohols. Hydrogenation of optically pure diesters (dimethyl (
R
)-2-methylbutanedioate and dimethyl (
S
)-2-methylbutanedioate) with aniline afforded racemic 3-methyl-1-phenylpyrrolidine in 78% yield.
Full text
Available for:
IJS, KILJ, NUK, UL, UM, UPUK
PDF
