bluuebunny/crossref_metadata_2025 huggingface dataset:
Ligation of the Intersphincteric Fistula Tract and Endorectal Advancement Flap for High Perianal Fistulas in Crohn’s Disease: A Retrospective Cohort Study
Authors: van Praag Elise M , Stellingwerf Merel E , van der Bilt Jarmila D W , Bemelman Wilhelmus A , Gecse Krisztina B , Buskens Christianne J
Published: November 2019

Background and Aims

Ligation of the intersphincteric fistula tract [LIFT] and advancement flap [AF] procedures are well-established, sphincter-preserving procedures for closure of high perianal fistulas. As surgical fistula closure is not commonly offered in Crohn’s disease patients, long-term data are limited. This study aims to evaluate outcomes after LIFT and AF in Crohn’s high perianal fistulas.

Methods

All consecutive Crohn’s disease patients ≥18 years old treated with LIFT or AF between January 2007 and February 2018 were included. The primary outcome was clinical healing and secondary outcomes included radiological healing, recurrence, postoperative incontinence and Vaizey Incontinence Score.

Results

Forty procedures in 37 patients [LIFT: 19, AF: 21, 35.1% male] were included. A non-significant trend was seen towards higher clinical healing percentages after LIFT compared to AF [89.5% vs 60.0%; p = 0.065]. Overall radiological healing rates were lower for both approaches [LIFT 52.6% and AF 47.6%]. Recurrence rates were comparable: 21.1% and 19.0%, respectively. In AF a trend was seen towards higher clinical healing percentages when treated with anti-tumour necrosis factor/immunomodulators [75.0% vs 37.5%; p = 0.104]. Newly developed postoperative incontinence occurred in 15.8% after LIFT and 21.4% after AF. Interestingly, 47.4% of patients had a postoperatively improved Vaizey Score [LIFT: 52.9% and AF: 42.9%]. The mean Vaizey Score decreased from 6.8 [SD 4.8] preoperatively to 5.3 [SD 5.0] postoperatively [p = 0.067].

Conclusions

Both LIFT and AF resulted in satisfactory closure rates in Crohn’s high perianal fistulas. However, a discrepancy between clinical and radiological healing rates was found. Furthermore, almost half of the patients benefitted from surgical intervention with respect to continence.
Modulation of CD39 and Exogenous APT102 Correct Immune Dysfunction in Experimental Colitis and Crohn’s Disease
Authors: Robles René J , Mukherjee Samiran , Vuerich Marta , Xie Anyan , Harshe Rasika , Cowan Peter J , Csizmadia Eva , Wu Yan , Moss Alan C , Chen Ridong , Robson Simon C , Longhi Maria Serena
Published: November 2019

Background and Aims

CD39/ENTPD1 scavenges pro-inflammatory nucleotides, to ultimately generate immunosuppressive adenosine, which has a central role in immune homeostasis. Global deletion of Cd39 increases susceptibility to experimental colitis while single nucleotide polymorphisms within the human CD39 promoter, and aberrant patterns of expression during experimental hypoxia, predispose to Crohn’s disease. We aimed to define the impact of transgenic human CD39 [hTG] overexpression in experimental colitis and to model therapeutic effects using the recombinant apyrase APT102 in vivo. We also determined the in vitro effects of APT102 on phenotypic and functional properties of regulatory T-lymphocytes derived from patients with Crohn’s disease.

Methods

Colitis was induced by administration of dextran sulfate sodium in wild-type [WT] or hTG mice, and, in another model, by adoptive transfer of CD45RBhigh cells with or without WT or hTG regulatory T cells [Treg]. In additional experiments, mice were treated with APT102. The effects of APT102 on phenotype and function of Treg and type-1 regulatory T [Tr1] cells were also evaluated, after purification from peripheral blood and lamina propria of Crohn’s disease patients [n = 38].

Results

Overexpression of human CD39 attenuated experimental colitis and protected from the deleterious effects of systemic hypoxia, pharmacologically induced by deferoxamine. Administration of APT102 in vivo enhanced the beneficial effects of endogenous Cd39 boosted by the administration of the aryl hydrocarbon receptor [AhR] ligand unconjugated bilirubin [UCB]. Importantly, supplemental APT102 restored responsiveness to AhR stimulation by UCB in Treg and Tr1 cells, obtained from Crohn’s disease patients.

Conclusions

hCD39 overexpression ameliorated experimental colitis and prevented hypoxia-related damage in vivo. Exogenous administration of APT102 boosted AhR-mediated regulatory effects in vivo while enhancing Treg functions in Crohn’s disease in vitro.
Patient trends and outcomes of surgery for type A acute aortic dissection in Japan: an analysis of more than 10 000 patients from the Japan Cardiovascular Surgery Database
Authors: Abe Tomonobu , Yamamoto Hiroyuki , Miyata Hiroaki , Motomura Noboru , Tokuda Yoshiyuki , Tanemoto Kazuo , Usui Akihiro , Takamoto Shinichi
Published: November 2019

OBJECTIVES

To evaluate the background trends and surgical outcomes for more than 10 000 patients with acute type A dissection in Japan in a recent 8-year period.

METHODS

Data on replacement of the ascending aorta and/or aortic arch for acute type A dissection were collected from the Japan Cardiovascular Surgery Database from 2008 to 2015. Linear-by-linear association tests or Cuzick’s test for trend was used to evaluate group trends over time. The results were calculated for ascending or hemiarch replacement and arch replacement. A multivariable logistic regression model was used to calculate the risk-adjusted operative mortality rate.

RESULTS

A total of 11 843 patients were included. The overall 30-day mortality and operative mortality rates were 7.6% and 9.5%, respectively. The number of surgically treated cases increased from 2436 patients in 2008–2009 to 3533 in 2014–2015, a 45.0% increase. A trend analysis revealed significant changes in patient characteristics with time, including increasing age and rate of preoperative renal failure. Despite worsening risk factors, the unadjusted operative mortality rate with arch replacement showed a significant downward trend (P = 0.01; test of trend). The risk-adjusted mortality rate showed a downward trend both in ascending aorta or hemiarch replacement and arch replacement, although the trend was not statistically significant (P > 0.05).

CONCLUSIONS

Unadjusted and adjusted operative deaths have shown a decreasing trend, although patients undergoing surgery for acute type A dissection have demonstrated worsening of risk factors, such as age and renal failure. The number of surgeries performed for acute type A dissection significantly increased throughout the study period in Japan.
Convergent Evolution of Claw Shape in a Transcontinental Lizard Radiation
Authors: Baeckens Simon , Goeyers Charlotte , Van Damme Raoul
Published: November 2019

Species occupying similar selective environments often share similar phenotypes as the result of natural selection. Recent discoveries, however, have led to the understanding that phenotypes may also converge for other reasons than recurring selection. We argue that the vertebrate claw system constitutes a promising but understudied model system for testing the adaptive nature of phenotypic, functional, and genetic convergence. In this study, we combine basic morphometrics and advanced techniques in form analysis to examine claw shape divergence in a transcontinental lizard radiation (Lacertidae). We find substantial interspecific variation in claw morphology and phylogenetic comparative statistics reveal a strong correlation with structural habitat use: ground-dwelling species living in open areas are equipped with long, thick, weakly curved, slender-bodied claws, whereas climbing species carry high, short, strongly curved, full-bodied claws. Species occupying densely vegetated habitats tend to carry intermediately shaped claws. Evolutionary models suggest that claw shape evolves toward multiple adaptive peaks, with structural habitat use pulling species toward a specific selective optimum. Contrary to findings in several other vertebrate taxa, our analyses indicate that environmental pressures, not phylogenetic relatedness, drive convergent evolution of similarly shaped claws in lacertids. Overall, our study suggests that lacertids independently evolved similarly shaped claws as an adaptation to similar structural environments in order to cope with the specific locomotory challenges posed by the habitat. Future biomechanical studies that link form and function in combination with genomic and development research will prove valuable in better understanding the adaptive significance of claw shape divergence.
Phase harmonic correlations and convolutional neural networks
Authors: Mallat Stéphane , Zhang Sixin , Rochette Gaspar
Published: November 2019

A major issue in harmonic analysis is to capture the phase dependence of frequency representations, which carries important signal properties. It seems that convolutional neural networks have found a way. Over time-series and images, convolutional networks often learn a first layer of filters that are well localized in the frequency domain, with different phases. We show that a rectifier then acts as a filter on the phase of the resulting coefficients. It computes signal descriptors that are local in space, frequency and phase. The nonlinear phase filter becomes a multiplicative operator over phase harmonics computed with a Fourier transform along the phase. We prove that it defines a bi-Lipschitz and invertible representation. The correlations of phase harmonics coefficients characterize coherent structures from their phase dependence across frequencies. For wavelet filters, we show numerically that signals having sparse wavelet coefficients can be recovered from few phase harmonic correlations, which provide a compressive representation.
Reduced Cardiac Index Reserve and Hypovolemia in Severe Falciparum Malaria
Authors: Kingston Hugh W F , Ghose Aniruddha , Rungpradubvong Voravut , Satitthummanid Sudarat , Herdman M Trent , Plewes Katherine , Leopold Stije J , Ishioka Haruhiko , Mohanty Sanjib , Maude Richard J , Schultz Marcus J , Lagrand Wim K , Hossain Md Amir , Day Nicholas P J , White Nicholas J , Anstey Nicholas M , Dondorp Arjen M
Published: November 2019

Background

Impaired microvascular perfusion is central to the development of coma and lactic acidosis in severe falciparum malaria. Refractory hypotension is rare on admission but develops frequently in fatal cases. We assessed cardiac function and volume status in severe falciparum malaria and its prognostic significance.

Methods

Patients with severe (N = 101) or acute uncomplicated falciparum malaria (N = 83) were recruited from 2 hospitals in India and Bangladesh, and healthy participants (N = 44) underwent echocardiography.

Results

Patients with severe malaria had 38% shorter left ventricular (LV) filling times and 25% shorter LV ejection times than healthy participants because of tachycardia; however, stroke volume, LV internal diameter in diastole (LVIDd), and LV internal diameter in systole (LVIDs) indices were similar. A low endocardial fraction shortening (eFS) was present in 17% (9 of 52) of severe malaria patients. Adjusting for preload and afterload, eFS was similar in health and severe malaria. Fatal cases had smaller baseline LVIDd and LVIDs indices, more collapsible inferior vena cavae (IVC), and higher heart rates than survivors. The LVIDs and IVC collapsibility were independent predictors for mortality, together with base excess and Glasgow Coma Scale.

Conclusions

Patients with severe malaria have rapid ejection of a normal stroke volume. Fatal cases had features of relative hypovolemia and reduced cardiac index reserve.
Towards Rapid Sepsis Diagnosis and Patients Stratification: What’s New From Microbiology and Omics Science
Authors: Mangioni Davide , Peri Anna Maria , Rossolini Gian Maria , Viaggi Bruno , Perno Carlo Federico , Gori Andrea , Bandera Alessandra
Published: November 2019

Early etiological diagnosis and characterization of host response to infection are becoming central in sepsis recognition and management. Still, limitations in conventional diagnosis and patient stratification contribute to the high mortality rates of septic patients despite new antimicrobials and resuscitation agents. Novel microbiological techniques and omics analyses have recently led to the development of several tests that are now commercially available or in the pipeline as rapid diagnostic tools. In this review, we first summarize emerging assays for the etiological diagnosis starting directly from whole blood, based on target-specific PCRs or metagenomics. We then investigate results of different omics approaches for both bedside diagnosis of immune dysfunction and detection of patients’ signatures associated with different clinical outcomes or potential response to individualized therapies. Finally, we discuss about the translation of these novel laboratory tools into clinical practice, showing how their best performance is achieved when integrated within antimicrobial stewardship programs.
Measles Outbreak in a High-Income Country: Are Pediatricians Ready?
Authors: Lo Vecchio Andrea , Montagnani Carlotta , Krzysztofiak Andrzej , Valentini Piero , Rossi Nadia , Bozzola Elena , Castelli Gattinara Guido , Magurano Fabio , Guarino Alfredo , Galli Luisa ,   Italian Society for Pediatric Infectious Diseases Measles Study Group, Silvia Garazzino , Irene Raffaldi , Maria Di Gangi , Susanna Esposito , Barbara Vecchi , Luisa Melzi Maria , Marcello Lanari , Giorgio Zavarise , Samantha Bosis , Mariella Valenzise , Salvatore Cazzato , Michele Sacco , Maria Rita Govoni , Elena Mozzo , Maria Donata Cambriglia , Pata Davide , Graziosi Alessandro , Sala Debora , Baggieri Melissa
Published: November 2019

Background

Measles is a highly communicable infection with potentially severe complications. It is rarely reported in high-income countries and the limited awareness and experience of pediatricians may result in misdiagnosis. The present study aimed at investigating physician’s ability and timing to reach diagnosis during a recent outbreak in Italy.

Methods

The Italian Society for Pediatric Infectious Diseases conducted a retrospective, multicenter study in children hospitalized for measles between 1 January 2016 and 30 August 2017 in secondary and tertiary care hospitals. The appropriateness of diagnosis at admission, the time to reach clinical diagnosis, and serological confirmation of measles were recorded.

Results

At hospital admission, measles was misdiagnosed in 101 (40.5%) of the 249 children (median age, 14.5 months) enrolled. The appropriate diagnosis increased from 30% to 72.5% during the period of observation (P < .001). A greater chance of receiving an appropriate diagnosis was demonstrated in children who reported a contact with measles (odds ratio [OR], 5.2; 95% confidence interval [CI], 3.0–9.2) or in those seen in institutions that managed more cases (OR, 7.39; 95% CI, 3.22–16.9; P = .0001). In contrast, children with underlying chronic conditions had a higher risk of misdiagnosis (appropriate diagnosis OR, 0.19; 95% CI, 0.10–0.33). The mean time from the onset of symptoms to clinical diagnosis was 4.55 ± 2.2 days and to serological confirmation was 7.0 ± 3.4 days.

Conclusions

Measles is frequently misdiagnosed in low-prevalence settings. Specific measures to increase pediatricians’ awareness about vaccine-preventable infections need to be implemented.
Long troughs in the Lyman-α forest below redshift 6 due to islands of neutral hydrogen
Authors: Keating Laura C , Weinberger Lewis H , Kulkarni Girish , Haehnelt Martin G , Chardin Jonathan , Aubert Dominique
Published: November 2019

A long (110 cMpc h−1) and deep absorption trough in the Ly α forest has been observed extending down to redshift 5.5 in the spectrum of ULAS J0148+0600. Although no Ly α transmission is detected, Ly β spikes are present which has led to claims that the gas along this trough must be ionized. Using high-resolution cosmological radiative transfer simulations in large volumes, we show that in a scenario where reionization ends late (z ∼ 5.2), our simulations can reproduce troughs as long as observed. In this model, we find that the troughs are caused by islands of neutral hydrogen. Small ionized holes within the neutral islands allow for the transmission of Ly β. We have also modelled the Ly α emitter population around the simulated troughs, and show that there is a deficit of Ly α emitters close to the trough as is observed.
iPTF14hls as a variable hyper-wind from a very massive star
Authors: Moriya Takashi J , Mazzali Paolo A , Pian Elena
Published: November 2019

The origin of iPTF14hls, which had Type IIP supernova-like spectra but kept bright for almost two years with little spectral evolution, is still unclear. We here propose that iPTF14hls was not a sudden outburst like supernovae but rather a long-term outflow similar to stellar winds. The properties of iPTF14hls, which are at odds with a supernova scenario, become natural when interpreted as a stellar wind with variable mass-loss rate. Based on the wind hypothesis, we estimate the mass-loss rates of iPTF14hls in the bright phase. We find that the instantaneous mass-loss rate of iPTF14hls during the 2-year bright phase was more than a few M⊙ yr−1 (“hyper-wind”) and it reached as much as 10 M⊙ yr−1 . The total mass lost over two years was about 10 M⊙. Interestingly, we find that the light curve of iPTF14hls has a very similar shape to that of η Carinae during the Great Eruption, which also experienced a similar but less extreme brightening accompanied by extraordinary mass loss, shedding more than 10 M⊙ in 10 years. The progenitor of iPTF14hls is less than 150 M⊙ if it still exists, which is similar to η Carinae. The two phenomena may be related to a continuum-driven extreme wind from very massive stars.
What determines the observational magnitudes of Forbush events on Earth: A critique of the traditional manual method
Authors: Okike O
Published: November 2019

Forbush decreases (FDs) seem to be the compass for researchers searching for Sun–Earth weather relationships. Thus, a wide range of the solar-terrestrial literature is dominated by FD-based analyses. While the results of such investigations are often questioned on the basis of small FD sample sizes, statistical significance tests and inappropriate methodological approaches, the efficiency and the validity of manual FD event selection are yet to be examined in detail. Because the results obtained depend on the Forbush event location on Earth, and on timing and magnitude estimation, this paper emphasizes the need for the correct acquisition of FD data prior to composition or correlation/regression analyses.
A Burst of Genetic Innovation in Drosophila Actin-Related Proteins for Testis-Specific Function
Authors: Schroeder Courtney M , Valenzuela John R , Mejia Natividad Isabel , Hocky Glen M , Malik Harmit S
Published: November 2019

Many cytoskeletal proteins perform fundamental biological processes and are evolutionarily ancient. For example, the superfamily of actin-related proteins (Arps) specialized early in eukaryotic evolution for diverse cellular roles in the cytoplasm and the nucleus. Despite its strict conservation across eukaryotes, we find that the Arp superfamily has undergone dramatic lineage-specific diversification in Drosophila. Our phylogenomic analyses reveal four independent Arp gene duplications that occurred in the common ancestor of the obscura group of Drosophila and have been mostly preserved in this lineage. All four obscura-specific Arp paralogs are predominantly expressed in the male germline and have evolved under positive selection. We focus our analyses on the divergent Arp2D paralog, which arose via a retroduplication event from Arp2, a component of the Arp2/3 complex that polymerizes branched actin networks. Computational modeling analyses suggest that Arp2D can replace Arp2 in the Arp2/3 complex and bind actin monomers. Together with the signature of positive selection, our findings suggest that Arp2D may augment Arp2’s functions in the male germline. Indeed, we find that Arp2D is expressed during and following male meiosis, where it localizes to distinct locations such as actin cones—specialized cytoskeletal structures that separate bundled spermatids into individual mature sperm. We hypothesize that this unprecedented burst of genetic innovation in cytoskeletal proteins may have been driven by the evolution of sperm heteromorphism in the obscura group of Drosophila.
Exploring the interactions of short RNAs with the human 40S ribosomal subunit near the mRNA entry site by EPR spectroscopy
Authors: Malygin Alexey A , Krumkacheva Olesya A , Graifer Dmitri M , Timofeev Ivan O , Ochkasova Anastasia S , Meschaninova Maria I , Venyaminova Alya G , Fedin Matvey V , Bowman Michael , Karpova Galina G , Bagryanskaya Elena G
Published: November 2019

The features of previously unexplored labile complexes of human 40S ribosomal subunits with RNAs, whose formation is manifested in the cross-linking of aldehyde derivatives of RNAs to the ribosomal protein uS3 through its peptide 55–64 located outside the mRNA channel, were studied by EPR spectroscopy methods. Analysis of subatomic 40S subunit models showed that a likely site for labile RNA binding is a cluster of positively charged amino acid residues between the mRNA entry site and uS3 peptide 55–64. This is consistent with our finding that the 3′-terminal mRNA fragment hanging outside the 40S subunit prevents the cross-linking of an RNA derivative to this peptide. To detect labile complexes of 40S subunits with RNA by DEER/PELDOR spectroscopy, an undecaribonucleotide derivative with nitroxide spin labels at terminal nucleotides was utilized. We demonstrated that the 40S subunit channel occupancy with mRNA does not affect the RNA derivative binding and that uS3 peptide 55–64 is not involved in binding interactions. Replacing the RNA derivative with a DNA one revealed the importance of ribose 2′-OH groups for the complex formation. Using the single-label RNA derivatives, the distance between the mRNA entry site and the loosely bound RNA site on the 40S subunit was estimated.
Systematic sequencing of chloroplast transcript termini from Arabidopsis thaliana reveals >200 transcription initiation sites and the extensive imprints of RNA-binding proteins and secondary structures
Authors: Castandet Benoît , Germain Arnaud , Hotto Amber M , Stern David B
Published: November 2019

Chloroplast transcription requires numerous quality control steps to generate the complex but selective mixture of accumulating RNAs. To gain insight into how this RNA diversity is achieved and regulated, we systematically mapped transcript ends by developing a protocol called Terminome-seq. Using Arabidopsis thaliana as a model, we catalogued >215 primary 5′ ends corresponding to transcription start sites (TSS), as well as 1628 processed 5′ ends and 1299 3′ ends. While most termini were found in intergenic regions, numerous abundant termini were also found within coding regions and introns, including several major TSS at unexpected locations. A consistent feature was the clustering of both 5′ and 3′ ends, contrasting with the prevailing description of discrete 5′ termini, suggesting an imprecision of the transcription and/or RNA processing machinery. Numerous termini correlated with the extremities of small RNA footprints or predicted stem-loop structures, in agreement with the model of passive RNA protection. Terminome-seq was also implemented for pnp1–1, a mutant lacking the processing enzyme polynucleotide phosphorylase. Nearly 2000 termini were altered in pnp1–1, revealing a dominant role in shaping the transcriptome. In summary, Terminome-seq permits precise delineation of the roles and regulation of the many factors involved in organellar transcriptome quality control.
Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites
Authors: Hammam Elie , Ananda Guruprasad , Sinha Ameya , Scheidig-Benatar Christine , Bohec Mylene , Preiser Peter R , Dedon Peter C , Scherf Artur , Vembar Shruthi S
Published: November 2019

DNA cytosine modifications are key epigenetic regulators of cellular processes in mammalian cells, with their misregulation leading to varied disease states. In the human malaria parasite Plasmodium falciparum, a unicellular eukaryotic pathogen, little is known about the predominant cytosine modifications, cytosine methylation (5mC) and hydroxymethylation (5hmC). Here, we report the first identification of a hydroxymethylcytosine-like (5hmC-like) modification in P. falciparum asexual blood stages using a suite of biochemical methods. In contrast to mammalian cells, we report 5hmC-like levels in the P. falciparum genome of 0.2–0.4%, which are significantly higher than the methylated cytosine (mC) levels of 0.01–0.05%. Immunoprecipitation of hydroxymethylated DNA followed by next generation sequencing (hmeDIP-seq) revealed that 5hmC-like modifications are enriched in gene bodies with minimal dynamic changes during asexual development. Moreover, levels of the 5hmC-like base in gene bodies positively correlated to transcript levels, with more than 2000 genes stably marked with this modification throughout asexual development. Our work highlights the existence of a new predominant cytosine DNA modification pathway in P. falciparum and opens up exciting avenues for gene regulation research and the development of antimalarials.
Sex hormone-binding globulin levels are inversely associated with nonalcoholic fatty liver disease in HIV-infected and –uninfected men
Authors: Price Jennifer C , Wang Ruibin , Seaberg Eric C , Brown Todd T , Budoff Matthew J , Kingsley Lawrence A , Palella Frank J , Witt Mallory D , Post Wendy S , Lake Jordan E , Thio Chloe L
Published: November 2019

Background

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. Elevated sex hormone-binding globulin (SHBG) levels have been observed in the setting of HIV and may protect against some metabolic disorders. We aimed to investigate whether higher SHBG levels may protect against NAFLD in men with/without HIV.

Methods

NAFLD was assessed using non-contrast CT in 530 men in the Multicenter AIDS Cohort Study (MACS) who drank <3 alcoholic drinks/day and were uninfected with chronic hepatitis C or B (340HIV+,190HIV-). Morning serum samples were tested for SHBG, total testosterone (TT), and adiponectin. Multivariable logistic regression was used to assess associations between HIV, SHBG, TT, adiponectin and NAFLD.

Results

Median SHBG was highest among HIV+/NAFLD- men and lowest among HIV-/NAFLD+ men. Adjusted for demographics, HIV, visceral adiposity, HOMA-IR, TT, and PNPLA3 genotype, higher SHBG was associated with lower odds of NAFLD [odds ratio(OR) 0.52 per doubling,95% confidence interval(CI) 0.34-0.80]. In separate multivariable models without SHBG, HIV (OR 0.46,95%CI 0.26-0.79) and higher adiponectin (OR 0.66 per doubling,95%CI 0.49-0.89) were associated with lower NAFLD odds, whereas TT was not significantly associated (OR 0.74 per doubling,95%CI 0.53-1.04). Adjusting for SHBG attenuated the associations of HIV (OR 0.61,95%CI 0.34-1.08) and adiponectin (OR 0.74,95%CI 0.54-1.02) with NAFLD.

Conclusions

SHBG levels were higher among HIV+ men, independently associated with lower NAFLD, and could partially explain the associations of HIV and higher adiponectin with lower NAFLD in our cohort. These findings suggest that SHBG may protect against NAFLD, supporting further prospective and mechanistic studies.
The differential characteristics between severe fever with thrombocytopenia syndrome and hemorrhagic fever with renal syndrome in the endemic regions
Authors: Lu Qing-Bin , Li Hao , Jiang Fa-Chun , Mao Ling-Ling , Liu Xue-Sheng , Wang Ning , Zhou Yong-Yun , Dai Ke , Yang Zhen-Dong , Dong Li-Yan , Cui Ning , Zhang Xiao-Ai , Zhang Shao-Fei , Zhang Pan-He , Fang Li-Qun , Liu Wei
Published: November 2019

The misdiagnosis between severe fever with thrombocytopenia syndrome and hemorrhagic fever with renal syndrome were identified in endemic regions for both diseases. A model based on age, mouse/tick contact in recent one month, clinical characteristics including blush, low back pain, diarrhea, enlarged lymph nodes, and white blood cell count, yielded a high area under the curve of 0.985 (95% confidence interval, 0.979-0.992), enabling an effective differentiation between two diseases.
Rapid Multiplex Testing for Upper Respiratory Pathogens in the Emergency Department: A Randomized Controlled Trial
Authors: May Larissa , Tatro Grant , Poltavskiy Eduard , Mooso Benjamin , Hon Simson , Bang Heejung , Polage Christopher
Published: November 2019

Background

Acute upper respiratory tract infections are a common cause of Emergency Department (ED) visits and often result in unnecessary antibiotic treatment. 

Methods

We conducted a randomized clinical trial to evaluate the impact of a rapid, multi-pathogen respiratory panel (RP) test versus usual care (control). Patients were eligible if they were ≥12 months old, had symptoms of upper respiratory infection or influenza like illness, and were not on antibiotics. The primary outcome was antibiotic prescription; secondary outcomes included antiviral prescription, disposition, and length of stay (ClinicalTrials.gov# NCT02957136).

Results

Of 191 patients enrolled, 93 (49%) received RP testing; 98 (51%) received usual care. Fifty-three (57%) RP and 7 (7%) control patients had a virus detected and reported during the ED visit (p=0.0001). Twenty (22%) RP patients and 33 (34%) usual care patients received antibiotics during the ED visit (-12% [95% CI -25%, 0.4%]; p=0.06/0.08); 9 RP patients received antibiotics despite having a virus detected. The magnitude of antibiotic reduction was greater in children (-19%) versus adults (-9%; post-hoc analysis). There was no difference in antiviral use, length of stay, or disposition.

Conclusions

Rapid RP testing was associated with a trend towards decreased antibiotic use, suggesting a potential benefit from more rapid viral tests in the ED. Future studies should determine if specific groups are more likely to benefit from testing and evaluate relative cost and effectiveness of broad testing, focused testing, and a combined diagnostic and antimicrobial stewardship approach.
FAM19A1, a brain‐enriched and metabolically responsive neurokine, regulates food intake patterns and mouse behaviors
Authors: Lei Xia , Liu Lili , Terrillion Chantelle E. , Karuppagounder Senthilkumar S. , Cisternas Pedro , Lay Mark , Martinelli David C. , Aja Susan , Dong Xinzhong , Pletnikov Mikhail V. , Wong G. William
Published: November 2019

Cytokines and chemokines play diverse roles in different organ systems. Family with sequence similarity 19, member A1‐5 (FAM19A1‐A5; also known as TAFA1‐5) is a group of conserved chemokine‐like proteins enriched in the CNS of mice and humans. Their functions are only beginning to emerge. Here, we show that the expression of Fam19a1‐a5 in different mouse brain regions are induced or suppressed by unfed and refed states. The striking nutritional regulation of Fam19a family members in the brain suggests a potential central role in regulating metabolism. Using a knockout (KO) mouse model, we show that loss of FAM19A1 results in sexually dimorphic phenotypes. In male mice, FAM19A1 deficiency alters food intake patterns during the light and dark cycle. Fam19a1 KO mice are hyperactive, and locomotor hyperactivity is more pronounced in female KO mice. Behavior tests indicate that Fam19a1 KO female mice have reduced anxiety and sensitivity to pain. Spatial learning and exploration, however, is preserved in Fam19a1 KO mice. Altered behaviors are associated with elevated norepinephrine and dopamine turnover in the striatum. Our results establish an in vivo function of FAM19A1 and highlight central roles for this family of neurokines in modulating animal physiology and behavior.—Lei, X., Liu, L., Terrillion, C. E., Karuppagounder, S. S., Cisternas, P., Lay, M., Martinelli, D. C., Aja, S., Dong, X., Pletnikov, M. V., Wong, G. W. FAM19A1, a brain‐enriched and metabolically responsive neurokine, regulates food intake patterns and mouse behaviors. FASEB J. 33, 14734‐14747 (2019). www.fasebj.org
Mechanisms of allergy and adult asthma
Authors: Chen Xuesong , Corry David B. , Li Evan
Published: November 2019

Purpose of review

Allergic asthma reflects the interplay between inflammatory mediators and immune, airway epithelial, and other cells. This review summarizes key insights in these areas over the past year.

Recent findings

Key findings over the past year demonstrate that epithelial cells mediate tight junction breakdown to facilitate the development of asthma-like disease in mice. Innate lymph lymphoid cells (ILC), while previously shown to promote allergic airway disease, have now been shown to inhibit the development of severe allergic disease in mice. Fibrinogen cleavage products (previously shown to mediate allergic airway disease and macrophage fungistatic immunity by signaling through Toll-like receptor 4) have now been shown to first bind to the integrin Mac-1 (CD11c/CD18). Therapeutically, recent discoveries include the development of the antiasthma drug PM-43I that inhibits the allergy-related transcription factors STAT5 and STAT6 in mice, and confirmatory evidence of the efficacy of the antifungal agent voriconazole in human asthma.

Studies over the past year provide critical new insight into the mechanisms by which epithelial cells, ILC, and coagulation factors contribute to the expression of asthma-like disease and further support the development antiasthma drugs that block STAT factors and inhibit fungal growth in the airways.
Anesthetic management of lung transplantation: impact of presenting disease
Authors: Martin Archer Kilbourne , Fritz Ashley V. , Wilkey Barbara J.
Published: November 2019

Purpose of review

Recent literature has described the emerging role of anesthesiologists as key members of the lung transplantation team and the impact of anesthetic management on outcomes. This review examines the impact of presenting cause of end-stage lung disease (ESLD) on anesthetic management.

Recent findings

The four primary causes of ESLD are suppurative, obstructive, or restrictive processes, and pulmonary hypertension. Our recent review of perioperative literature revealed new data regarding preoperative risk stratification, intraoperative management, and postoperative use of extracorporeal membrane oxygenation (ECMO) support. Major studies specifically about anesthetic management are lacking; however, the principles studied are readily applicable to the design of a perioperative care plan. The most compelling data have resulted in a revolutionary change in terms of intraoperative support and postoperative planning for pulmonary hypertension patients. Historically treated with cardiopulmonary bypass, significant data have been reported describing the successful use of ECMO both as an intraoperative support with superior outcomes, as well as postoperative support for improved stability during biventricular remodeling post graft implantation.

The application of these updated findings should assist anesthesiologists as they develop internal protocols and external guidelines to integrate within multidisciplinary teams caring for the lung transplant patient.
Validity of Self-reported Cannabis Use Among Pregnant Females in Northern California
Authors: Young-Wolff Kelly C. , Sarovar Varada , Tucker Lue-Yen , Goler Nancy , Conway Amy , Weisner Constance , Armstrong Mary Anne , Alexeeff Stacey
Published: November 2019

Background:

Most clinical and epidemiologic estimates of prenatal cannabis use are based on self-report, and the validity of self-reported cannabis use has not been examined in a large, representative population of pregnant women. We determined the validity of self-reported prenatal cannabis use and predictors of nondisclosure using data from Kaiser Permanente Northern California's (KPNC) healthcare system with universal prenatal cannabis screening during prenatal care.

Methods:

Validation study using data from 281,025 pregnancies in KPNC among females aged ≥11 years who completed a self-administered questionnaire on prenatal cannabis use and a cannabis urine toxicology test from 2009 to 2017. We calculated sensitivity, specificity, positive predictive value, and negative predictive value of self-reported prenatal cannabis use using urine toxicology testing as the criterion standard, and sensitivity of urine toxicology testing using self-reported use as the criterion standard. We compared sociodemographics of those who disclosed versus did not disclose prenatal cannabis use.

Results:

Urine toxicology testing identified more instances of prenatal cannabis use than self-report (4.9% vs 2.5%). Sensitivity of self-reported use was low (33.9%). Sensitivity of the toxicology test was higher (65.8%), with greater detection of self-reported daily (83.9%) and weekly (77.4%) than monthly or less use (54.1%). Older women, those of Hispanic race/ethnicity, and those with lower median neighborhood incomes were most likely to be misclassified as not using cannabis by self-reported screening.

Conclusions:

Given that many women choose not to disclose prenatal cannabis use, clinicians should educate all prenatal patients about the potential risks and advise them to quit cannabis use during pregnancy.
Supporting the Use of Medications for Addiction Treatment in US Drug Courts: Opportunities for Health Professionals
Authors: Morris Nathaniel P. , Bentzley Brandon S.
Published: November 2019

Drug courts are specialty courts that offer treatment services as alternatives to incarceration for defendants struggling with problems related to substance use. These courts have become major access points in the United States for the treatment of substance use disorders, but drug court participants often have limited access to medications for addiction treatment (MAT). A growing chorus of advocates and organizations have called for expanding access to MAT in drug courts, and health professionals may wonder how to join in these efforts. This article reviews practical ways in which individual health professionals might support access to MAT in drug courts, including working with drug courts, fighting public stigma against MAT, contributing to research on MAT in drug courts, and expanding addiction training among clinicians.
Local treatment of stage IIIA-N2 nonsmall cell lung cancer: surgery and/or radiotherapy
Authors: Van Meerbeeck Jan P. , De Pooter Christel , Raskin Jo , Janssens Annelies , Van Schil Paul EY
Published: November 2019

Purpose of review

Controversy exists regarding the optimal treatment of patients with stage IIIA-N2 nonsmall cell lung cancer because of its heterogeneity. Patients are at risk for both local and distant disease relapse after primary local treatment. However, there may be a window of opportunity for surgery, if mediastinal downstaging has been obtained after induction therapy. This manuscript reviews the outcome of patients treated by neo-adjuvant chemotherapy (NA-C) followed by surgery, compared with patients treated with either definitive sequential or concurrent chemoradiotherapy (cCRT), illustrated by a single-centre retrospective case series.

Recent findings

Of 53 eligible patients, 19 received NA-C and underwent surgical resection, whilst 20 and 14 received concurrent or sequential definitive CRT, respectively. A significant difference in progression-free survival favouring NA-C followed by surgery over both CRT modalities was found. However, this translated only in an overall survival benefit in comparison with sequential definitive CRT. A trend for better outcome was observed in selected surgical patients with single-level mediastinal involvement and complete resection.

Our case series results are consistent with the present standard of care of CRT, which restricts surgical resection to carefully selected patients. Immunotherapy will likely change the treatment paradigm.
Cerebral and peripheral vascular differences between pre- and postmenopausal women
Authors: Brislane Áine , Low David A. , Carter Sophie E. , Holder Sophie M. , Jones Helen , Hopkins Nicola D.
Published: November 2019

Objective:

Menopause is associated with lower peripheral vascular function; however, cerebrovascular responses to this time-period are unclear. We aimed to describe peripheral vascular and cerebrovascular differences between pre- and postmenopausal women.

Methods:

Fifty pre- and postmenopausal women (N = 100) underwent assessments of cerebral blood flow; cerebrovascular reactivity and autoregulation; carotid artery reactivity; brachial and femoral artery flow-mediated dilation; and carotid, brachial, and femoral artery intima-media thickness. Comparisons were made between pre- and postmenopausal women followed by a secondary analysis (N = 20) between late premenopausal women and those within 5 years of menopause using a general linear model.

Results:

Cerebral blood flow (−11 [−17, −4 cm/s]; P = 0.03) and carotid reactivity (−2.3 [−4.3, −0.3%] P = 0.03) were lower postmenopause compared to premenopause, whereas cerebrovascular reactivity and autoregulation did not differ (P > 0.05). Postmenopausal women had a larger carotid (0.16 [0.13, 0.20 mm] P < 0.001), brachial (0.07 [0.03, 0.11 mm] P = 0.004), and femoral artery intima-media thickness (0.09 [0.05, 0.14 mm] P = 0.04), alongside lower brachial (−2.3 [−3.9, −0.7%] P = 0.004) and femoral artery flow-mediated dilation (−3.0 [−4.3, −1.8%] P < 0.001). In the secondary-analysis, early postmenopausal women had a lower femoral artery flow-mediated dilation (−1.9 [−3.9, −0.0%] P = 0.05) and larger carotid intima-media thickness (0.07 [0.00, 0.14 mm] P = 0.03) compared to late premenopausal women.

Conclusions:

Cerebral blood flow, carotid artery reactivity, peripheral vascular function, and structure are negatively affected by age. Preliminary data indicate that femoral artery function and carotid artery structure may be potentially impaired in early postmenopause compared with late premenopause. These findings suggest that conduit arteries susceptible to atherosclerosis may be important targets for lifestyle intervention in early menopause.
Ethical Considerations in Chronic Brain Injury
Authors: Hawley Lenore , Hammond Flora M. , Cogan Alison M. , Juengst Shannon , Mumbower Rachael , Pappadis Monique R. , Waldman Wendy , Dams-O'Connor Kristen
Published: November 2019

A growing number of individuals are living with chronic traumatic brain injury. As these individuals and their families attempt to reintegrate into their communities, several ethical questions arise for clinicians and researchers. These include issues around alignment of perspectives and priorities, as well as responsibilities for ongoing treatment, education, community outreach, and research. An action plan for addressing these questions is outlined.
Congenital afibrinogenemia in a patient with vascular abnormalities and a novel variant: clinical-molecular description and literature review
Authors: Virmond Luiza A. , Micheletti Cecilia , Pinto Christiane M.S. , Soares Maria F.F. , Milanezi Fernanda , Nakano Viviane , Perrone Eduardo
Published: November 2019

The objective is to report a patient with congenital afibrinogenemia and vascular abnormalities and also review the clinical and molecular issues. The female proband, diagnosed with congenital afibrinogenemia, was admitted at a hospital due to a hemorrhagic shock. Angiotomography revealed ectasias from ascending branch to the abdominal aorta, with multiple calcifications and atheroma. Clinical exome identified a homozygous novel pathogenic variant in FGG gene. In our review the main symptom, at diagnosis, was umbilical cord bleeding and the degree of clinical involvement varied from asymptomatic to severe. The FGA gene was the most affected and possible hot spots were observed. Variants considered as loss of function were the most frequent. The association of vascular abnormalities in a patient with congenital afibrinogenemia alerts for a closer follow-up of vascular issues in these patients.
Prevalence and Outcomes of Pediatric In-Hospital Cardiac Arrest Associated With Pulmonary Hypertension*
Authors: Morgan Ryan W. , Topjian Alexis A. , Wang Yan , Atkin Natalie J. , Kilbaugh Todd J. , McGowan Francis X. , Berg Robert A. , Mercer-Rosa Laura , Sutton Robert M. , Himebauch Adam S.
Published: November 2019

Objectives:

In adult in-hospital cardiac arrest, pulmonary hypertension is associated with worse outcomes, but pulmonary hypertension–associated in-hospital cardiac arrest has not been well studied in children. The objective of this study was to determine the prevalence of pulmonary hypertension among children with in-hospital cardiac arrest and its impact on outcomes.

Design:

Retrospective single-center cohort study.

Setting:

PICU of a quaternary care, academic children’s hospital.

Patients:

Children (<18 yr old) receiving greater than or equal to 1 minute of cardiopulmonary resuscitation (cardiopulmonary resuscitation) for an index in-hospital cardiac arrest with an echocardiogram in the 48 hours preceding in-hospital cardiac arrest, excluding those with cyanotic congenital heart disease.

Interventions:

None.

Measurements and Main Results:

Of 284 in-hospital cardiac arrest subjects, 57 (20%) had evaluable echocardiograms, which were analyzed by a cardiologist blinded to patient characteristics. Pulmonary hypertension was present in 20 of 57 (35%); nine of 20 (45%) had no prior pulmonary hypertension history. Children with pulmonary hypertension had worse right ventricular systolic function, measured by fractional area change (p = 0.005) and right ventricular global longitudinal strain (p = 0.046); more right ventricular dilation (p = 0.010); and better left ventricular systolic function (p = 0.001). Children with pulmonary hypertension were more likely to have abnormal baseline functional status and a history of chronic lung disease or acyanotic congenital heart disease and less likely to have sepsis or acute kidney injury. Children with pulmonary hypertension were more likely to have an initial rhythm of pulseless electrical activity or asystole and were more frequently treated with inhaled nitric oxide (80% vs 32%; p < 0.001) at the time of cardiopulmonary resuscitation. On multivariable analysis, pulmonary hypertension was not associated with event survival (14/20 [70%] vs 24/37 [65%]; adjusted odds ratio, 1.30 [CI95, 0.25–6.69]; p = 0.77) or survival to discharge (8/20 [40%] vs 10/37 [27%]; adjusted odds ratio, 1.17 [CI95, 0.22–6.44]; p = 0.85).

Conclusions:

Pulmonary hypertension physiology preceding pediatric in-hospital cardiac arrest may be more common than previously described. Among this cohort with a high frequency of inhaled nitric oxide treatment during cardiopulmonary resuscitation, pulmonary hypertension was not associated with survival outcomes.