bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of a registry database for esophageal cancer from high-volume centers in China
Authors: Mao Y-S , Gao S-G , Wang Q , Shi X-T , Li Y , Gao W-J , Guan F-S , Li X F , Han Y-T , Liu Y-Y , Liu J-F , Zhang K , Liu S-Y , Fu X-N , Fang W-T , Chen L-Q , Wu Q-C , Xiao G-M , Chen K-N , Jiao G-G , Luo J-H , Mao W-M , Rong T-H , Fu J-H , Tang L-J , Chen C , Xu S-D , Guo S-P , Yu Z-T , Hu J , Hu Z-D , Sihoe A , Yang Y-K , Ding N-N , Yang D , Gao Y-B , He J
Published: December 2019

Esophageal cancer has a high incidence among malignancies in China, but a comprehensive picture of the status of its surgical management in China has hitherto not been available. A nationwide database has recently been established to address this issue. Method: A National Database was setup through a network platform, and data was collected from 70 high-volume centers (>100 esophagectomies/per year) across China. Data was entered between January 2009 and December 2014, and was analyzed in June 2015 after a minimal follow-up of 6 months for all patients. 8181 patients with complete data who received surgery for primary esophageal cancer on the Database were included in the analysis. Result: In this series, there were 6052 males and 2129 females, with a mean age of 60.5 years (range: 22–90 years). The pathology in 95.5% of patients was squamous cell carcinoma. The pathological stage distribution was 1.2% in stage 0, 2.5% in Ia, 11.5% in Ib, 14.8% in IIa, 36.1% in IIb, 19.3% in IIIa, 8.3% in IIIb, 6.2% in IIIc. 1800 patients (22.0%) with locally advanced disease received preoperative neoadjuvant therapy and 3592 patients (43.9%) underwent postoperative adjuvant chemotherapy and/or radiotherapy. The esophagectomies were performed through left thoracotomy approach in 5870 cases (72.6%), through right chest approach in 2215 cases (27.4%) including right thoracotomy (21.3%) and VATS (6.1%). The 30-day postoperative mortality rate was 0.6% (43 patients), and the overall postoperative complication rate was 11.6% (951 patients). The 1-, 3-, and 5-year overall survival rates were 82.6%, 61.6%, and 52.9%, respectively. Conclusion: This National Registry Database from high-volume centers provides a comprehensive picture of surgical management for esophageal cancer in China for the first time. Squamous cell carcinoma predominates, but there is heterogeneity with respect to the surgical approach and perioperative oncologic management. Overall, surgical mortality and morbidity rates are low, and good survival rates have been achieved due to improvement of surgical treatment technology in recent years.
Riboflavin Supplementation in Patients with Crohn’s Disease [the RISE-UP study]
Authors: von Martels Julius Z H , Bourgonje Arno R , Klaassen Marjolein A Y , Alkhalifah Hassan A A , Sadaghian Sadabad Mehdi , Vich Vila Arnau , Gacesa Ranko , Gabriëls Ruben Y , Steinert Robert E , Jansen Bernadien H , Bulthuis Marian L C , van Dullemen Hendrik M , Visschedijk Marijn C , Festen Eleonora A M , Weersma Rinse K , de Vos Paul , van Goor Harry , Faber Klaas Nico , Harmsen Hermie J M , Dijkstra Gerard
Published: December 2019

Background and Aims

Crohn’s disease [CD] is characterised by chronic intestinal inflammation and dysbiosis in the gut. Riboflavin [vitamin B2] has anti-inflammatory, antioxidant and microbiome-modulatory properties. Here, we analysed the effect of riboflavin on oxidative stress, markers of inflammation, clinical symptoms, and faecal microbiome in patients with CD.

Methods

In this prospective clinical intervention study, patients received 100 mg riboflavin [DSM, Nutritional Products Ltd] daily for 3 weeks. Clinical disease activity [Harvey-Bradshaw Index: HBI], serum biomarkers of inflammation and redox status [plasma free thiols], and faecal microbiome taxonomical composition and functionality [fluorescent in situ hybridisation: FISH; and metagenomic shotgun sequencing: MGS], were analysed before and after riboflavin intervention.

Results

In total, 70 patients with CD with varying disease activity were included. Riboflavin supplementation significantly decreased serum levels of inflammatory markers. In patients with low faecal calprotectin [FC] levels, IL-2 decreased, and in patients with high FC levels, C-reactive protein [CRP] was reduced and free thiols significantly increased after supplementation. Moreover, HBI was significantly decreased by riboflavin supplementation. Riboflavin supplementation led to decreased Enterobacteriaceae in patients with low FC levels as determined by FISH; however, MGS analysis showed no effects on diversity, taxonomy, or metabolic pathways of the faecal microbiome.

Conclusions

Three weeks of riboflavin supplementation resulted in a reduction in systemic oxidative stress, mixed anti-inflammatory effects, and a reduction in clinical symptoms [HBI]. FISH analysis showed decreased Enterobacteriaceae in patients with CD with low FC levels, though this was not observed in MGS analysis. Our data demonstrate that riboflavin supplementation has a number of anti-inflammatory and anti-oxidant effects in CD.
Percutaneous closure of an iatrogenic aorto-right atrial fistula of the sinus of Valsalva through total arm approach: a case report
Authors: Sood Nitin , Ehrlich Peter , Meerbach Dorothee , Kindermann Michael
Published: December 2019

Background 

Creation of an iatrogenic aorto-right atrial fistula is a rare but clinically relevant complication of cardiac surgery. Transfemoral percutaneous closure is an attractive alternative to surgical repair, but there are no reports about transcatheter repair using a complete arm access.

Case summary 

We present the case of a 44-year-old woman with heart failure (NewYork Heart Association Class III) due to a longstanding iatrogenic fistula from the non-coronary aortic cusp to the right atrium (RA) with aorta to RA shunting and severe tricuspid regurgitation (TR) caused by mitral valve replacement 15 years ago. The patient was successfully treated by percutaneous closure with an Amplatzer Vascular Plug II using complete brachial access. Following the procedure right heart chambers and TR decreased and symptoms resolved.

Discussion 

To the best of our knowledge this is the first report of percutaneous repair of an aorto-right atrial fistula using total arm accesses (radial artery and basilic vein). In appropriately selected patients, this approach is an attractive alternative to femoral access.
Amygdala-Based Altered miRNome and Epigenetic Contribution of miR-128-3p in Conferring Susceptibility to Depression-Like Behavior via Wnt Signaling
Authors: Roy Bhaskar , Dunbar Michael , Agrawal Juhee , Allen Lauren , Dwivedi Yogesh
Published: December 2019

Background

Recent studies suggest that microRNAs (miRNAs) can participate in depression pathogenesis by altering a host of genes that are critical in corticolimbic functioning. The present study focuses on examining whether alterations in the miRNA network in the amygdala are associated with susceptibility or resiliency to develop depression-like behavior in rats.

Methods

Amygdala-specific altered miRNA transcriptomics were determined in a rat depression model following next-generation sequencing method. Target prediction analyses (cis- and trans) and qPCR-based assays were performed to decipher the functional role of altered miRNAs. miRNA-specific target interaction was determined using in vitro transfection assay in neuroblastoma cell line. miRNA-specific findings from the rat in vivo model were further replicated in postmortem amygdala of major depressive disorder (MDD) subjects.

Results

Changes in miRNome identified 17 significantly upregulated and 8 significantly downregulated miRNAs in amygdala of learned helpless (LH) compared with nonlearned helpless rats. Prediction analysis showed that the majority of the upregulated miRNAs had target genes enriched for the Wnt signaling pathway. Among altered miRNAs, upregulated miR-128-3p was identified as a top hit based on statistical significance and magnitude of change in LH rats. Target validation showed significant downregulation of Wnt signaling genes in amygdala of LH rats. A discernable increase in expression of amygdalar miR-128-3p along with significant downregulation of key target genes from Wnt signaling (WNT5B, DVL, and LEF1) was noted in MDD subjects. Overexpression of miR-128-3p in a cellular model lead to a marked decrease in the expression of Dvl1 and Lef1 genes, confirming them as validated targets of miR-128-3p. Additional evidence suggested that the amygdala-specific diminished expression of transcriptional repressor Snai1 could be potentially linked to induced miR-128-2 expression in LH rats. Furthermore, an amygdala-specific posttranscriptional switching mechanism could be active between miR-128-3p and RNA binding protein Arpp21 to gain control over their target genes such as Lef1.

Conclusion

Our study suggests that in amygdala a specific set of miRNAs may play an important role in depression susceptibility, which could potentially be mediated through Wnt signaling.
Do Improving Conditions Harden Partisan Preferences? Lived Experiences, Imagined Communities, and Polarized Evaluations
Authors: Suk Jiyoun , Shah Dhavan V , Wells Chris , Wagner Michael W , Friedland Lewis A , Cramer Katherine J , Hughes Ceri , Franklin Charles
Published: December 2019

Despite growing attention to an increasing partisan divide and populist voting, little attention has been directed at how social contexts might encourage greater or lesser political polarization. We address this gap by studying how county-level conditions—economic resilience, population change, and community health—intersect with individuals’ political orientations and communication patterns to shape partisan evaluations. Our context is Wisconsin around the 2012 election, with our focus on two prominent political figures: Governor Scott Walker and President Barack Obama. Multilevel modeling reveals that partisans living in counties with more affluent, less precarious conditions during 2009–2012 exhibited more polarized partisan attitudes toward Walker and Obama. Our analysis also finds a significant role for interpersonal communication and digital media in shaping polarized attitudes.
It Depends on Who’s Asking: Interviewer Gender Effects on Credibility Ratings of Male and Female Journalists in Six Arab Countries
Authors: Martin Justin D
Published: December 2019

This study examined interviewer gender effects on attitudes toward male and female journalists in a survey experiment in six Arab countries. Respondents (N = 5,040) in Jordan, Lebanon, Qatar, Saudi Arabia, Tunisia, and UAE were read a scenario, by a male or female interviewer, of either a male or female journalist covering a political scandal, and were then asked about the journalist’s perceived credibility. Interviewer gender affected ratings of journalist conscientiousness in four of six countries (positively in Tunisia and UAE, and negatively in Jordan and Lebanon), and negatively affected knowledgeability ratings in Lebanon. Implications for research on media credibility, gender bias, and survey research are discussed.
Lack of synergistic nephrotoxicity between vancomycin and piperacillin/tazobactam in a rat model and a confirmatory cellular model
Authors: Pais Gwendolyn M , Liu Jiajun , Avedissian Sean N , Hiner Danielle , Xanthos Theodoros , Chalkias Athanasios , d’Aloja Ernesto , Locci Emanuela , Gilchrist Annette , Prozialeck Walter C , Rhodes Nathaniel J , Lodise Thomas P , Fitzgerald Julie C , Downes Kevin J , Zuppa Athena F , Scheetz Marc H
Published: December 2019

Background

Vancomycin and piperacillin/tazobactam are reported in clinical studies to increase acute kidney injury (AKI). However, no clinical study has demonstrated synergistic toxicity, only that serum creatinine increases.

Objectives

To clarify the potential for synergistic toxicity between vancomycin, piperacillin/tazobactam and vancomycin + piperacillin/tazobactam treatments by quantifying kidney injury in a translational rat model of AKI and using cell studies.

Methods

(i) Male Sprague–Dawley rats (n = 32) received saline, vancomycin 150 mg/kg/day intravenously, piperacillin/tazobactam 1400 mg/kg/day intraperitoneally or vancomycin + piperacillin/tazobactam for 3 days. Urinary biomarkers and histopathology were analysed. (ii) Cellular injury was assessed in NRK-52E cells using alamarBlue®.

Results

Urinary output increased from Day −1 to Day 1 with vancomycin but only after Day 2 for vancomycin + piperacillin/tazobactam-treated rats. Plasma creatinine was elevated from baseline with vancomycin by Day 2 and only by Day 4 for vancomycin + piperacillin/tazobactam. Urinary KIM-1 and clusterin were increased with vancomycin from Day 1 versus controls (P < 0.001) and only on Day 3 with vancomycin + piperacillin/tazobactam (P < 0.001, KIM-1; P < 0.05, clusterin). The histopathology injury score was elevated only in the vancomycin group when compared with piperacillin/tazobactam as a control (P = 0.04) and generally not so with vancomycin + piperacillin/tazobactam. In NRK-52E cells, vancomycin induced cell death with high doses (IC50 48.76 mg/mL) but piperacillin/tazobactam did not, and vancomycin + piperacillin/tazobactam was similar to vancomycin.

Conclusions

All groups treated with vancomycin demonstrated AKI; however, vancomycin + piperacillin/tazobactam was not worse than vancomycin. Histopathology suggested that piperacillin/tazobactam did not worsen vancomycin-induced AKI and may even be protective.
Variation in care of patients with elderly-onset inflammatory bowel disease in Ontario, Canada: A population-based cohort study
Authors: Kuenzig M Ellen , Stukel Therese A , Kaplan Gilaad G , Murthy Sanjay K , Nguyen Geoffrey C , Talarico Robert , Benchimol Eric I
Published: December 2019

Background

Variation in health care, when not based on patient preference, may result in poorer care. We determined whether variation in health services utilization, gastroenterologist care and outcomes existed among patients with elderly-onset inflammatory bowel disease (IBD).

Methods

Patients with IBD (diagnosed ≥65 years) were identified from population-based health administrative data from Ontario, Canada (1999 to 2014). We assessed variation across multispecialty physician networks in gastroenterologist care and outcomes using multilevel logistic regression. Median odds ratios (MOR) described variation. We evaluated the association between gastroenterologist supply, specialist care and outcomes.

Results

In 4806 patients, there was significant variation in having ever seen a gastroenterologist (MOR 3.35, P < 0.0001), having a gastroenterologist as the primary IBD care provider (MOR 4.16, P < 0.0001), 5-year colectomy risk in ulcerative colitis (MOR 1.38, P = 0.01), immunomodulator use (MOR 1.47, P = 0.001), and corticosteroid use (MOR 1.26, P = 0.006). No variation in emergency department visits, hospitalizations or intestinal resection (Crohn’s) was noted. Patients in networks with fewer gastroenterologists were less likely to see a gastroenterologist (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.15 to 0.56), have a gastroenterologist as their primary care provider (OR 0.27, 95% CI 0.12 to 0.59), be hospitalized within 5 years (OR 0.82, 95% CI 0.69 to 0.98), and be prescribed biologics within 1 year (OR 0.50, 95% CI 0.28 to 0.89).

Conclusions

Utilization of gastroenterology care in patients with elderly-onset IBD varies greatly. Patients treated by gastroenterologists and in networks with more gastroenterologists have better outcomes. There is a need to ensure all individuals with IBD have equal access to and utilization of specialist care to ensure the best possible outcomes.
Hybrid repair of isolated internal iliac artery aneurysm
Authors: Kawatani Yohei , Oguri Atsushi
Published: December 2019

The best operation method for an isolated internal iliac artery aneurysm remains controversial. We report on a repair of an isolated internal iliac artery aneurysm. A 78-year-old man was referred to our facility for treatment of a left isolated internal iliac artery aneurysm. At first, we embolized the arteries distal to the aneurysm using coils and vascular plugs. Two weeks later, we performed open surgery. We resected the aneurysm wall through a transperitoneal approach only with proximal blood flow control and without surgical exposure and clamping of the arteries distal to the aneurysm. The blood flow of the internal iliac artery distal to the aneurysm had completely ceased after embolization in the first stage, which enabled us to avoid further pelvic dissection and potential bleeding. At the 6-month follow up, the patient was well and without complaints.
Molecular structure of a U•A-U-rich RNA triple helix with 11 consecutive base triples
Authors: Ruszkowska Agnieszka , Ruszkowski Milosz , Hulewicz Jacob P , Dauter Zbigniew , Brown Jessica A
Published: December 2019

Three-dimensional structures have been solved for several naturally occurring RNA triple helices, although all are limited to six or fewer consecutive base triples, hindering accurate estimation of global and local structural parameters. We present an X-ray crystal structure of a right-handed, U•A-U-rich RNA triple helix with 11 continuous base triples. Due to helical unwinding, the RNA triple helix spans an average of 12 base triples per turn. The double helix portion of the RNA triple helix is more similar to both the helical and base step structural parameters of A′-RNA rather than A-RNA. Its most striking features are its wide and deep major groove, a smaller inclination angle and all three strands favoring a C3′-endo sugar pucker. Despite the presence of a third strand, the diameter of an RNA triple helix remains nearly identical to those of DNA and RNA double helices. Contrary to our previous modeling predictions, this structure demonstrates that an RNA triple helix is not limited in length to six consecutive base triples and that longer RNA triple helices may exist in nature. Our structure provides a starting point to establish structural parameters of the so-called ‘ideal’ RNA triple helix, analogous to A-RNA and B-DNA double helices.
Characterization of Oil Palm Acyl-CoA-Binding Proteins and Correlation of Their Gene Expression with Oil Synthesis
Authors: Amiruddin Nadzirah , Chan Pek-Lan , Azizi Norazah , Morris Priscilla Elizabeth , Chan Kuang-Lim , Ong Pei Wen , Rosli Rozana , Masura Subhi Siti , Murphy Denis J , Sambanthamurthi Ravigadevi , Haslam Richard P , Chye Mee-Len , Harwood John L , Low Eng-Ti Leslie
Published: December 2019

Acyl-CoA-binding proteins (ACBPs) are involved in binding and trafficking acyl-CoA esters in eukaryotic cells. ACBPs contain a well-conserved acyl-CoA-binding domain. Their various functions have been characterized in the model plant Arabidopsis and, to a lesser extent, in rice. In this study, genome-wide detection and expression analysis of ACBPs were performed on Elaeis guineensis (oil palm), the most important oil crop in the world. Seven E. guineensis ACBPs were identified and classified into four groups according to their deduced amino acid domain organization. Phylogenetic analysis showed conservation of this family with other higher plants. All seven EgACBPs were expressed in most tissues while their differential expression suggests various functions in specific tissues. For example, EgACBP3 had high expression in inflorescences and stalks while EgACBP1 showed strong expression in leaves. Because of the importance of E. guineensis as an oil crop, expression of EgACBPs was specifically examined during fruit development. EgACBP3 showed high expression throughout mesocarp development, while EgACBP1 had enhanced expression during rapid oil synthesis. In endosperm, both EgACBP1 and EgACBP3 exhibited increased expression during seed development. These results provide important information for further investigations on the biological functions of EgACBPs in various tissues and, in particular, their roles in oil synthesis.
Examining the optimal timing for closed-loop auditory stimulation of slow-wave sleep in young and older adults
Authors: Navarrete Miguel , Schneider Jules , Ngo Hong-Viet V , Valderrama Mario , Casson Alexander J , Lewis Penelope A
Published: December 2019

Study Objectives

Closed-loop auditory stimulation (CLAS) is a method for enhancing slow oscillations (SOs) through the presentation of auditory clicks during sleep. CLAS boosts SOs amplitude and sleep spindle power, but the optimal timing for click delivery remains unclear. Here, we determine the optimal time to present auditory clicks to maximize the enhancement of SO amplitude and spindle likelihood.

Methods

We examined the main factors predicting SO amplitude and sleep spindles in a dataset of 21 young and 17 older subjects. The participants received CLAS during slow-wave-sleep in two experimental conditions: sham and auditory stimulation. Post-stimulus SOs and spindles were evaluated according to the click phase on the SOs and compared between and within conditions.

Results

We revealed that auditory clicks applied anywhere on the positive portion of the SO increased SO amplitudes and spindle likelihood, although the interval of opportunity was shorter in the older group. For both groups, analyses showed that the optimal timing for click delivery is close to the SO peak phase. Click phase on the SO wave was the main factor determining the impact of auditory stimulation on spindle likelihood for young subjects, whereas for older participants, the temporal lag since the last spindle was a better predictor of spindle likelihood.

Conclusions

Our data suggest that CLAS can more effectively boost SOs during specific phase windows, and these differ between young and older participants. It is possible that this is due to the fluctuation of sensory inputs modulated by the thalamocortical networks during the SO.
Hyperferritinemia in Critically Ill Patients*
Authors: Lachmann Gunnar , Knaak Cornelia , Vorderwülbecke Gerald , La Rosée Paul , Balzer Felix , Schenk Thomas , Schuster Friederike S. , Nyvlt Peter , Janka Gritta , Brunkhorst Frank M. , Keh Didier , Spies Claudia
Published: December 2019

Objective:

Hyperferritinemia is frequently seen in critically ill patients. A rather rare though life-threatening condition related to severely elevated ferritin is hemophagocytic lymphohistiocytosis. We analyze ferritin levels to differentiate hemophagocytic lymphohistiocytosis from other causes of hyperferritinemia in a mixed cohort of critically ill patients.

Design:

Retrospective observational study.

Setting:

Adult surgical, anesthesiologic, and medical ICUs of a university hospital.

Patients:

Critical care patients (≥ 18 yr old) admitted to any of the adult ICUs at Charité – Universitätsmedizin Berlin between January 2006 and August 2018 with at least one ferritin value and hyperferritinemia (≥ 500 µg/L).

Interventions:

None.

Measurements and Main Results:

Patients were categorized into hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other diagnoses. These were further categorized into 17 subgroups. Hemophagocytic lymphohistiocytosis diagnosis was based on Hemophagocytic Lymphohistiocytosis-2004 criteria and the HScore. Of 2,623 patients with hyperferritinemia, 40 were considered to have hemophagocytic lymphohistiocytosis (1.52%). Maximum ferritin levels were highest in hemophagocytic lymphohistiocytosis patients compared with all other disease groups (each p < 0.001). Sepsis and septic shock patients had higher maximum ferritin levels than patients with other diagnoses (each p < 0.001). A maximum ferritin value of 9,083 µg/L was at 92.5% sensitivity and 91.9% specificity for hemophagocytic lymphohistiocytosis (area under the curve, 0.963; 95% CI, 0.949–0.978). Of all subgroups with other diagnoses, maximum ferritin levels were highest in patients with varicella-zoster virus, hepatitis, or malaria (median, 1,935, 1,928, and 1,587 µg/L, respectively). Maximum ferritin levels were associated with increased in-hospital mortality (odds ratio, 1.518 per log µg/L [95% CI, 1.384–1.665 per log µg/L]; p < 0.001).

Conclusions:

This is the largest study of patients with ferritin available in a mixed ICU cohort. Ferritin levels in patients with hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other conditions were distinctly different, with the highest ferritin levels observed in hemophagocytic lymphohistiocytosis patients. Maximum ferritin of 9,083 µg/L showed high sensitivity and specificity and, therefore, may contribute to improved diagnosis of hemophagocytic lymphohistiocytosis in ICU. The inclusion of ferritin into the sepsis laboratory panel is warranted.
Monitoring diaphragm function in the ICU
Authors: Dres Martin , Demoule Alexandre
Published: December 2019

Purpose of review

To review the clinical problem of diaphragm function in critically ill patients and describes recent advances in bedside monitoring of diaphragm function.

Recent findings

Diaphragm weakness, a consequence of diaphragm dysfunction and atrophy, is common in the ICU and associated with serious clinical consequences. The use of ultrasound to assess diaphragm structure (thickness, thickening) and mobility (caudal displacement) appears to be feasible and reproducible, but no large-scale ‘real-life’ study is available. Diaphragm ultrasound can also be used to evaluate diaphragm muscle stiffness by means of shear-wave elastography and strain by means of speckle tracking, both of which are correlated with diaphragm function in healthy. Electrical activity of the diaphragm is correlated with diaphragm function during brief airway occlusion, but the repeatability of these measurements exhibits high within-subject variability.

Mechanical ventilation is involved in the pathogenesis of diaphragm dysfunction, which is associated with severe adverse events. Although ultrasound and diaphragm electrical activity could facilitate monitoring of diaphragm function to deliver diaphragm-protective ventilation, no guidelines concerning the use of these modalities have yet been published. The weaning process, assessment of patient–ventilator synchrony and evaluation of diaphragm function may be the most clinically relevant indications for these techniques.
Unusual Late-onset Enteropathy in a Patient With Lipopolysaccharide-responsive Beige-like Anchor Protein Deficiency
Authors: Maggiore Rosario , Grossi Alice , Fioredda Francesca , Palmisani Elena , Terranova Paola , Cappelli Enrico , Lanza Tiziana , Pierri Filomena , Guardo Daniela , Calvillo Michaela , Micalizzi Concetta , Beccaria Andrea , Coccia Maria C. , Arrigo Serena , Dufour Carlo , Ceccherini Isabella , Miano Maurizio
Published: December 2019

In recent years, monogenic causes of immune dysregulation syndromes, with variable phenotypes, have been documented. Mutations in the lipopolysaccharide-responsive beige-like anchor (LRBA) protein are associated with common variable immunodeficiency, autoimmunity, chronic enteropathy, and immune dysregulation disorders. The LRBA protein prevents degradation of cytotoxic T-lymphocyte antigen 4 (CTLA4) protein, thus inhibiting immune responses. Both LRBA and CTLA4 deficiencies usually present with immune dysregulation, mostly characterized by autoimmunity and lymphoproliferation. In this report, we describe a patient with an atypical clinical onset of LRBA deficiency and the patient’s response to abatacept, a fusion protein-drug that mimics the action of CTLA4.
Impact of Insurance Payer on Type of Breast Reconstruction Performed
Authors: Chouairi Fouad , Mets Elbert J. , Gabrick Kyle S. , Dinis Jacob , Avraham Tomer , Alperovich Michael
Published: December 2019

Background:

The impact of insurance and socioeconomic status on breast reconstruction modalities when access to care is controlled is unknown.

Methods:

Records for patients who underwent breast reconstruction at an academic medical center between 2013 and 2017 were reviewed and analyzed using chi-square analysis and logistic regression.

Results:

One thousand six hundred eighty-three breast reconstructions were analyzed. The commercially insured were more likely to undergo microvascular autologous breast reconstruction (44.4 percent versus 31.3 percent; p < 0.001), with an odds ratio of 2.22, whereas patients with Medicare and Medicaid were significantly more likely to receive tissue expander/implant breast reconstruction, with an odds ratio of 1.42 (41.7 percent versus 47.7 percent; p = 0.013). Comparing all patients with microvascular reconstruction, the commercially insured were more likely to receive a perforator flap (79.7 percent versus 55.3 percent versus 43.9 percent), with an odds ratio of 4.23 (p < 0.001). When stratifying patients by median household income, those in the highest income quartile were most likely to receive a perforator flap (82.1 percent) (p < 0.001), whereas those in the lowest income quartile were most likely to receive a muscle-sparing transverse rectus abdominis myocutaneous flap (36.4 percent) (p < 0.001).

Conclusions:

Patients at the same academic medical center had significantly different breast reconstruction modalities when stratified by insurance and household income. Despite similar access to care, differences in insurance types may favor higher rates of perforator flap breast reconstruction among the commercially insured.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Bilateral End-Organ Endophthalmitis in Setting of Serratia marcescens Urosepsis on 18F-FDG PET/CT
Authors: Makusha Lovemore P. , Young Colin R. , Agarwal Daniel R. , Pucar Darko
Published: December 2019

Endogenous endophthalmitis is an uncommon infection of the internal tissues of the eye resulting from a bloodborne infection. We present the case of an 89-year-old man with Serratia marcescens urosepsis with multifocal end-organ infection on 18F-FDG PET/CT including aortitis, splenic abscess, septic arthritis, thoracolumbar discitis-osteomyelitis, and culture-confirmed bilateral endogenous endophthalmitis. Endophthalmitis-related intraconal ocular space uptake was clearly distinguishable from normal conal space extraocular muscle activity. Although sepsis responded to treatment, endophthalmitis led to complete vision loss. This case report presents PET/CT description of a rare and difficult-to-treat Serratia marcescens endogenous endophthalmitis, which usually has a poor visual outcome.
Outcomes of Patients Treated With Upfront Cholecystostomy for Severe Acute Cholecystitis
Authors: De Geus Thea , Moriarty Heather K. , Waters Peadar S. , O’Reilly Michael K. , Lawler Leo , Geoghegan Tony , Conneely John C. , McEntee Gerry , Farrelly Cormac
Published: December 2019

Introduction:

Percutaneous cholecystostomy tube (PCT) placement is a treatment method for acute cholecystitis, both in adult patients unsuitable for surgery and those failing to improve with conservative management. The purpose of this study was to assess the outcomes of patients undergoing cholecystostomy.

Materials and Methods:

A review of consecutive patients who underwent PCT insertion over a 10-year period was performed. Outcomes assessed included cholecystostomy dwell time, tubogram requirement, cholecystostomy reinsertion, cholecystectomy, bile leaks, and mortality.

Results:

One hundred eight patients (77 male individuals, 31 female individuals) were included. The mean age was 70 years (range: 29 to 93 y). A total of 89 transhepatic and 19 transperitoneal PCTs were inserted. Fifty-nine patients (55%) had a subsequent tubogram to assess cystic duct patency or catheter position. Mean catheter dwell time was 17 days (range: 1 to 154 d). Eleven (10%) required PCT reinsertion. Time to reinsertion ranged from 2 to 163 days (mean=38 d). Fifty-three patients (50%) had no further biliary intervention after removal of the cholecystostomy catheter. One patient required subsequent drainage of a hepatic abscess, and another developed a biloma. Thirty-two patients (30%) underwent cholecystectomy (66% laparoscopic, 34% open). Thirty-day mortality after PCT insertion was 8.3%. Twenty patients (19%) died of non–cholecystostomy-related illness during the 10-year follow-up period.

Conclusions:

Cholecystostomy is an important treatment method of acute cholecystitis as a bridge to cholecystectomy or as an alternative definitive treatment option in those unsuitable for surgery. A tubogram is not always necessary before tube removal. Cholecystostomy tubes can be removed safely with little risk of bile leak if patients are clinically well, and clean-appearing bile is draining.
Injury characteristics of the Pulse Nightclub shooting: Lessons for mass casualty incident preparation
Authors: Smith Chadwick P. , Cheatham Michael L. , Safcsak Karen , Emrani Heidi , Ibrahim Joseph A. , Gregg Michael , Eubanks William S. , Lube Matthew W. , Havron William S. , Levy Marc S.
Published: December 2019

BACKGROUND

On the morning of June 12, 2016, an armed assailant entered the Pulse Nightclub in Orlando, Florida, and initiated an assault that killed 49 people and injured 53. The regional Level I trauma center and two community hospitals responded to this mass casualty incident. A detailed analysis was performed to guide hospitals who strive to prepare for future similar events.

METHODS

A retrospective review of all victim charts and/or autopsy reports was performed to identify victim presentation patterns, injuries sustained, and surgical resources required. Patients were stratified into three groups: survivors who received care at the regional Level I trauma center, survivors who received care at one of two local community hospitals, and decedents.

RESULTS

Of the 102 victims, 40 died at the scene and 9 died upon arrival to the Level I trauma center. The remaining 53 victims received definitive medical care and survived. Twenty-nine victims were admitted to the trauma center and five victims to a community hospital. The remaining 19 victims were treated and discharged that day. Decedents sustained significantly more bullet impacts than survivors (4 ± 3 vs. 2 ± 1; p = 0.008) and body regions injured (3 ± 1 vs. 2 ± 1; p = 0.0002). Gunshots to the head, chest, and abdominal body regions were significantly more common among decedents than survivors (p < 0.0001). Eighty-two percent of admitted patients required surgery in the first 24 hours. Essential resources in the first 24 hours included trauma surgeons, emergency room physicians, orthopedic/hand surgeons, anesthesiologists, vascular surgeons, interventional radiologists, intensivists, and hospitalists.

CONCLUSION

Mass shooting events are associated with high mortality. Survivors commonly sustain multiple, life-threatening ballistic injuries requiring emergent surgery and extensive hospital resources. Given the increasing frequency of mass shootings, all hospitals must have a coordinated plan to respond to a mass casualty event.

LEVEL OF EVIDENCE

Epidemiological Study, level V.
Staphylococcus aureusstaphyloxanthin expression is not controlled by Hfq
Authors: Liu Wenfeng , Boudry Pierre , Bohn Chantal , Bouloc Philippe
Published: December 2019

Objective

The golden color ofStaphylococcus aureusis due to the synthesis of carotenoid pigments. In Gram-negative bacteria, Hfq is a global posttranscriptional regulator, but its function inS. aureusremains obscure. The absence of Hfq inS. aureuswas reported to correlate with production of carotenoid pigment leading to the conclusion that Hfq was a negative regulator of the yellow color. However, we reported the construction ofhfqmutants in severalS. aureusstrains and never noticed any color change; we therefore revisited the question of Hfq implication inS. aureuspigmentation.

Results

The absence or accumulation of Hfq does not affectS. aureuspigmentation.
Rethinking causality and data complexity in brain lesion-behaviour inference and its implications for lesion-behaviour modelling
Authors: Sperber Christoph
Published: December 2019

Modelling behavioural deficits based on structural lesion imaging is a popular approach to map functions in the human brain, and efforts to translationally apply lesion-behaviour modelling to predict post-stroke outcomes are on the rise. The high-dimensional complexity of lesion data, however, evokes challenges in both lesion behaviour mapping and post stroke outcome prediction. This paper aims to deepen the understanding of this complexity by reframing it from the perspective of causal and non-causal dependencies in the data, and by discussing what this complexity implies for different data modelling approaches. By means of theoretical discussion and empirical examination, several common strategies and views are challenged, and future research perspectives are outlined. A main conclusion is that lesion-behaviour inference is subject to a lesion-anatomical bias that cannot be overcome by using multivariate models or any other algorithm that is blind to causality behind relations in the data. This affects the validity of lesion behaviour mapping and might even wrongfully identify paradoxical effects of lesion-induced functional facilitation – but, as this paper argues, only to a minor degree. Thus, multivariate lesion-brain inference appears to be a valuable tool to deepen our understanding of the human brain, but only because it takes into account the functional relation between brain areas. The perspective of causality and inter-variable dependence is further used to point out challenges in improving lesion behaviour models. Firstly, the dependencies in the data open up different possible strategies of data reduction, and considering those might improve post-stroke outcome prediction. Secondly, the role of non-topographical causal predictors of post stroke behaviour is discussed. The present article argues that, given these predictors, different strategies are required in the evaluation of model quality in lesion behaviour mapping and post stroke outcome prediction.
The Autism Biomarkers Consortium for Clinical Trials (ABC-CT): Scientific Context, Study Design, and Progress towards Biomarker Qualification
Authors: McPartland James C. , Bernier Raphael A. , Jeste Shafali S. , Dawson Geraldine , Nelson Charles A. , Chawarska Katarzyna , Earl Rachel , Faja Susan , Johnson Scott , Sikich Linmarie , Brandt Cynthia A. , Dziura James D. , Rozenblit Leon , Hellemann Gerhard , Levin April R. , Murias Michael , Naples Adam J. , Platt Michael L. , Sabatos-DeVito Maura , Shic Frederick , Senturk Damla , Sugar Catherine A. , Webb Sara J. ,   the Autism Biomarkers Consortium for Clinical Trials
Published: December 2019

Clinical research in neurodevelopmental disorders remains reliant upon clinician and caregiver measures. Limitations of these approaches indicate a need for objective, quantitative, and reliable biomarkers to advance clinical research. Extant research suggests the potential utility of multiple candidate biomarkers; however, effective application of these markers in trials requires additional understanding of replicability, individual differences, and intra-individual stability over time. The Autism Biomarkers Consortium for Clinical Trials (ABC-CT) is a multi-site study designed to investigate a battery of electrophysiological (EEG) and eye-tracking (ET) indices as candidate biomarkers for autism spectrum disorder (ASD). The study complements published biomarker research through: inclusion of large, deeply phenotyped cohorts of children with autism spectrum disorder (ASD) and typical development; a longitudinal design; a focus on well-evidenced candidate biomarkers harmonized with an independent sample; high levels of clinical, regulatory, technical, and statistical rigor; adoption of a governance structure incorporating diverse expertise in the ASD biomarker discovery and qualification process; prioritization of open science, including creation of a repository containing biomarker, clinical, and genetic data; and use of economical and scalable technologies that are applicable in developmental populations and those with special needs. The ABC-CT approach has yielded encouraging results, with one measure accepted into the FDA’s Biomarker Qualification Program to date. Through these advances, the ABC-CT and other biomarker studies in progress hold promise to deliver novel tools to improve clinical trials research in ASD.
Assessing the effectiveness of a pediatrician-led newborn parenting class on maternal newborn-care knowledge, confidence and anxiety: A nonrandomized controlled trial
Authors: Gozali Aileen , Gibson Sherika , Lipton Lianna R. , Pressman Aliza W. , Hammond Blair S. , Dumitriu Dani
Published: December 2019

Background

The postpartum hospital stay is a unique opportunity for clinicians to educate parents on the importance of promoting early child development. Pediatricians are well positioned to address both medical and developmental concerns during critical periods of development, yet very few parenting interventions are led by pediatricians.

Aims

To assess the impact of a novel one-hour long pediatrician-led Newborn Class on maternal knowledge, confidence, and anxiety.

Methods

We conducted a nonrandomized controlled trial to evaluate the effectiveness of the Newborn Class. First-time mothers who delivered a full-term singleton vaginally with no major complications and attended the class were recruited. Mothers who expressed a desire to attend the class but were discharged before a class was offered served as controls.

Outcome measures

Maternal self-perceived anxiety and confidence were measured using standardized scales (State-Trait Anxiety Inventory for Adults and Karitane Parenting Confidence Scale). Knowledge on new-born care was assessed using a novel scale.

Results

A total of 84 participants (intervention n=36, control n=48) were included in the study. Mothers who attended class showed significantly higher levels of knowledge compared to the control group as well as significantly higher parenting confidence levels. No change was observed in the overall level of anxiety.

Conclusions

A short pediatrician-led parenting intervention can be an effective tool in improving maternal confidence and newborn care knowledge. Given the importance of the newborn period in establishing healthy developmental trajectories, this cost- and time-effective intervention could be widely implemented to promote early strong mother-infant relationships that foster healthy development.
PRDM3 attenuates pancreatitis and pancreatic tumorigenesis by regulating inflammatory response
Authors: Ye Jie , Huang Anpei , Wang Haitao , Zhang Anni M.Y. , Huang Xiaojun , Lan Qingping , Sato Tomohiko , Goyama Susumu , Kurokawa Mineo , Deng Chuxia , Sander Maike , Schaeffer David F. , Li Wen , Kopp Janel L. , Xie Ruiyu
Published: December 2019

Pancreatic ductal adenocarcinoma (PDAC) is associated with metaplastic changes in the pancreas but the transcriptional program underlying these changes is incompletely understood. The zinc finger transcription factor, PRDM3, is lowly expressed in normal pancreatic acini and its expression increases during tumorigenesis. Although PRDM3 promotes proliferation and migration of PDAC cell lines, the role of PRDM3 during tumor initiation from pancreatic acinar cellsin vivois unclear. In this study, we showed that high levels of PRDM3 expression in human pancreas was associated with pancreatitis, and well-differentiated but not poorly differentiated carcinoma. We examined PRDM3 function in pancreatic acinar cells during tumor formation and pancreatitis by inactivatingPrdm3using a conditional allele (Ptf1aCreER;Prdm3flox/floxmice) in the context of oncogenic Kras expression and supraphysiological cerulein injections, respectively. InPrdm3-deficient mice, KrasG12D-driven preneoplastic lesions were more abundant and progressed to high-grade precancerous lesions more rapidly. This is consistent with our observations that low levels of PRDM3 in human PDAC was correlated significantly with poorer survival in patient. Moreover, loss ofPrdm3in acinar cells elevated exocrine injury, enhanced immune cell activation and infiltration, and greatly increased acinar-to-ductal cell reprogramming upon cerulein-induced pancreatitis. Whole transcriptome analyses ofPrdm3knockout acini revealed that pathways involved in inflammatory response and Hif-1 signaling were significantly upregulated inPrdm3-depleted acinar cells. Taken together, our results suggest that Prdm3 favors the maintenance of acinar cell homeostasis through modulation of their response to inflammation and oncogenic Kras activation, and thus plays a previously unexpected suppressive role during PDAC initiation.
Influence of socioeconomic factors on cancer incidence and stage of melanoma in China
Authors: Qian Leqi , Liu Jiaqi
Published: December 2019

Background

A high socioeconomic status (SES) was considered as an established risk factor for melanoma in western countries and areas, the same was not true in China. There have been few studies on SES of Chinese melanoma patients. The purpose of this study was to evaluate the association of SES in Chinese melanoma patients.

Methods

We performed a cross-sectional study using the data from Ministry of Human Resources and Social Security of the People’s Republic of China, and National Healthcare Security Administration. The clinical stage at diagnosis was categorized according to Guidelines of Chinese Society Oncology, Melanoma.

Results

We enrolled 122 patients with pathologic melanoma in Zhongshan Hospital, Fudan University between January 2013 to December 2017. 58 (48%) were male and 64 (52%) were female, the mean age was 59.23±9.91 years and median age was 60.5 years. Patients in 45-59 age group and 60-73 age group tend to have higher cancer incidence compared with other age groups. The acral lentiginous melanoma (48%) was the most common subtype. Patients with low education level (middle school and below) and low monthly household income (< 3000CNY) were associated with a greater risk of melanoma. Similar results were indicated for the patients who were unemployed. There were remarkable more patients who had medical insurance diagnosed with melanoma in this study. There was no significant difference on melanoma stage for patients with higher compared to lower education level (p=0.153). For monthly household income, the Fish’s exact test indicated no significant difference in melanoma stage with p=0.507. No staging difference was observed between unemployed patients and employed patients (p=0.687). Finally, statistically significant differences in melanoma staging were not indicated by a patient’s insurance status (p=0.537).

Conclusions

For patients enrolled in our study, disadvantaged SES did not substantially lead to an increasing risk of melanoma incidence, and the effect of socioeconomic factors seemed uninfluenced the stage of melanoma.