bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing of Intubation and In-Hospital Mortality in Patients With Coronavirus Disease 2019
Authors: Hyman Jaime B. , Leibner Evan S. , Tandon Pranai , Egorova Natalia N. , Bassily-Marcus Adel , Kohli-Seth Roopa , Arvind Varun , Chang Helena L. , Lin Hung-Mo , Levin Matthew A. 
Published: October 2020

Objectives:To examine whether increasing time between admission and intubation was associated with mortality in patients with coronavirus disease 2019 who underwent mechanical ventilation.Design:Retrospective cohort study of patients with severe acute respiratory syndrome coronavirus 2 infection who were admitted between January 30, 2020, and April 30, 2020, and underwent intubation and mechanical ventilation prior to May 1, 2020. Patients were followed up through August 15, 2020.Setting:Five hospitals within the Mount Sinai Health System in New York City, NY.Patients:Adult patients with severe acute respiratory syndrome coronavirus 2 infection who underwent intubation and mechanical ventilation.Interventions:Tracheal intubation and mechanical ventilation.Measurements and Main Results:The primary outcome was in-hospital mortality. A hospital-stratified time-varying Cox model was used to evaluate the effect of time from admission to intubation on in-hospital death. A total of 755 adult patients out of 5,843 admitted with confirmed severe acute respiratory syndrome coronavirus 2 infection underwent tracheal intubation and mechanical ventilation during the study period. The median age of patients was 65 years (interquartile range, 56–72 yr) and 64% were male. As of the time of follow-up, 121 patients (16%) who were intubated and mechanically ventilated had been discharged home, 512 (68%) had died, 113 (15%) had been discharged to a skilled nursing facility, and 9 (1%) remained in the hospital. The median time from admission to intubation was 2.3 days (interquartile range, 0.6–6.3 d). Each additional day between hospital admission and intubation was significantly associated with higher in-hospital death (adjusted hazard ratio, 1.03; 95% CI, 1.01–1.05).Conclusions:Among patients with coronavirus disease 2019 who were intubated and mechanically ventilated, intubation earlier in the course of hospital admission may be associated with improved survival.
Spectrum of Vascular Involvement in Coronavirus Disease 2019 Pneumonia—Findings on CT Perfusion
Authors: von der Thüsen Jan H. , Ghariq Elyas , Overbeek Maria J. , Leyten Eliane , Drijkoningen Tessa , Gietema Hester A. , Prokop Mathias , Quarles van Ufford Henriette M. E. 
Published: October 2020

Objectives:
There is accumulating evidence of a distinct coagulopathy in severe acute respiratory syndrome coronavirus 2 infection which is associated with poor prognosis in coronavirus disease 2019. Coagulation abnormalities in blood samples resemble systemic coagulopathies in other severe infections but demonstrate specific features such as a very high d-dimer. These clinical observations are consistent with histopathologic findings of locally disturbed pulmonary microvascular thrombosis and angiopathy in end-stage coronavirus disease 2019. However, exact underlying processes and the sequence of events are not fully understood.

Data Sources:
CT perfusion may provide insight in the dynamic aspect of the vascularity in pulmonary lesions in coronavirus disease 2019 infection as, in contrast to dual energy CT, a multiphase perfusion pattern is displayed.

Study Selection:
In six patients with coronavirus disease 2019 pneumonia, findings on additional CT perfusion series were correlated with known histopathologic vascular patterns upon pulmonary autopsy of patients who had died of coronavirus disease 2019.

Data Extraction:
In this case series, we were able to show perfusion changes on CT scans in typical pulmonary lesions illustrating diverse patterns.

Data Synthesis:
We demonstrated hyperperfusion in areas with ground glass and a severely decreased perfusion pattern in more consolidated areas often seen later in the course of disease. A combination was also observed, illustrating temporal heterogeneity.

Conclusions:
These findings provide new insights into the pathophysiology of coronavirus disease 2019 pneumonia and further understanding of the mechanisms that lead to respiratory failure in these patients.
131I-metaiodobenzylguanidine and peptide receptor radionuclide therapy in pheochromocytoma and paraganglioma
Authors: Jungels Christiane , Karfis Ioannis 
Published: October 2020

Purpose of review
Pheochromocytomas and paragangliomas are rare tumors arising, respectively, from the adrenal medulla and extra-adrenal sympathetic or parasympathetic paraganglia. The main therapeutic objectives in case of metastatic disease are the reduction of tumor burden and the control of symptoms resulting from excessive catecholamine secretion. Treatment choices constitute not only a wait and see attitude, locoregional approaches, chemotherapy regiments but also radiopharmaceutical agents, and they should be discussed in a specialized multidisciplinary board. This review will briefly discuss the radiopharmaceutical modalities in patients with pheochromocytomas and paragangliomas (131I-MIBG and PRRT).

Recent findings

131I-MIBG (Azedra) has received FDA approval for patients with iobenguane-scan-positive, unresectable, locally advanced or metastatic pheochromocytomas and paragangliomas who require systemic anticancer therapy, whereas peptide receptor radionuclide therapy using radiolabelled somatostatin analogues is currently performed in compassionate use, with very promising results. No prospective head-to-head comparison between the modalities has been conducted to date.

Summary
Promising results have been reported for both radiopharmaceutical agents, mostly in the setting of retrospective series. No prospective head-to-head comparison between the modalities is yet available.
Epigenetic in medullary thyroid cancer: the role of microRNA in tumorigenesis and prognosis
Authors: Manso Jacopo , Censi Simona , Mian Caterina 
Published: October 2020

Purpose of review
MicroRNAs emerged as pivotal regulators of cell differentiation, growth, and cell death, suggesting their implication in tumorigenesis and prognosis of cancer. In the last decades, knowledge about the alterations of microRNAs in medullary thyroid cancer (MTC) is increasing. In this review, we try to summarize the most relevant findings regarding microRNA dysregulation in MTC.

Recent findings
A literature analysis was performed in MEDLINE for studies published up to August 2020. Comprehensively, at least 27 different microRNAs have been investigated in MTC showing evidence for overexpression or underexpression in comparison with normal thyroid tissue samples, healthy blood controls, or primary tumor site or hereditary form of MTC. We highlight the evidence in favor of a possible use of microRNAs for diagnosis, prognosis and treatment in MTC and their role in MTC pathogenesis.

Summary
This review reveals the emerging complexity of the molecular genetic and epigenetic panorama in MTC. Further studies are needed to confirm and refine the findings on microRNA expression pattern in MTC. Thus, in the future, microRNA analysis could enter in clinical practice and may pave the way to new risk-stratification tools and novel therapeutic approaches for MTC.
Referral Trends in Two Pioneering Developmental-Behavioral Pediatric Centers in Turkey
Authors: Bingoler Pekcici Emine Bahar , Gumus Dogan Derya , Ozalp Akin Ezgi , Buyukavci Akif , Akpinar Funda , Hayran Gamze , Arslan Necati , Doganay Beyza , Ozturk Ertem Ilgi 
Published: October 2020

ABSTRACT:

Objective:
To inform professionals pioneering developmental-behavioral pediatrics (DBP) services in low- and middle-income countries (LMICs), we aimed to examine referral trends in 2 pioneering DBP centers at different locations in Turkey and to ascertain whether the official establishment of DBP as a subspecialty affected these trends.

Method:
This longitudinal observational study included all children referred to Ankara (AUDPD) and Inonu (IUDPD) Universities' Developmental Pediatrics Divisions between 2010 and 2018. We examined the sources of referrals and the independent effects of time and the establishment of DBP as a subspecialty on referral volume using Negative Binomial Regression (NBR) models.

Results:
Of 8,051 children, most were boys (58%) and under 24 months of age (72%). Most referrals were from the pediatric and pediatric surgery department clinics (85%); less than 1% were from child and adolescent psychiatry, and none were from family physicians. The NBR models showed that yearly, the referral volume increased significantly, 1.18-fold (95% confidence interval [CI] = 1.09–1.28) and 1.48-fold (95% CI = 1.20–1.82) for AUDPD and IUDPD, respectively. Compared with the trend of referrals before, the trend after the establishment of DBP as a subspecialty increased significantly at AUDPD, but not IUDPD.

Conclusion:
The increase in referrals to DBP over time is encouraging to professionals working to advance DBP services and training in LMICs even if DBP is not officially established as a subspecialty. Additional efforts may be needed to improve recognition and use of DBP services by community physicians and allied disciplines that provide services to children.
Focal cryoablation of atrioventricular node reentrant tachycardia: a review and comparison of data
Authors: Tomaiko Emrie , Liao Ying-Chieh , Reichert William B. , Su Wilber W. 
Published: October 2020

Purpose of review
Atrioventricular node reentrant tachycardia (AVNRT) is the most common mechanism of supraventricular tachycardia. Radiofrequency ablation has been the most prevalent method for slow pathway ablation but carries risk of atrioventricular node injury. Focal cryoablation has been utilized as an alternative ablation modality; however, there has been concern about decreased efficacy, resulting in a higher rate of recurrence postablation. We also report outcomes from two international centers using an 8-mm cryocatheter and complete a thorough comparison of existing data on ablation of AVNRT.

Recent findings
Previous reviews included studies from 2006 onward. These studies included use of the 4 mm focal cryocatheter, which has largely been abandoned in current adult practice. We will cite more contemporary studies within the past 10 years, which also includes use of the 6 and 8 mm cryocatheter.

Summary
The use of focal cryoablation allows for reversible injury during AVNRT ablation, providing safety from permanent atrioventricular node injury. With the appropriate ablation endpoints, 8 mm focal cryoablation is more effective for permanent lesion formation, leading to lower recurrences.
SIX MONTHS PRIMARY SUCCESS RATE FOR RETINAL DETACHMENT BETWEEN VITRECTOMY AND SCLERAL BUCKLING
Authors: Koto Takashi , Kawasaki Ryo , Yamakiri Keita , Baba Takayuki , Nishitsuka Koichi , Hirakata Akito , Sakamoto Taiji ,   on behalf of the Japan-Retinal Detachment Registry Group
Published: October 2020

Purpose:
To compare clinical outcomes between pars plana vitrectomy (PPV), scleral buckling (SB), and PPV+SB for rhegmatogenous retinal detachment in the Japan-RD Registry.

Methods:
This is a nation-wide, multicenter, observational study based on the registry data between 2016 and 2017. The failure levels were defined as Level 1 (a failure of retinal detachment repair), Level 2 (remaining silicone oil), and Level 3 (multiple surgeries to achieve reattachment). We compared cases treated by SB or PPV in the subgroup of simple rhegmatogenous retinal detachment using multivariate Cox proportional hazard models.

Results:
A total of 2,775 cases were included. Overall, 6 months any levels of failure in total, SB, PPV, and PPV+SB were 9.2% (n = 256), 6.9% (n = 48), 8.2% (n = 157), and 21.3% (n = 51), respectively. Poor visual acuity at baseline in SB and inferior rhegmatogenous retinal detachment and larger retinal tear in PPV were associated with a higher risk of failure. Pars plana vitrectomy was associated with a higher chance of achieving primary success in cases with simple RRD, especially for cases with superior RRD (adjusted hazard ratio 3.61, 95% confidence interval 2.22–5.94, P < 0.001).

Conclusion:
In this nationwide study, surgical anatomic outcomes were equally successful in either SB or PPV. There were different baseline characteristics associated with primary success between SB and PPV.
Sex- and age-specific genetic analysis of chronic back pain
Authors: Freidin Maxim B. , Tsepilov Yakov A. , Stanaway Ian B. , Meng Weihua , Hayward Caroline , Smith Blair H. , Khoury Samar , Parisien Marc , Bortsov Andrey , Diatchenko Luda , Børte Sigrid , Winsvold Bendik S. , Brumpton Ben M. , Zwart John-Anker ,   HUNT All-In Pain, Aulchenko Yurii S. , Suri Pradeep , Williams Frances M.K. 
Published: October 2020

Abstract
Sex differences for chronic back pain (cBP) have been reported, with females usually exhibiting greater morbidity, severity, and poorer response to treatment. Genetic factors acting in an age-specific manner have been implicated but never comprehensively explored. We performed sex- and age-stratified genome-wide association study and single nucleotide polymorphism-by-sex interaction analysis for cBP defined as “Back pain for 3+ months” in 202,077 males and 237,754 females of European ancestry from UK Biobank. Two and 7 nonoverlapping genome-wide significant loci were identified for males and females, respectively. A male-specific locus on chromosome 10 near SPOCK2 gene was replicated in 4 independent cohorts. Four loci demonstrated single nucleotide polymorphism-by-sex interaction, although none of them were formally replicated. Single nucleotide polymorphism-explained heritability was higher in females (0.079 vs 0.067, P = 0.006). There was a high, although not complete, genetic correlation between the sexes (r = 0.838 ± 0.041, different from 1 with P = 7.8E-05). Genetic correlation between the sexes for cBP decreased with age (0.858 ± 0.049 in younger people vs 0.544 ± 0.157 in older people; P = 4.3E-05). There was a stronger genetic correlation of cBP with self-reported diagnosis of intervertebral disk degeneration in males than in females (0.889 vs 0.638; P = 3.7E-06). Thus, the genetic component of cBP in the UK Biobank exhibits a mild sex- and age-dependency. This provides an insight into the possible causes of sex- and age-specificity in epidemiology and pathophysiology of cBP and chronic pain at other anatomical sites.
Different forms of traumatic brain injuries cause different tactile hypersensitivity profiles
Authors: Wattiez Anne-Sophie , Castonguay William C. , Gaul Olivia J. , Waite Jayme S. , Schmidt Chantel M. , Reis Alyssa S. , Rea Brandon J. , Sowers Levi P. , Cintrón-Pérez Coral J. , Vázquez-Rosa Edwin , Pieper Andrew A. , Russo Andrew F. 
Published: October 2020

Abstract
Chronic complications of traumatic brain injury represent one of the greatest financial burdens and sources of suffering in the society today. A substantial number of these patients suffer from posttraumatic headache (PTH), which is typically associated with tactile allodynia. Unfortunately, this phenomenon has been understudied, in large part because of the lack of well-characterized laboratory animal models. We have addressed this gap in the field by characterizing the tactile sensory profile of 2 nonpenetrating models of PTH. We show that multimodal traumatic brain injury, administered by a jet-flow overpressure chamber that delivers a severe compressive impulse accompanied by a variable shock front and acceleration–deceleration insult, produces long-term tactile hypersensitivity and widespread sensitization. These are phenotypes reminiscent of PTH in patients, in both cephalic and extracephalic regions. By contrast, closed head injury induces only transient cephalic tactile hypersensitivity, with no extracephalic consequences. Both models show a more severe phenotype with repetitive daily injury for 3 days, compared with either 1 or 3 successive injuries in a single day, providing new insight into patterns of injury that may place patients at a greater risk of developing PTH. After recovery from transient cephalic tactile hypersensitivity, mice subjected to closed head injury demonstrate persistent hypersensitivity to established migraine triggers, including calcitonin gene-related peptide and sodium nitroprusside, a nitric oxide donor. Our results offer the field new tools for studying PTH and preclinical support for a pathophysiologic role of calcitonin gene-related peptide in this condition.
Impact of a policy change restricting access to codeine on prescription opioid-related emergency department presentations: an interrupted time series analysis
Authors: Elphinston Rachel A. , Connor Jason P. , de Andrade Dominique , Hipper Linda , Freeman Chris , Chan Gary , Sterling Michele 
Published: October 2020

Abstract
Codeine is one of the most commonly used opioid analgesics. Significant codeine-related morbidity and mortality prompted regulatory responses, with the up-scheduling of codeine combination analgesics to prescription-only medicines implemented in Australia in February 2018. This study investigated the impact of codeine up-scheduling on the number of codeine and other (noncodeine) prescription opioid-related emergency department (ED) presentations in a large metropolitan tertiary hospital. Clinical features of these presentations were also examined. Interrupted time series analyses assessed monthly changes in ED presentations from June 2016 to November 2019. In the month immediately after up-scheduling, there was a significant reduction of 3.97 codeine-related presentations (B = −3.97, P = 0.022), indicating a 29.66% level change, followed by a significant change in trend to fewer monthly codeine-related presentations (B = −0.38, P = 0.005). Noncodeine prescription opioid-related (B = −1.90, P = 0.446) and ED presentations overall (B = −118.04, P = 0.140) remained unchanged immediately post-up-scheduling, with a significant change in trend from upward to downward for noncodeine (B = −0.76; P = 0.002) and ED presentations overall (B = −19.34, P = 0.022). A significant reduction of 4.58 (B = −4.58, P = 0.009) in codeine presentations involving subsequent hospital admission immediately post-up-scheduling was found; but no immediate reduction in codeine-related suicide-related overdoses, length of inpatient stay, or re-presentations (P > 0.0125; adjusted for multiple comparisons). Restricting supply of codeine to prescription-only may have resulted in less harmful codeine-related use in the community, without a corresponding immediate decrease in other opioid-related harms.
Sexual dimorphism in the nociceptive effects of hyaluronan
Authors: Bonet Ivan J.M. , Green Paul G. , Levine Jon D. 
Published: October 2020

Abstract
Intradermal administration of low-molecular-weight hyaluronan (LMWH) in the hind paw induced dose-dependent (0.1, 1, or 10 µg) mechanical hyperalgesia of similar magnitude in male and female rats. However, the duration of LMWH hyperalgesia was greater in females. This sexual dimorphism was eliminated by bilateral ovariectomy and by intrathecal administration of an oligodeoxynucleotide (ODN) antisense to the G-protein-coupled estrogen receptor (GPR30) mRNA in females, indicating estrogen dependence. To assess the receptors at which LMWH acts to induce hyperalgesia, LMWH was administered to groups of male and female rats that had been pretreated with ODN antisense (or mismatch) to the mRNA for 1 of 3 hyaluronan receptors, cluster of differentiation 44 (CD44), toll-like receptor 4, or receptor for hyaluronan-mediated motility (RHAMM). Although LMWH-induced hyperalgesia was attenuated in both male and female rats pretreated with ODN antisense for CD44 and toll-like receptor 4 mRNA, RHAMM antisense pretreatment only attenuated LMWH-induced hyperalgesia in males. Oligodeoxynucleotide antisense for RHAMM, however, attenuated LMWH-induced hyperalgesia in female rats treated with ODN antisense to GPR30, as well as in ovariectomized females. Low-molecular-weight hyaluronan–induced hyperalgesia was significantly attenuated by pretreatment with high-molecular-weight hyaluronan (HMWH) in male, but not in female rats. After gonadectomy or treatment with ODN antisense to GPR30 expression in females, HMWH produced similar attenuation of LMWH-induced hyperalgesia to that seen in males. These experiments identify nociceptors at which LMWH acts to produce mechanical hyperalgesia, establishes estrogen dependence in the role of RHAMM in female rats, and establishes estrogen dependence in the inhibition of LMWH-induced hyperalgesia by HMWH.
Trauma-focused cognitive behavioural therapy and exercise for chronic whiplash with comorbid posttraumatic stress disorder: a randomised controlled trial
Authors: Andersen Tonny Elmose , Ravn Sophie Lykkegaard , Armfield Nigel , Maujean Annick , Requena Simone Scotti , Sterling Michele 
Published: October 2020

Abstract
Many people with chronic whiplash-associated disorders (WAD) have also symptoms of posttraumatic stress disorder (PTSD), but this is rarely considered in usual predominantly exercise-based interventions. We aimed to investigate the effectiveness of combined trauma-focused cognitive behavioural therapy (TF-CBT) and exercise compared with supportive therapy (ST) and exercise for people with chronic WAD and PTSD. A randomised controlled multicentre trial with concealed allocation, assessor blinding, and blinded analysis was conducted. One hundred three participants with chronic WAD (>3 months and <5 years, grade II) and PTSD were randomised to TF-CBT and exercise (n = 53) or ST and exercise (n = 50). Both interventions comprised 10 weeks of TF-CBT or ST, followed by 6 weeks of exercise. Outcomes were measured at baseline, 10, 16 weeks, 6, and 12 months after randomisation. Analysis was intention to treat using linear mixed models. There was no difference between the interventions on the primary outcome of neck pain–related disability at any time point. At 16 weeks, the treatment effect on the 0 to 100 Neck Disability Index was 0.59 (95% confidence interval [CI] 5.51 to −4.33), at 6 months 1.18 (95% CI 6.15 to −3.78), and at 12 months 1.85 (95% CI 6.81 to −3.11). In addition, there was no difference between the interventions for most secondary outcomes at any time. Exceptions were in favour of TF-CBT and exercise, where improvements in PTSD symptoms were found at 16 weeks. From 16 weeks onwards, both groups achieved a clinically important improvement in neck pain–related disability. However, both groups remained moderately disabled.
Determinants of amino acid bioavailability from ingested protein in relation to gut health
Authors: Gaudichon Claire , Calvez Juliane 
Published: October 2020

Purpose of review
The current review provides an update on the recent research developments regarding amino acid bioavailability in conditions of both good health and gut disorders.

Recent findings
Determination of amino acid bioavailability is complex and invasive. Minimally invasive methods using stable isotopes have been developed for humans. Data were collected in different models – humans, pigs and rats with various procedures – leading to interstudy variability. They mainly focused on either plant protein or the effect of food processing on animal protein. Plant protein in their original food matrix (legumes, grains, nuts) are generally less digestible (about 80%) than animal protein (meat, egg, milk; about 93%). Food processing has a limited impact on animal protein but its effect might be higher on plant protein. Few studies have documented the effect of gut disorders on protein digestibility, except in gastric bypass where paradoxical effects were reported. Data are needed to identify the amplitude of protein malabsorption in diseases such as inflammatory bowel disease or environmental enteric dysfunction.

Summary
The past 5 years have seen a renewed interest in amino acid bioavailability in view of assessing protein quality to support current shifts in protein sourcing. Methodological developments have been performed and several studies have reported values in various models. The question of protein digestibility in gut disorders remains poorly addressed.