bluuebunny/crossref_metadata_2025 huggingface dataset:
The West Anatolian Contact Zone
Authors: Rutherford Ian
Published: October 2020

Chapter 6 looks at the religious traditon of the W. Anatolia state of Arzawa and its religon to Greek religion. The main evidence for Arzawan religious is a group of plague- and purufcation- rituals, many of them designed for military use. The authors of the rituals are said to be augurs, which shows that augury/bird-oracles were part of the procedure. In the chapter I explore parallels with Greek religion, e.g. a plague ritual in Homer, the scapegoat- (pharmakos-) rituals of Ionia and Greek bird-oracles.
Becoming Cybele
Authors: Rutherford Ian
Published: October 2020

This chapter examines a third major contact zone in NW Turkey around the 7th-century BC. Here Greek colonists established themselves and will have come into contact with the Phrygian population, who took over the area previously occupied by the Hittites in the early Iron Age. Links between Phrygians and Greeks could be much older, perhaps going back to a time before the Phrygians migrated into Anatolia. NW Turkey is the most likely context for the transmission to Greece of the cult of the goddess whom the Greeks knew as Phrygian Cybele, although her divine personality may in fact owe a good deal to Greek ideas of the Great Mother. The question arises whether or not Phrygian Cybele owes something to the Hittite religion of five centuries before.
Anaconda
Authors: Rivas Jesús A.
Published: October 2020

Written by Jesús Rivas, the undisputed expert on the biology of anacondas, this is the first authoritative book on the biology of the green anaconda, the world’s largest snake. Rivas describes his experiences over a quarter of a century exploring the secret life of these fantastic snakes, including their diet, movement patterns, life and tribulations, survival, behavior, and fascinating reproductive life. But more than just presenting facts about anacondas, Rivas tells his story about studying them in the field. Ultimately, his love for anacondas and his unorthodox approach give his voice a unique accent that makes this book stand out among other books of its kind. The rich photography and its storytelling approach make this an enjoyable and thoroughly readable book that can sit as comfortably on a coffee table as in the bookshelves of advanced scholars.
Return of Results in Population Studies: How Do Participants Perceive Them?
Authors: Nobile Hélène , Borry Pascal , Moldenhauer Jennifer , Bergmann Manuela M
Published: October 2020

As a cornerstone of public health, epidemiology has lately undergone substantial changes enabled by, among other factors, the use of biobank infrastructures. In biobank-related research, the return of results to participants constitutes an important and complex ethical question. In this study, we qualitatively investigated how individuals perceive the results returned following their participation in cohort studies with biobanks. In our semi-structured interviews with 31 participants of two such German studies, we observed that some participants overestimate the nature of the personal information they will receive from the study. Although this misestimation does not seem to jeopardize the validity of the consent provided at recruitment, it may still represent a threat for participants’ trust in research and thus their long-term commitment, crucial for such studies. We argue that such misestimation may have ethical consequences on the principles guiding the reflection on the return of results in biobank research, i.e. autonomy, beneficence, non-maleficence and reciprocity. We suggest that shifting from the idea of directly benefiting participants through the return of research results could help focusing on benefiting society as a whole, thereby increasing research trustworthiness of population-based studies using biobanks.
High Prevalence of Perineural Cysts in Patients with Fibromyalgia and Chronic Fatigue Syndrome
Authors: Hulens Mieke , Bruyninckx Frans , Dankaerts Wim , Rasschaert Ricky , De Mulder Peter , Stalmans Ingeborg , Vansant Greet , Bervoets Chris
Published: October 2020

Objective

Pain in fibromyalgia (FM) and chronic fatigue syndrome (CFS) is assumed to originate from central sensitization. Perineural cysts or Tarlov cysts (TCs) are nerve root dilations resulting from pathologically increased cerebrospinal fluid pressure. These cysts initially affect sensory neurons and axons in dorsal root ganglia and produce sensory symptoms (pain and paresthesia). Symptomatic TC (STC) patients often complain about widespread pain and fatigue. Consequently, STC patients may initially be diagnosed with FM, CFS, or both. The objective of this study was to document the prevalence of TCs in patients diagnosed with FM or CFS.

Design

A retrospective study.

Setting

An outpatient clinic for musculoskeletal disorders.

Subjects

Patients diagnosed with FM according to the 1990 American College of Rheumatology criteria or with CFS according to the 1994 Centers for Disease Control criteria were selected.

Methods

Review of lumbar and sacral magnetic resonance imaging scans including TCs ≥5 mm in size.

Results

In total, 197 patients with FM, CFS, or both underwent magnetic resonance imaging. Ninety-one percent were women. The mean age was 48.1 (±11.9) years. TCs were observed in 39% of patients, with a mean size of 11.8 (±5.2) mm. In males, the prevalence was 12%, vs. 42% in females.

Conclusions

In patients diagnosed with FM or CFS, the prevalence of TCs was three times higher than that in the general population. This observation supports the hypothesis that STCs, FM, and CFS may share the same pathophysiological mechanism, i.e., moderately increased cerebrospinal fluid pressure, causing irritation of neurons and axons in dorsal root ganglia.
Beyond synchrony: the capacity of fMRI hyperscanning for the study of human social interaction
Authors: Misaki Masaya , Kerr Kara L , Ratliff Erin L , Cosgrove Kelly T , Simmons W Kyle , Morris Amanda Sheffield , Bodurka Jerzy
Published: October 2020

Hyperscanning—simultaneous brain scanning of two or more individuals—holds great promise in elucidating the neurobiological underpinnings of social cognitive functions. This article focuses on functional magnetic resonance imaging (fMRI) hyperscanning and identifies promising targets for studying the neuroscience of social interaction with fMRI hyperscanning. Specifically, we present applications of fMRI hyperscanning in the study of social interaction along with promising analysis approaches for fMRI hyperscanning, with its high spatial and low temporal resolution. We first review fMRI hyperscanning studies in social neuroscience and evaluate the premise of using this costly neuroimaging paradigm. Many second-person social neuroscience studies are possible without fMRI hyperscanning. However, certain fundamental aspects of social cognition in real-life social interactions, including different roles of interactors, shared intention emerging through interaction and history of interaction, can be addressed only with hyperscanning. We argue that these fundamental aspects have not often been investigated in fMRI hyperscanning studies. We then discuss the implication of the signal coupling found in fMRI hyperscanning and consider analysis approaches that make fair use of it. With fMRI hyperscanning, we can explore not only synchronous brain activations but whole-brain asymmetric activation patterns with a lagged association between interacting individuals.
Predictive Performance of Exposome Score for Schizophrenia in the General Population
Authors: Pries Lotta-Katrin , Erzin Gamze , van Os Jim , ten Have Margreet , de Graaf Ron , van Dorsselaer Saskia , Bak Maarten , Rutten Bart P F , Guloksuz Sinan
Published: October 2020

Previously, we established an estimated exposome score for schizophrenia (ES-SCZ) as a cumulative measure of environmental liability for schizophrenia to use in gene–environment interaction studies and for risk stratification in population cohorts. Hereby, we examined the discriminative function of ES-SCZ for identifying individuals diagnosed with schizophrenia spectrum disorder in the general population by measuring the area under the receiver operating characteristic curve (AUC). Furthermore, we compared this ES-SCZ method to an environmental sum score (Esum-SCZ) and an aggregate environmental score weighted by the meta-analytical estimates (Emet-SCZ). We also estimated ORs and Nagelkerke’s R2 for ES-SCZ in association with psychiatric diagnoses and other medical outcomes. ES-SCZ showed a good discriminative function (AUC = 0.84) and statistically significantly performed better than both Esum-SCZ (AUC = 0.80) and Emet-SCZ (AUC = 0.80). At optimal cut point, ES-SCZ showed similar performance in ruling out (LR− = 0.20) and ruling in (LR+ = 3.86) schizophrenia. ES-SCZ at optimal cut point showed also a progressively greater magnitude of association with increasing psychosis risk strata. Among all clinical outcomes, ES-SCZ was associated with schizophrenia diagnosis with the highest OR (2.76, P < .001) and greatest explained variance (R2 = 14.03%), followed by bipolar disorder (OR = 2.61, P < .001, R2 = 13.01%) and suicide plan (OR = 2.44, P < .001, R2 = 12.44%). Our findings from an epidemiologically representative general population cohort demonstrate that an aggregate environmental exposure score for schizophrenia constructed using a predictive modeling approach—ES-SCZ—has the potential to improve risk prediction and stratification for research purposes and may help gain insight into the multicausal etiology of psychopathology.
Tungsten Increases Sex-Specific Osteoclast Differentiation in Murine Bone
Authors: Chou Hsiang , Grant Michael P , Bolt Alicia M , Guilbert Cynthia , Plourde Dany , Mwale Fackson , Mann Koren K
Published: October 2020

Tungsten is a naturally occurring metal that is increasingly used in industry and medical devices, and is labeled as an emerging environmental contaminant. Like many metals, tungsten accumulates in bone. Our previous data indicate that tungsten decreases differentiation of osteoblasts, bone-forming cells. Herein, we explored the impact of tungsten on osteoclast differentiation, which function in bone resorption. We observed significantly elevated osteoclast numbers in the trabecular bone of femurs following oral exposure to tungsten in male, but not female mice. In order to explore the mechanism(s) by which tungsten increases osteoclast number, we utilized in vitro murine primary and cell line pre-osteoclast models. Although tungsten did not alter the adhesion of osteoclasts to the extracellular matrix protein, vitronectin, we did observe that tungsten enhanced RANKL-induced differentiation into tartrate-resistant acid phosphatase (TRAP)-positive mononucleated osteoclasts. Importantly, tungsten alone had no effect on differentiation or on the number of multinucleated TRAP-positive osteoclasts. Enhanced RANKL-induced differentiation correlated with increased gene expression of differentiated osteoclast markers Nfatc1, Acp5, and Ctsk. Although tungsten did not alter the RANK surface receptor expression, it did modulate its downstream signaling. Co-exposure of tungsten and RANKL resulted in sustained positive p38 signaling. These findings demonstrate that tungsten enhances sex-specific osteoclast differentiation, and together with previous findings of decreased osteoblastogenesis, implicate tungsten as a modulator of bone homeostasis.
Spatiotemporal clustering, social inequities and the risk of leptospirosis in an endemic area of Brazil: a retrospective spatial modelling
Authors: de Souza Katyucia O C , Góes José Augusto P , Melo Matheus S , Leite Paula M G , Andrade Lucas A , Góes Marco Aurélio de O , Ribeiro Caíque J N , Araújo Damião da C , de Menezes Andreia F , dos Santos Allan D
Published: October 2020

Background

Leptospirosis is an endemic disease in Brazil of social and economic relevance related to behavioural and socioenvironmental factors. This study aimed to analyse the spatiotemporal distribution of the incidence of leptospirosis and its association with social determinants in health in a state of northeastern Brazil.

Methods

An ecological study of temporal series with techniques of spatial analysis using secondary data of the cases of leptospirosis notified in the Information System of Notifiable Diseases of the state of Sergipe (2008–2017) was conducted. The analysis of temporal trends was performed using Poisson regression. Spatial analyses were performed using the Moran index, the local empirical Bayesian model, scan statistics and spatial regression.

Results

The incidence rate decreased from 3.66 to 1.44 cases per 100 000 inhabitants in 2008 and 2017, respectively. Leptospirosis was associated with social inequities, mostly affecting males aged 20–49 y living in urban areas. The space-time scan indicated the formation of a risk cluster in municipalities in the metropolitan region of the state.

Conclusions

The data indicated the persistence of leptospirosis transmission, maintaining a pattern of high endemicity in some municipalities associated with social inequities. The study showed the temporal and spatial dynamics of the disease to better target specific actions for prevention and control.
Recognizing and treating five common dermatologic conditions seen in primary care
Authors: Etcheverria Eden
Published: October 2020

Skin conditions are one of the most common chief complaints encountered in the primary care setting. Primary care providers (PCPs) may not have not received enough exposure and education on dermatologic conditions. Of all skin conditions, atopic dermatitis, acne vulgaris, cellulitis/abscess, verruca vulgaris, and benign skin lesions are typically the most common to present in the primary care setting. PCPs must be well educated on these topics and confident in their diagnostic and management skills. This article reviews the five most common skin conditions encountered in primary care so that PCPs can reduce the number of referrals to dermatology for conditions that can easily be managed by PCPs.
Travel Medicine
Authors: Rosenbaum Alan J. , Stringer Jeffrey S. A.
Published: October 2020

Travel is an increasingly common aspect of modern life, and the practicing obstetrician–gynecologist needs a good understanding of the health- and safety-related issues it presents for patients. This monograph examines the environmental data that support individual risk assessment and provides guidance on how to eliminate or mitigate those risks, including recommendations for immunization and chemoprophylaxis for women traveling to areas with endemic infectious disease. Management approaches for travel-related diseases, such as traveler’s diarrhea, altitude sickness, and location-specific diseases, are reviewed as are special considerations for pregnant and breastfeeding women and women who are attempting pregnancy. Evaluation and management of the returned traveler also is addressed. The recommendations in this document cite resources available from the United States federal government; therefore, they are applicable to women seeking care in the United States.
Accuracy of Patient-Specific 3D-Printed Drill Guides for Pedicle and Lateral Mass Screw Insertion
Authors: Pijpker Peter A.J. , Kraeima Joep , Witjes Max J.H. , Oterdoom D.L. Marinus , Vergeer Rob A. , Coppes Maarten H. , Groen Rob J.M. , Kuijlen Jos M.A.
Published: October 2020

Study Design.

Single-center retrospective case series.

Objective.

The purpose of this study was to assess the safety and accuracy of three-dimensional (3D)-printed individualized drill guides for pedicle and lateral mass screw insertion in the cervical and upper-thoracic region, by comparing the preoperative 3D surgical plan with the postoperative results.

Summary of Background Data.

Posterior spinal fusion surgery can provide rigid intervertebral fixation but screw misplacement involves a high risk of neurovascular injury. However, modern spine surgeons now have tools such as virtual surgical planning and 3D-printed drill guides to facilitate spinal screw insertion.

Methods.

A total of 15 patients who underwent posterior spinal fusion surgery involving patient-specific 3D-printed drill guides were included in this study. After segmentation of bone and screws, the postoperative models were superimposed onto the preoperative surgical plan. The accuracy of the realized screw trajectories was quantified by measuring the entry point and angular deviation.

Results.

The 3D deviation analysis showed that the entry point and angular deviation over all 76 screw trajectories were 1.40 ± 0.81 mm and 6.70 ± 3.77°, respectively. Angular deviation was significantly higher in the sagittal plane than in the axial plane (P = 0.02). All screw positions were classified as “safe” (100%), showing no neurovascular injury, facet joint violation, or violation of the pedicle wall.

Conclusions.

3D virtual planning and 3D-printed patient-specific drill guides appear to be safe and accurate for pedicle and lateral mass screw insertion in the cervical and upper-thoracic spine. The quantitative 3D deviation analyses confirmed that screw positions were accurate with respect to the 3D-surgical plan.

Level of Evidence: 4
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.

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.

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

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.

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.
Ambulatory continuous peripheral nerve blocks to treat postamputation phantom limb pain: a multicenter, randomized, quadruple-masked, placebo-controlled clinical trial
Authors: Ilfeld Brian M. , Khatibi Bahareh , Maheshwari Kamal , Madison Sarah J. , Esa Wael Ali Sakr , Mariano Edward R. , Kent Michael L. , Hanling Steven , Sessler Daniel I. , Eisenach James C. , Cohen Steven P. , Mascha Edward J. , Ma Chao , Padwal Jennifer A. , Turan Alparslan ,   the PAINfRE Investigators
Published: October 2020

Phantom limb pain is thought to be sustained by reentrant neural pathways, which provoke dysfunctional reorganization in the somatosensory cortex. We hypothesized that disrupting reentrant pathways with a 6-day-long continuous peripheral nerve block reduces phantom pain 4 weeks after treatment. We enrolled patients who had an upper- or lower-limb amputation and established phantom pain. Each was randomized to receive a 6-day perineural infusion of either ropivacaine or normal saline. The primary outcome was the average phantom pain severity as measured with a Numeric Rating Scale (0-10) at 4 weeks, after which an optional crossover treatment was offered within the following 0 to 12 weeks. Pretreatment pain scores were similar in both groups, with a median (interquartile range) of 5.0 (4.0, 7.0) for each. After 4 weeks, average phantom limb pain intensity was a mean (SD) of 3.0 (2.9) in patients given local anesthetic vs 4.5 (2.6) in those given placebo (difference [95% confidence interval] 1.3 [0.4, 2.2], P = 0.003). Patients given local anesthetic had improved global impression of change and less pain-induced physical and emotional dysfunction, but did not differ on depression scores. For subjects who received only the first infusion (no self-selected crossover), the median decrease in phantom limb pain at 6 months for treated subjects was 3.0 (0, 5.0) vs 1.5 (0, 5.0) for the placebo group; there seemed to be little residual benefit at 12 months. We conclude that a 6-day continuous peripheral nerve block reduces phantom limb pain as well as physical and emotional dysfunction for at least 1 month.
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

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

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

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

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

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.

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.
Donor-specific antibodies in liver transplantation: challenges in diagnosis and determining clinical impact
Authors: Kim Steven C. , Foley David P.
Published: October 2020

Purpose of review

Our understanding of the clinical impact of donor-specific antibodies in liver transplant recipients has evolved in recent years as outcomes for liver allografts have improved and advances in diagnostic testing have made recognition of antibody mediated rejection in transplant patients more sensitive.

Recent findings

Two main types of donor-specific antibodies – preformed and de novo – have been reported in the literature to have a negative impact on graft survival, and researchers have been able to further identify subclasses of class II donor-specific antibodies as being the most clinically impactful. Furthermore, there is evidence that donor-specific antibody formation can augment cellular rejection in liver grafts and lead to worsened clinical outcomes. Recent data have shown a higher prevalence of donor-specific antibody formation than previously reported.

This review explores the most recent literature regarding the clinical impact of both preformed and de-novo donor-specific antibodies and potential management guidelines for patients undergoing liver transplantation. The best practice guidelines for undergoing monitoring for donor-specific antibody formation and protocol biopsies in sensitized patients will depend on further multiinstitutional studies.
The use of organs from hepatitis C virus-viremic donors into uninfected recipients
Authors: Kahn Jeffrey A.
Published: October 2020

Purpose of review

There has been an ongoing disparity between the number of organs available for solid organ transplantation (SOT) relative to the need. This has resulted in significant waitlist mortality, may affect transplant outcomes due to transplants being performed on sicker patients and may even increase healthcare costs due to extended hospital stays. Transplanting organs from hepatitis C virus (HCV)-infected donors into uninfected recipients (D+/R−) is now a reality, due to the advent of highly affective direct-acting antivirals (DAAs) which not only have very high efficacy, but also a favorable side effect and drug–drug interaction profile.

Recent findings

Data from multiple centers reporting outcomes of kidney, liver, heart, lung and liver-kidney transplant during the past few years reveal that SOT from HCV-infected donors into noninfected recipients is safe, efficacious and can result in excellent recipient outcomes, with an opportunity to decrease the time on the waitlist, waitlist mortality and to improve outcomes after transplant due to less morbidity at the time of surgery. When livers are the transplanted organ, 8–12 weeks of DAA treatment will be required. For other organs, 2–4 weeks is likely sufficient. The available DAAs have profiles such that patients with all genotypes, with or without renal insufficiency an on renal replacement therapy and those who fail treatment may be successfully treated, with a sustained virologic response rate of more than 95%. Based upon the available data, starting DAAs shortly after transplant will likely limit posttransplant complications. that This will require cooperation between the transplant team, transplant hospital and insurer providing medication coverage.

SOT from HCV infected recipients is safe, is associated with excellent outcomes and should be considered for recipients who would benefit from receiving an organ earlier than they would if they waited for an organ from an uninfected donor.