bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase II study of dose-dense temozolomide and lapatinib for recurrent low-grade and anaplastic supratentorial, infratentorial, and spinal cord ependymoma
Authors: Gilbert Mark R , Yuan Ying , Wu Jimin , Mendoza Tito , Vera Elizabeth , Omuro Antonio , Lieberman Frank , Robins H Ian , Gerstner Elizabeth R , Wu Jing , Wen Patrick Y , Mikkelsen Tom , Aldape Kenneth , Armstrong Terri S
Published: October 2020

Background

No standard medical treatment exists for adult patients with recurrent ependymoma, and prospective clinical trials in this population have not succeeded because of its rarity and challenges in accruing patients. The Collaborative Ependymoma Research Network conducted a prospective phase II clinical trial of dose-dense temozolomide (TMZ) and lapatinib, targeting the unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter status and increased expression of ErbB2 (human epidermal growth factor receptor 2) and ErbB1 (epidermal growth factor receptor) in ependymomas.

Methods

Patients age 18 or older with histologically proven and progressive ependymoma or anaplastic ependymoma were eligible and received dose-dense TMZ and daily lapatinib. The primary outcome measure was median progression-free survival (PFS). Landmark 6- and 12-month PFS and objective response were measured. Serial assessments of symptom burden using the MD Anderson Symptom Inventory Brain Tumor (MDASI-BT)/MDASI–Spine Tumor modules were collected.

Results

The 50 patients enrolled had a median age of 43.5 years, median Karnofsky performance status of 90, and a median of 2 prior relapses. Twenty patients had grade III, 16 grade II, and 8 grade I ependymoma. Half had spinal cord tumors; 15 had a supratentorial tumor, 8 infratentorial, and 2 had disseminated disease. Treatment was well tolerated. The median PFS was 7.8 months (95% CI: 5.5,12.2); the 6- and 12-month PFS rates were 55% and 38%, with 2 complete and 6 partial responses. Measures of symptom burden showed reduction in moderate-severe pain and other disease-related symptoms in most patients.

Conclusions

This treatment, with demonstrated clinical activity with objective responses and prolonged disease control associated with disease-related symptom improvements, is an option as a salvage regimen for adult patients with recurrent ependymoma.
Gender, achievement, and subject choice in English education
Authors: Cavaglia Chiara , Machin Stephen , McNally Sandra , Ruiz-Valenzuela Jenifer
Published: October 2020

In common with other OECD countries, there is a gender gap in educational achievement in England favouring girls. This carries through to tertiary education. On the other hand, boys are far more likely to engage in STEM in post-16 vocational education and at university. The underachievement of boys overall, but over-representation in STEM, presents significant challenges for policy. This paper documents changes in the gender gap over the last 20 years in England and discusses findings in the light of international evidence. It concludes that education policies, in academic and in vocational spheres, can be designed to reduce gender inequalities that exist in both.
Banking, Trade, and the Making of a Dominant Currency
Authors: Gopinath Gita , Stein Jeremy C
Published: October 2020

We explore the interplay between trade-invoicing patterns and the pricing of safe assets in different currencies. Our theory highlights the following points: (i) a currency’s role as a unit of account for invoicing decisions is complementary to its role as a safe store of value; (ii) this complementarity can lead to the emergence of a single dominant currency in trade invoicing and global banking, even when multiple large candidate countries share similar economic fundamentals; (iii) firms in emerging-market countries endogenously take on currency mismatches by borrowing in the dominant currency; and (iv) the expected return on dominant-currency safe assets is lower than that on similarly safe assets denominated in other currencies, thereby bestowing an “exorbitant privilege” on the dominant currency. The theory thus provides a unified explanation for why a dominant currency is so heavily used in both trade invoicing and in global finance.
Transformative academic institutions: An experimental framework for understanding regional impacts of research
Authors: Aranguren María José , Canto-Farachala Patricia , Wilson James R
Published: October 2020

Public and private research funding to academic institutions is increasingly conditional on demonstrating societal impact. Research is expected to produce new knowledge that is both relevant in academia and of direct practical use in society. Universities are well placed to serve as links between global academic communities and local problem owners. However, playing this pivotal role is problematic because in practice there is a tendency to frame the dual role of producing socially relevant and academic knowledge in terms of an artificial distinction between applied consultancy and basic research. Considering the challenges faced by universities in playing a more proactive role in addressing the practical challenges faced by their home regions, we propose the term transformative academic institutions to refer to research centres created within universities to proactively engage in the socioeconomic development of the regions in which they are rooted. We propose an experimental framework that can help map the relationship between their role in a global academic knowledge community and their role in the (local) practical knowledge community. The framework is developed from on our own experience working in an academic institution that conducts research to strengthen regional socioeconomic development processes. We experiment with the framework through an application to our own research context in the period 2016–19. Our findings show that this relationship can be mapped by assessing: (1) how well academic research questions are aligned to themes identified in regional policy discourse; and (2) whether academic knowledge has demonstrably led to changes actioned by regional stakeholders.
Prevalence and risk factors of relapse in patients with ANCA-associated vasculitis receiving cyclophosphamide induction: a systematic review and meta-analysis of large observational studies
Authors: He Peng , Hu Jin-ping , Tian Xiu-juan , He Li-jie , Sun Shi-ren , Huang Chen
Published: October 2020

Background

Clinical relapses are common in patients with ANCA-associated vasculitis (AAV). The aim of this systematic review was to estimate time-point prevalence and risk factors of relapse.

Methods

We searched PubMed, Embase, and Cochrane Library databases from their inception to March 30, 2020. Cohorts and post-hoc studies were included for the estimation of summary cumulative relapse rates (CRRs) and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Sensitivity and meta-regression analyses were also performed.

Results

Of the 42 eligible studies, 24 studies with 6236 participants were used for the pooled analyses of CRRs. The summary 1-year, 3-year, and 5-year CRRs were 0.12 (95% CI, 0.10–0.14), 0.33 (0.29–0.38), and 0.47 (0.42–0.52), respectively. In meta-regressions, the baseline age was positively associated with 1-year CRR. The proportion of granulomatosis with polyangiitis was positively associated with 5-year CRR. Twenty-eight studies with 5390 participants were used for the meta-analysis of risk factors for relapse, including a lower level of baseline serum creatine, proteinase 3 (PR3)-ANCA positivity at diagnosis, an ANCA rise, extrarenal organ involvement (including lung, cardiovascular, upper respiratory, and gastrointestinal involvement), intravenous (vs oral) cyclophosphamide induction, a shorter course of immunosuppressant maintenance, and maintenance with mycophenolate mofetil (vs azathioprine).

Conclusions

Our systematic review demonstrated that the 1-year, 3-year, and 5-year cumulative probabilities of relapse were ∼12%, 33%, and 47% in AAV patients receiving cyclophosphamide induction, respectively. Early identification of risk factors for relapse is helpful to the risk stratification of patients so as to achieve personalized treatment.
Incidence and predictors of severe infections in ANCA-associated vasculitis: a population-based cohort study
Authors: Rathmann Jens , Jayne David , Segelmark Mårten , Jönsson Göran , Mohammad Aladdin J
Published: October 2020

Objective

To determine the incidence rate, predictors and outcome of severe infections in a population-based cohort of ANCA-associated vasculitis (AAV).

Methods

The study included 325 cases of AAV (152 female) diagnosed from 1997 through 2016 from a defined geographic area in Sweden. All severe infection events (requiring hospitalization and treatment with intravenous antimicrobials) were identified. The Birmingham vasculitis activity score (BVAS) was used to evaluate disease activity, and organ damage was assessed using the vasculitis damage index (VDI). Patients were followed from time of AAV diagnosis to death or December 2017.

Results

A total of 129 (40%) patients suffered at least one severe infection. In 2307 person-years (PY) of follow-up, 210 severe infections were diagnosed. The incidence rate of severe infections was 9.1/100 PY and was highest during the first year following AAV diagnosis at 22.1/100 PY (P < 0.001). Pneumonia, sepsis and urinary tract infection were the most common infections. Opportunistic infections constituted only 6% of all severe infections. In Cox regression analysis age and BVAS at diagnosis were the only factors independently predicting severe infection [hazard ratio: 1.54 (P < 0.001) and 1.27 (P = 0.001), respectively]. Severe infection was associated with poorer prognosis with respect to median VDI score 12 months post-AAV diagnosis, renal survival and mortality. Severe infections were the cause of death in 32 patients (22% of all deaths).

Conclusion

. Severe infection is a common problem in AAV, with the most important prognostic factors being older age and high disease activity at diagnosis. Severe infections are associated with permanent organ damage and high mortality.
Increasing the relevance of science for practice and practice for science: Quantitative empirical insights
Authors: Binder Claudia R , Fritz Livia , Hansmann Ralph , Balthasaar Andreas , Roose Zilla
Published: October 2020

We present results of a survey conducted with researchers and practitioners involved in a Swiss National Research Programme on steering energy consumption. We analyse what motivates practitioners and researchers to engage in a collaborative research project, their perception of the collaboration intensity in different project phases, and the extent to which the research project provided useful results for practitioners. Our analyses demonstrate that the intensity of collaboration is a key driver of successful collaboration as it fosters trust between researchers and practitioners. Thereby, it increases the usefulness of the research project for practitioners and their perceived contribution to the success of the research project. Research programmes should thus (1) foster trust through incentivising collaboration between research and practice; (2) facilitate the development of a shared understanding of researchers’ and practitioners’ respective roles; and (3) support the inclusion of practitioners in the project development phase through financial support during the proposal-writing phase.
Diagnostics and the neglected tropical diseases roadmap: setting the agenda for 2030
Authors: Souza Ashley A , Ducker Camilla , Argaw Daniel , King Jonathan D , Solomon Anthony W , Biamonte Marco A , Coler Rhea N , Cruz Israel , Lejon Veerle , Levecke Bruno , Marchini Fabricio K , Marks Michael , Millet Pascal , Njenga Sammy M , Noordin Rahmah , Paulussen René , Sreekumar Esvawaran , Lammie Patrick J
Published: October 2020

Accurate and reliable diagnostic tools are an essential requirement for neglected tropical diseases (NTDs) programmes. However, the NTD community has historically underinvested in the development and improvement of diagnostic tools, potentially undermining the successes achieved over the last 2 decades. Recognizing this, the WHO, in its newly released draft roadmap for NTD 2021–2030, has identified diagnostics as one of four priority areas requiring concerted action to reach the 2030 targets. As a result, WHO established a Diagnostics Technical Advisory Group (DTAG) to serve as the collaborative mechanism to drive progress in this area. Here, the purpose and role of the DTAG are described in the context of the challenges facing NTD programmes.
Risk Factors for Proximal Junctional Kyphosis Following Surgical Deformity Correction in Pediatric Neuromuscular Scoliosis
Authors: Toll Brandon J. , Gandhi Shashank V. , Amanullah Amir , Samdani Amer F. , Janjua M. Burhan , Kong Qingwu , Pahys Joshua M. , Hwang Steven W.
Published: October 2020

Study Design.

Single-center retrospective cohort analysis.

Objective.

The aim of this study was to evaluate risk factors associated with the development of proximal junctional kyphosis (PJK) in pediatric neuromuscular scoliosis (NMS).

Summary of Background Data.

PJK is a common cause of reoperation in adult deformity but has been less well reported in pediatric NMS.

Methods.

Sixty consecutive pediatric patients underwent spinal fusion for NMS with a minimum 2-year follow-up. PJK was defined as >10° increase between the inferior end plate of the upper instrumented vertebra (UIV) and the superior end plate of the vertebra two segments above. Regression analyses as well as binary correlational models and Student t tests were employed for further statistical analysis assessing variables of primary and compensatory curve magnitudes, thoracic kyphosis, proximal kyphosis, lumbar lordosis, pelvic obliquity, shoulder imbalance, Risser classification, and sagittal profile.

Results.

The present cohort consisted of 29 boys and 31 girls with a mean age at surgery of 14 ± 2.7 years. The most prevalent diagnoses were spinal cord injury (23%) and cerebral palsy (20%). Analysis reflected an overall radiographic PJK rate of 27% (n = 16) and a proximal junctional failure rate of 7% (n = 4). No significant association was identified with previously suggested risk factors such as extent of rostral fixation (P = 0.750), rod metal type (P = 0.776), laminar hooks (P = 0.654), implant density (P = 0.386), nonambulatory functional status (P = 0.254), or pelvic fixation (P = 0.746). Significant risk factors for development of PJK included perioperative use of halo gravity traction (38%, P = 0.029), greater postoperative C2 sagittal translation (P = 0.030), decreased proximal kyphosis preoperatively (P = 0.002), and loss of correction of primary curve magnitude at follow-up (P = 0.047). Increase in lumbar lordosis from post-op to last follow-up trended toward significance (P = 0.055).

Conclusion.

Twenty-seven percent of patients with NMS developed PJK, and 7% had revision surgery. Those treated with halo gravity traction or with greater postoperative C2 sagittal translation, loss of primary curve correction, and smaller preoperative proximal kyphosis had the greatest risk of developing PJK.

Level of Evidence: 4
Neuron-Specific Enolase Levels in Adults Under Venoarterial Extracorporeal Membrane Oxygenation
Authors: Reuter Jean , Peoc’h Katell , Bouadma Lila , Ruckly Stéphane , Chicha-Cattoir Valérie , Faille Dorothée , Bourrienne Marie-Charlotte , Dupuis Claire , Magalhaes Eric , Tanaka Sébastien , Vinclair Camille , de Montmollin Etienne , Mazighi Mikael , Para Marylou , Braham Wael , Pisani Angelo , Ajzenberg Nadine , Timsit Jean-François , Sonneville Romain
Published: October 2020

Objectives:

We aimed to determine if elevations in serum neuron-specific enolase are associated with brain injury and outcomes in adults who require venoarterial extracorporeal membrane oxygenation.

Design:

Prospective observational study.

Setting:

Two ICUs of a university hospital, Paris, France.

Patients:

Consecutive adult patients treated with venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock or in-hospital refractory cardiac arrest.

Interventions:

None.

Measurements and Main Results:

Serum sampled 1, 3, and 7 days after venoarterial extracorporeal membrane oxygenation cannulation was stored at –80°C and neuron-specific enolase concentrations were measured in batches at the end of the study. The association between neuron-specific enolase concentrations and outcomes (28-d mortality and poor outcome, defined by a score of 4–6 on the modified Rankin scale at 90 d) were explored by multivariable logistic regression, with neuron-specific enolase concentrations dichotomized according to median values. One-hundred three patients were included, of whom 26 (25%) received preextracorporeal membrane oxygenation cardiopulmonary resuscitation. Median (interquartile range) day-1, day-3, and day-7 neuron-specific enolase serum concentrations were 37 μg/L (26–51 μg/L), 25 μg/L (19–37) μg/L, and 22 μg/L (17–31 μg/L). After adjustment for Simplified Acute Physiology Score II, preextracorporeal membrane oxygenation cardiopulmonary resuscitation, and Sepsis Organ Failure Assessment score at time of cannulation, a day-3 neuron-specific enolase greater than 25 μg/L remained independently associated with 28-day mortality (adjusted odds ratio, 4.98; 95% CI, 1.86–13.32) and poor outcome at 90 days (adjusted odds ratio, 4.63; 95% CI, 1.81–11.84). A day-3 neuron-specific enolase threshold greater than 80 μg/L had a 100% specificity for prediction of both mortality (95% CI, 92–100%) and poor functional outcome (95% CI, 89–100%). In a subset of patients who underwent brain CT, neuron-specific enolase concentrations were significantly higher in patients diagnosed with stroke, as compared with those without stroke.

Conclusions:

In adult patients under venoarterial extracorporeal membrane oxygenation, day-3 serum neuron-specific enolase concentrations are independently associated with short-term mortality and poor functional outcomes. These findings deserve validation in a multicenter setting.
Responding to COVID-19: lessons from Kerala on what worked under resource constraint settings and a glimpse into the surgical management of patients
Authors: Rahim Asma A. , Chacko Thomas V. , Rajan Sheeja
Published: October 2020

Background:

The outbreak of COVID-19 into a pandemic took many countries by surprise and were found wanting for their response and containment measures that they undertook and resulted in unacceptably high mortality in number terms made them search for alternative approaches and models of containment to combat the scourge. In the state of Kerala in India, the response of the government and public response was different compared with rest of the country. Its success with containment to prevent the spillover of the virus into the general public for a long period of time made other states and countries sit up and take notice.

Materials and methods:

Participatory observation in situ by the authors’ personal first hand experience in the public health and surgical practice fields enabled them to use the framework of components measures for outbreak containment following the Nipah outbreak in the state as a lens to capture the factors and measures undertaken for success in COVID-19 containment in Kerala.

Results:

Kerala ensured that a very low proportion of population got infected and a low case fatality rate of 0.94%. What worked was anticipatory preparedness of the political and health systems, systematic contact tracing and quarantine of contacts, transparency in reporting of data and dynamic data-based policy decisions. These measures when combined with social security measures for vulnerable groups, instilled a sense of solidarity with the state government’s harsh “lockdown” measures taken and thereby ensured community wide people’s participation that proved critical for the success in containment.

Conclusion:

By using the consolidated framework of components measures for outbreak containment following the Nipah outbreak in the state as a lens along with participatory observation by the authors, it was possible to capture the factors and measures undertaken for success in COVID-19 containment in Kerala.
Systematic Review of Case Reports of Poor Neonatal Outcomes With Water Immersion During Labor and Birth
Authors: Vanderlaan Jennifer , Hall Priscilla
Published: October 2020

Water immersion is a valuable comfort measure in labor, that can be used during the first or second stage of labor. Case reports of adverse outcomes create suspicion about water birth safety, which restricts the availability of water birth in the United States. The objective of this study was to synthesize the information from case reports of adverse water birth events to identify practices associated with these outcomes, and to identify patterns of negative outcomes. The research team conducted a systematic search for cases reports of poor neonatal outcomes with water immersion. Eligible manuscripts reported any adverse neonatal outcome with immersion during labor or birth; or excluded if no adverse outcome was reported or the birth reported was unattended. A qualitative narrative synthesis was conducted to identify patterns in the reports. There were 47 cases of adverse outcomes from 35 articles included in the analysis. There was a pattern of cases of Pseudomonas and Legionella, but other infections were uncommon. There were cases of unexplained neonatal hyponatremia following water birth that need further investigation to determine the mechanism that contributes to this complication. The synthesis was limited by reporting information of interest to pediatricians with little information about water birth immersion practices. These data did not support concerns of water aspiration or cord rupture, but did identify other potential risks. Water immersion guidelines need to address infection risk, optimal management of compromised water-born infants, and the potential association between immersion practice and hyponatremia.
Improving Evaluation and Treatment of Hyperbilirubinemia in Late Preterm Infants
Authors: Brown Sheila A. , Waldrop Julee , D'Auria Jennifer , Haushalter Jamie
Published: October 2020

Late preterm (LPT) infants are at an increased risk for hyperbilirubinemia. Accurate identification and early treatment are needed for optimal health outcomes. In a newborn nursery at an academic medical center, bilirubin levels were drawn at 24 hours of life, per protocol. These infants were rarely treated at this time. Rather, predischarge bilirubin levels (at about 48 hours of life) would indicate treatment, often leading to increased length of hospital stay. The practice change evaluation was conducted using retrospective medical record review. Practice change to test serum bilirubin levels at 36 hours of life rather than 24 hours of life. Compliance with the practice change was achieved (P < .05). More LPT infants were identified and treated for hyperbilirubinemia without an increase in length of stay. Readmissions for hyperbilirubinemia and blood draw rates also declined. Although more LPT infants were identified and treated for hyperbilirubinemia, there is room for improvement, and increased adherence to the policy might yield an even greater impact on quality and safety of care surrounding bilirubin management.
Revisiting matrix metalloproteinase 12: its role in pathophysiology of asthma and related pulmonary diseases
Authors: Abd-Elaziz Khalid , Jesenak Milos , Vasakova Martina , Diamant Zuzana
Published: October 2020

Purpose of review

Matrix metalloproteinases (MMPs) are a family of over 20 zinc-dependent proteases with different biological and pathological activities, and many have been implicated in several diseases. Although nonselective MMP inhibitors are known to induce serious side-effects, targeting individual MMPs may offer a safer therapeutic potential for several diseases. Hence, we provide a concise overview on MMP-12, given its association with pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and other progressive pulmonary fibrosis (PPF), which may also occur in coronavirus disease 2019.

Recent findings

In asthma, COPD, and PPF, increased MMP-12 levels have been associated with inflammation and/or structural changes within the lungs and negatively correlated with functional parameters. Increased pulmonary MMP-12 levels and MMP-12 gene expression have been related to disease severity in asthma and COPD. Targeting MMP-12 showed potential in animal models of pulmonary diseases but human data are still very scarce.

Although there may be a potential role of MMP-12 in asthma, COPD and PPF, several pathophysiological aspects await elucidation. Targeting MMP-12 may provide further insights into MMP-12 related mechanisms and how this translates into clinical outcomes; this warrants further research.
Incorporating Absolute Phagocyte Count With Absolute Neutrophil Count as a Measure for Safe Discharge for Pediatric Oncology Febrile Neutropenia: A Pilot Study
Authors: Picca Andrew , Wahlquist Amy E. , Hudspeth Michelle
Published: October 2020

Adequate bone marrow recovery is a discharge requirement after admission for febrile neutropenia in oncology patients, without specific threshold in consensus guidelines. In January 2016, our institution implemented count recovery criteria of absolute neutrophil count ≥100 cells/μL and absolute phagocyte count ≥300 cells/μL compared with prior criteria of absolute neutrophil count ≥500 cells/μL. Retrospective analysis comparing pre (July 2013 to December 2015, N=68) and post (January 2016 to June 2018, N=30) groups showed no difference in readmissions (P>0.9), no patient deaths, and decreased average length of stay in the post group (P<0.0001). Updated count recovery criteria seem feasible and safe.
Exploring Cancer Treatment Experiences for Patients With Preexisting Mobility Disability
Authors: Agaronnik Nicole D. , El-Jawahri Areej , Kirschner Kristi , Iezzoni Lisa I.
Published: October 2020

Objective

We explored the process of cancer care for patients with preexisting mobility disability, focusing on treatment decisions and experiences.

Design

We recruited 20 participants with preexisting mobility disability, requiring use of an assistive device or assistance with activities of daily living, subsequently diagnosed with cancer (excluding skin cancers). We conducted open-ended individual interviews, which reached data saturation and were transcribed verbatim for conventional content analysis.

Results

Concerns coalesced around 4 themes: disability-related healthcare experiences affect cancer treatment decisions; concerns about cancer treatment worsening functional impairments; access barriers; and limited provider awareness and biases about treating people with disability. Residual fear from previous medical interventions and concerns about exacerbating functional impairments influenced cancer treatment preferences. Participants also raised concerns that their underlying disability may be used to justify less aggressive treatment. Nevertheless, cancer treatment did exacerbate mobility difficulties for some participants. Inaccessible hospital rooms, lack of accessible medical equipment, and attitudinal barriers complicated treatments.

Conclusions

People with preexisting mobility disability experience barriers to cancer treatment, compromising quality of care and potentially outcomes. Further training and proactive planning for accommodating disability during cancer treatment and rehabilitation are warranted.

To Claim CME Credits

Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME

CME Objectives

Upon completion of the article, the reader should be able to: (1) Recognize inadequate accommodations that compromise the diagnosis and treatment of a new cancer in patients with preexisting disability; (2) Recommend involving rehabilitation specialists in the process of care and clinical decision making from the time of cancer diagnosis for patients with preexisting disability newly diagnosed with malignancy; and (3) In the setting of accessibility barriers, facilitate efforts to accommodate patients with preexisting disability to improve quality of care in diagnosing and treating cancer.

Level

Advanced

Accreditation

The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Reduced Heart Rate Variability in Patients With Medically Unexplained Physical Symptoms: A Meta-Analysis of HF-HRV and RMSSD
Authors: Vreijling Sarah R. , Troudart Yael , Brosschot Jos F.
Published: October 2020

Objective

Medically unexplained physical symptoms (MUPS) and related syndromes are common and place a substantial burden on both patients and society. Chronic psychological distress and dysregulation of the autonomic nervous system may be common factors associated with MUPS, although previous studies have reported mixed results. The aims of this meta-analysis are to provide an updated synthesis of studies investigating heart rate variability (HRV) indices associated with autonomic nervous system functioning in three common MUPS syndromes and to explain inconsistencies in previous study findings.

Methods

Literature search yielded 58 studies comparing HRV indices of reduced parasympathetic activity of healthy individuals with those of patients with chronic fatigue syndrome (n
patients = 271), irritable bowel syndrome (n
patients = 1005), and fibromyalgia (n
patients = 534). Separate random-effects meta-analyses were conducted on studies measuring root mean square of successive differences (RMSSD) and high-frequency HRV (HF-HRV).

Results

Regardless of syndrome type, patients had significantly lower RMSSD (k = 22, Hedges g = −0.37 [−0.53 to −0.21], p < .001) and HF-HRV (k = 52, Hedges g = −0.69 [−1.03 to −0.36], p < .001) than did healthy individuals. Sample age and publication year explained a substantial variation in RMSSD, whereas controlling for confounders in statistical analyses explained variation in HF-HRV.

Conclusions

Lower RMSSD and HF-HRV in patients with MUPS versus healthy controls indicates that autonomic nervous system dysregulation, particularly lower parasympathetic activity, may play a role in patients with these conditions. This conclusion may have important implications for the underlying mechanisms and treatment of MUPS and related syndromes.
Implicit Affect, Heart Rate Variability, and the Metabolic Syndrome
Authors: Gouin Jean-Philippe , Thayer Julian F. , Deschênes Sonya S. , MacNeil Sasha , Booij Linda
Published: October 2020

Objective

Greater negative affect has been associated with an increased risk of the metabolic syndrome (METs). However, all studies to date have examined this association using explicit affect measures based on subjective ratings of emotional experiences. Prior studies suggest that implicit affect, representing the automatic, prereflective appraisal process involved in conscious emotional experiences, is associated with physiological stress responses independent of explicit affect. Furthermore, low resting heart rate variability (HRV) may increase the risk of stress-related diseases. The goals of this study were to evaluate the associations between implicit and explicit affect and METs and to assess whether these associations were amplified by lower HRV.

Methods

This secondary analysis of a larger study included 217 middle-aged women who completed measures of implicit affect, explicit affect, high-frequency HRV, and the different components of METs.

Results

There was a significant interaction between implicit negative affect and HRV predicting METs (odds ratio = 0.57, 95% confidence interval = 0.35–0.92), such that the combination of higher implicit affect and lower HRV was associated with a greater likelihood of METs. Similarly, there was a main effect of implicit negative affect as well as an interaction between implicit negative affect and HRV on the lipid accumulation product (b (standard error) = −0.06 (0.02), 95% confidence interval = −0.11 to −0.02), a combination of waist circumference and triglycerides.

Conclusions

Higher implicit negative affect in the context of lower HRV may be related to a greater risk of METs. The present findings highlight the relevance of including implicit affect measures in psychosomatic medicine research.
Preparing and Promoting Women for Leadership Positions in Radiology and the Imaging Industry
Authors: Rofsky Neil M. , Meltzer Carolyn , Chertoff Jocelyn D. , Gilbreath Rachel , Canon Cheri L.
Published: October 2020

A dearth of women leaders in the field of radiology and affiliated industries persists despite a recognition of the importance, value, and impact that would derive from its rectification. A targeted educational collaboration, described herein, was established between academia and industry to address this deficit and to facilitate the placement of highly qualified women into leadership positions. The actionable platform offered has the potential to narrow the gap for underrepresented groups in professional leadership positions.
Atypical Large Vessel Vasculitis Presenting With Cholestatic Liver Abnormalities
Authors: Sangha Sameet , Lenert Aleksander , Dawoud Salma , Kaur Aneet , Yazan Hasan , Voigt Michael D. , Lenert Petar
Published: October 2020

Clinicians usually easily recognize cranial manifestations of giant cell arteritis (GCA) such as new-onset headache, jaw claudication, scalp tenderness, and abrupt changes in visual acuity or blindness; however, when presented with an aberrant clinical course, the diagnosis becomes more elusive. In addition to temporal arteries and other extracranial branches of the carotid arteries, large vessel vasculitis (LVV) can also affect other blood vessels including coronary arteries, aorta with its major branches, intracranial blood vessels, and hepatic arteries.

Over time, the scope of the symptoms typically associated with LVV has broadened and includes cases of fever of unknown origin accompanied with other constitutional symptoms that can mimic a range of neoplastic and infectious diseases. In up to half of patients with atypical LVV, liver enzyme level elevations with a cholestatic pattern have been observed. Alkaline phosphatase level and γ-glutamyl transferase level elevations tend to be more prevalent in those LVV patients with vigorous inflammatory responses, particularly in those with fever and other nonspecific constitutional symptoms. These patients also have more profound anemia and thrombocytosis. With the exception of rare instances of vasculitides and granulomas affecting the liver tissue, liver biopsy is generally of little help and primarily shows nonspecific changes of fatty liver.

In this article, we review 3 patients who were eventually diagnosed with atypical LVV. The diagnosis was confirmed with temporal artery biopsy in 2 patients and with positron emission tomography/computed tomography in 1 patient. The common hepatic abnormality observed in all patients was the elevation of alkaline phosphatase level, which tended to respond rapidly to initiation of immunosuppressive treatment.
Dual PET Imaging of an H3K27M-Mutant Glioma With 18F-GE-180 and 18F-FET PET
Authors: Vettermann Franziska J. , Unterrainer Marcus , Ruf Viktoria , Fleischmann Daniel F. , Rupprecht Rainer , Forbrig Robert , Herms Jochen , Tonn Joerg C. , Belka Claus , Bartenstein Peter , Niyazi Maximilian , Albert Nathalie L.
Published: October 2020

A 25-year-old man presented with headache and intracranial pressure symptoms. On MRI, an intracranial lesion was detected in the right thalamus with exophytic growth into the third ventricle and inhomogeneous contrast enhancement without necrosis. Dual amino acid (18F-FET) and TSPO (18F-GE-180) PET imaging showed high tumor-to-background ratios in both scans and a short time-to-peak in 18F-FET uptake dynamics. Biopsy revealed a diffuse midline glioma, H3K27M-mutant (WHO grade IV), a novel entity in the 2016 WHO classification with poor clinical outcome. Our case shows that the highly aggressive features of this tumor entity can be visualized in vivo by both PET modalities.
A Peptide-Based Checkpoint Immunomodulator Alleviates Immune Dysfunction in Murine Polymicrobial Sepsis
Authors: Phares Timothy W. , Kotraiah Vinayaka , Chung Chun-Shiang , Unsinger Jacqueline , Mazer Monty , Remy Kenneth E. , Browne Cecille D. , Buontempo Peter , Mansour Marc , Pannucci James , Ayala Alfred , Hotchkiss Richard S. , Gutierrez Gabriel M.
Published: October 2020

Sepsis-induced immunosuppression involves both innate and adaptive immunity and is associated with the increased expression of checkpoint inhibitors, such as programmed cell-death protein 1 (PD-1). The expression of PD-1 is associated with poor outcomes in septic patients, and in models of sepsis, blocking PD-1 or its ligands with antibodies increased survival and alleviated immune suppression. While inhibitory antibodies are effective, they can lead to immune-related adverse events (irAEs), in part due to continual blockade of the PD-1 pathway, resulting in hyperactivation of the immune response. Peptide-based therapeutics are an alternative drug modality that provide a rapid pharmacokinetic profile, reducing the incidence of precipitating irAEs. We recently reported that the potent, peptide-based PD-1 checkpoint antagonist, LD01, improves T-cell responses. The goal of the current study was to determine whether LD01 treatment improved survival, bacterial clearance, and host immunity in the cecal-ligation and puncture (CLP)-induced murine polymicrobial sepsis model. LD01 treatment of CLP-induced sepsis significantly enhanced survival and decreased bacterial burden. Altered survival was associated with improved macrophage phagocytic activity and T-cell production of interferon-γ. Further, myeloperoxidase levels and esterase-positive cells were significantly reduced in LD01-treated mice. Taken together, these data establish that LD01 modulates host immunity and is a viable therapeutic candidate for alleviating immunosuppression that characterizes sepsis and other infectious diseases.
Neoadjuvant S-1 With Concurrent Radiotherapy Followed by Surgery for Borderline Resectable Pancreatic Cancer
Authors: Takahashi Shinichiro , Ohno Izumi , Ikeda Masafumi , Konishi Masaru , Kobayashi Tatsushi , Akimoto Tetsuo , Kojima Motohiro , Morinaga Soichiro , Toyama Hirochika , Shimizu Yasuhiro , Miyamoto Atsushi , Tomikawa Moriaki , Takakura Norihisa , Takayama Wataru , Hirano Satoshi , Otsubo Takehito , Nagino Masato , Kimura Wataru , Sugimachi Keishi , Uesaka Katsuhiko
Published: October 2020

Objective:

This study assessed whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate in BRPC.

Summary of Background Data:

Although a multidisciplinary approach that includes neoadjuvant treatment has been shown to be a better strategy for BRPC than upfront resection, a standard treatment for BRPC has not been established.

Methods:

A multicenter, single-arm, phase II study was performed. Patients who fulfilled the criteria for BRPC received S-1 (40 mg/m2bid) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery. The primary endpoint was the R0 resection rate. At least 40 patients were required, with a 1-sidedα= 0.05 andβ= 0.05 and expected and threshold values for the primary endpoint of 30% and 10%, respectively.

Results:

Fifty-two patients were eligible, and 41 were confirmed to have definitive BRPC by a central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade 3/4 toxicity with CRT was 43%. The R0 resection rate was 52% among the 52 eligible patients and 63% among the 41 patients who were centrally confirmed to have BRPC. Postoperative grade III/IV adverse events according to the Clavien-Dindo classification were observed in 7.5%. Among the 41 centrally confirmed BRPC patients, the 2-year overall survival rate and median overall survival duration were 58% and 30.8 months, respectively.

Conclusions:

S-1 and concurrent radiotherapy seem to be feasible and effective at increasing the R0 resection rate and improving survival in patients with BRPC.

Trial Registration:

UMIN000009172
Comparison of methods for the microbiological diagnosis of totally implantable venous access port-related infections
Authors: Kaya Esingül , Tollapi Lara , Pastore Alberto , Aringhieri Giacomo , Maisetta Giuseppantonio , Barnini Simona , Paolicchi Adriana , Batoni Giovanna , Esin Semih
Published: October 2020

Introduction. Totally implanted venous access ports (TIVAPs) are widely used in patients receiving long-term chemotherapy but may lead to serious complications such as catheter-related bloodstream infections (CRBSIs). Diagnosis of CRBSI requires catheter culture, but there is no consensus on microbiological culture methods to be adopted.

Aim. To compare three different procedures to recover bacterial cells from colonized catheters and to determine which section of the TIVAP (i.e. tip, septum, reservoir) is the probable source of infection. To investigate the correlation between blood culture results and TIVAP culture in order to get further evidence about the utility of differential time to positivity (DTP) as a diagnostic tool before TIVAP removal.

Hypothesis/Gap statement. Comparisons of different diagnostic procedures for catheter culture have been rarely reported for TIVAPs. We hypothesized that the optimization of methods to recover micro-organisms from different parts of TIVAPs may help to decrease the number of false-negative results in the diagnosis of TIVAP-related bloodstream infections.

Methodology. A total of 53 TIVAPs removed because of suspected infection (n=36) or end of use (n=17) were evaluated. The reservoir, the septum and the catheter tip were separated and subjected to different treatments for the recovery of adherent micro-organisms: (a) flushing of the catheter lumen, (b) sonication and flushing, (c) treatment with dithiothreitol and flushing. The three methods were also evaluated in an in vitro catheter infection model with

Staphylococcus epidermidis

. Culture results were compared to those obtained from paired blood cultures drawn from TIVAP and peripheral vein and to the relative DTP.

Results. The results obtained demonstrated that vigorous flushing/vortexing of the catheter lumen/septum, allows the recovery of a number of micro-organisms comparable to that of more complex procedures such as sonication or chemical treatment. Among 24 positive TIVAP-cultures, nine were tip-culture negative, whereas the corresponding reservoirs and septa were culture positive. A good correlation was observed between DTP and TIVAP cultures (P<0.001).

Conclusions. The results support the evidence that sending the port reservoir in addition to the catheter tip to the microbiology laboratory may increase the sensitivity and the accuracy of CRBSI diagnosis. Moreover, when a TIVAP-related infection is suspected, DTP is a useful diagnostic tool to decide between device removal or a more conservative approach.
R-type bacteriocins of Xenorhabdus bovienii determine the outcome of interspecies competition in a natural host environment
Authors: Thappeta Kishore Reddy Venkata , Ciezki Kristin , Morales-Soto Nydia , Wesener Shane , Goodrich-Blair Heidi , Stock S. Patricia , Forst Steven
Published: October 2020

Xenorhabdus

species are bacterial symbionts of Steinernema nematodes and pathogens of susceptible insects. Different species of Steinernema nematodes carrying specific species of

Xenorhabdus

can invade the same insect, thereby setting up competition for nutrients within the insect environment. While

Xenorhabdus

species produce both diverse antibiotic compounds and prophage-derived R-type bacteriocins (xenorhabdicins), the functions of these molecules during competition in a host are not well understood.

Xenorhabdus bovienii

(Xb-Sj), the symbiont of Steinernema jollieti, possesses a remnant P2-like phage tail cluster, xbp1, that encodes genes for xenorhabdicin production. We show that inactivation of either tail sheath (xbpS1) or tail fibre (xbpH1) genes eliminated xenorhabdicin production. Preparations of Xb-Sj xenorhabdicin displayed a narrow spectrum of activity towards other

Xenorhabdus

and

Photorhabdus

species. One species,

Xenorhabdus szentirmaii

(Xsz-Sr), was highly sensitive to Xb-Sj xenorhabdicin but did not produce xenorhabdicin that was active against Xb-Sj. Instead, Xsz-Sr produced high-level antibiotic activity against Xb-Sj when grown in complex medium and lower levels when grown in defined medium (Grace’s medium). Conversely, Xb-Sj did not produce detectable levels of antibiotic activity against Xsz-Sr. To study the relative contributions of Xb-Sj xenorhabdicin and Xsz-Sr antibiotics in interspecies competition in which the respective

Xenorhabdus

species produce antagonistic activities against each other, we co-inoculated cultures with both

Xenorhabdus

species. In both types of media Xsz-Sr outcompeted Xb-Sj, suggesting that antibiotics produced by Xsz-Sr determined the outcome of the competition. In contrast, Xb-Sj outcompeted Xsz-Sr in competitions performed by co-injection in the insect Manduca sexta, while in competition with the xenorhabdicin-deficient strain (Xb-Sj:S1), Xsz-Sr was dominant. Thus, xenorhabdicin was required for Xb-Sj to outcompete Xsz-Sr in a natural host environment. These results highlight the importance of studying the role of antagonistic compounds under natural biological conditions.
sMAdCAM:IL-6 ratio influences disease progression and anti-viral responses in SARS-CoV-2 infection
Authors: Jagtap Dhanashree , Bhor Vikrant M , Bhowmick Shilpa , Kasarpalkar Nandini , Sagvekar Pooja , Kulkarni Bhalchandra , Pathak Manish , Chatterjee Nirjhar , Dolas Pranam , Palav Harsha , Kaginkar Snehal , Bhagat Sharad , Munshi Itti , Parikh Swapneil , Agrawal Sachee , Pawar Chandrakant , Kaneria Mala , Mahale Smita D , Shastri Jayanthi , Patel Vainav
Published: October 2020

Recent studies positing the gut as a sanctuary site for viral persistence in SARS-CoV-2 infection highlight the importance of assimilating profiles of systemic as well as gut inflammatory mediators to understand the pathology of COVID-19. Also, the role of these markers in governing virus specific immunity following infection remains largely unexplored. A cohort (n=84) of SARS-C0V-2 infected individuals included a group of in-patients (n=60) at various stages of disease progression together with convalescent individuals (n=24) recruited between April and June 2020 from Mumbai, India. Follow-up of 35 in-patients at day 7 post diagnosis was carried out. Th1/Th2/Th17 cytokines along with soluble MAdCAM (sMAdCAM) levels in plasma were measured. Also, anti-viral humoral response as measured by rapid antibody test (IgG, IgM), Chemiluminescent Immunoassay (IgG) and antibodies binding to SARS-CoV-2 proteins were measured by Surface Plasmon Resonance (SPR) from plasma.IL-6 and sMAdCAM levels among in-patients inversely correlated with one another. When expressed as a novel integrated marker –sMIL index (sMAdCAM/IL-6 ratio), these levels were incrementally and significantly higher in various disease states with convalescents exhibiting the highest values. Importantly, sMAdCAM levels as well as sMIL index (fold change) correlated with peak association rates of receptor binding domain and fold change in binding to spike respectively as measured by SPR. Our results highlight key systemic and gutassociated parameters that need to be monitored and investigated further to optimally guide therapeutic and prophylactic interventions for COVID-19.