bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of APC gene promoter methylation and the risk of gastric cancer
Authors: Zhou Xueliang , Jiao Dechao , Dou Mengmeng , Zhang Weijie , Hua Hao , Chen Jianjian , Li Zhaonan , Li Lifeng , Han Xinwei
Published: April 2020

Background:

The methylation status of the adenomatous polyposis coli (APC) promoter has been shown to be associated with the occurrence of gastric cancer, but this finding remains controversial. The aim of this study was to investigate the relationship between methylation of the APC gene promoter and gastric cancer.

Methods:

We searched the Web of Science, EMBASE, Medline, and Cochrane Central Register of Controlled Trials (CENTRAL) databases from the date of creation until August 1, 2019. According to the inclusion criteria, the relationship between the methylation status of the APC gene promoter and gastric cancer was investigated. The incidence of APC promoter methylation in the tissues or blood of patients with and without gastric cancer was compared. The results are expressed as the odds ratio (OR) and 95% confidence interval (CI). The pooled OR of each study was estimated using a fixed effects model or a random effects model to generate forest plots. We further validated the results using the MethHC database.

Results:

Eight studies (985 samples) were included. Our meta-analysis showed that the incidence of APC promoter methylation in patients with gastric cancer was higher than that of patients without gastric cancer (OR = 3.86, 95% CI 1.71–8.74, P = .001). Methylation of the APC promoter is associated with the incidence of gastric cancer, and it increases the risk of gastric cancer.

Conclusion:

This study provides a new strategic direction for research on gastric cancer. Methylation of the APC promoter may be a potential biomarker for the diagnosis of gastric cancer, but the results of this work require further confirmation.
Outcomes of patients with spinal metastases from renal cell carcinoma treated with conventionally-fractionated external beam radiation therapy
Authors: Lee Chia Ching , Tey Jeremy Chee Seong , Cheo Timothy , Lee Chau Hung , Wong Alvin , Kumar Naresh , Vellayappan Balamurugan
Published: April 2020

Renal cell carcinoma (RCC) has been traditionally thought to be radioresistant. This retrospective cohort study aims to assess the outcomes of patients with spinal metastases from RCC treated with conventionally-fractionated external beam radiation therapy (cEBRT) in our institution.

Patients diagnosed with histologically or radiologically-proven RCC who received palliative cEBRT to spinal metastases, using 3-dimensional conformal technique between 2009 and 2018 were reviewed. Local progression-free survival (PFS), overall survival (OS) and common terminology criteria for adverse events version 4.0-graded toxicity were assessed. Univariable and multivariable Cox proportional hazards regression analyses were performed to evaluate for predictors associated with survivals.

Thirty-five eligible patients with forty spinal segments were identified, with a median follow-up of 7 months (range, 0–47). The median equivalent dose in 2 Gy fractions (EQD2) was 32.5 Gy 10 (range, 12–39). Thirty-seven percent of patients underwent surgical intervention. At the time of last follow-up, all but 1 patient had died. Seven patients developed local progression, with the median time to local progression of 10.2 months. The median local PFS and OS were 3.3 and 4.8 months. There was no grade 3 or higher toxicity. A higher radiation dose (equivalent dose to 2 Gy fraction <32.5 Gy 10 vs ≥32.5Gy 10) (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.17–3.18; P-value (P) = .68) and spinal surgery (HR, 2.35; 95% CI, 0.53–10.29; P = .26) were not significantly associated with local PFS on univariable analysis. Multivariable analysis showed that higher Tokuhashi score (HR, 0.41; 95% CI, 0.19–0.88; P = .02), lower number of spinal segments irradiated (HR, 1.18; 95% CI, 1.01–1.37; P = .04) and use of targeted therapy (HR, 0.41; 95% CI, 0.18–0.96; P = .04) were independent predictors for improved OS.

For an unselected group of patients with RCC, there is no significant association between higher radiation dose and improved local control following cEBRT. This may be due to their short survivals. With the use of more effective systemic therapy, including targeted therapy and immunotherapy, survival will likely be prolonged. A tailored-approach is needed to identify patients with good prognosis who may still benefit from aggressive local treatments.
Surgical treatment of asymptomatic epithelioid hemangioendothelioma originating from the superior vena cava
Authors: Lee Seok Soo , Lee Jang Hoon
Published: April 2020

Rationale:

Epithelioid hemangioendothelioma is a rare endothelial tumor with a low-grade malignancy. This tumor can be treated with complete resection.

Patient concerns:

A 20-year-old Korean man visited our hospital due to an abnormal finding on standing chest PA X-ray. He did not have any past medical history.

Diagnosis:

Chest computed tomography shows a well-defined, oval-shaped tumor invading the brachiocephalic vein and superior vena cava. A malignant tumor of vascular origin was diagnosed by a percutaneous needle biopsy.

Interventions:

We performed en-bloc resection including the great vessels for complete resection of the tumor. Histologic evaluation confirmed the lesion to be a hemangioendothelioma and the surgical margins were free from tumor invasion.

Outcomes:

Fourteen days later, the patient was discharged without any complication. Thirty months after surgery, recurrences, or metastasis were not detected.

Lessons:

Epithelioid hemangioendothelioma is a rare malignant endothelial tumor in the central vein. Surgery is the treatment of choice and shows good results. We introduce and appropriate surgical method to ensure successful treatment for rare disease.
Postoperative Crohn's disease management
Authors: Barnes Edward L.
Published: April 2020

Purpose of review

Despite multiple advances in the medical treatment of Crohn's disease, it is recognized that a significant proportion of patients will ultimately require surgical resection at some point during their disease course. This review focuses on the postoperative management of patients with Crohn's disease, with the goal of preventing endoscopic and clinical recurrence, and future surgery.

Recent findings

Surgery is an integral part of the multidisciplinary approach to the management of patients with Crohn's disease. Recent literature and guidelines have focused on a standardized and evidence-based approach to the management of patients in the postoperative setting. This approach should utilize risk stratification at the time of surgery, initiation of appropriate therapy among high-risk patients, and objective evaluation in the postoperative period, including ileocolonoscopy at 6–12 months after a surgical resection.

A standardized approach to the postoperative management of patients with Crohn's disease is critical. Identifying those patients at high-risk for endoscopic and clinical recurrence is essential, as these patients will likely require early medical therapy. While novel objective assessments are emerging, all patients should undergo ileocolonoscopy at 6–12 months and further decision making should be based on the presence of endoscopic recurrence.
Heart transplantation in cardiac storage diseases: data on Fabry disease and cardiac amyloidosis
Authors: Di Nora Concetta , Livi Ugolino
Published: April 2020

Purpose of review

To deeply investigate one type of intracellular cardiac storage disease, the Fabry disease and one example of extracellular cardiac storage disease, the cardiac amyloidosis, with the aim to collect data about cardiac treatment at the end-stage level and the feasibility of heart transplantation (HTx) in this setting of patients.

Recent findings

Some registry describes that Fabry disease and cardiac amyloidosis showed similar characteristics as hypertrophic cardiomyopathies; thus, their correct diagnosis is often missing or time consuming. A multiorgan approach is mandatory to recognize the main systemic findings of these diseases, involving also the kidneys, the brain, the autonomous system and the skin.

The early diagnosis of these diseases is required to start as soon as possible the correct therapy for the patients affected. However, the end-stage heart failure is common and HTx could be offered to selected patients, especially if affected by light chain cardiac amyloidosis, to allow to perform the autologous stem cell transplantation after the cardiac transplant. Considering the Fabry disease patients, the enzyme recombinant therapy is also mandatory after HTx to avoid potential release of the systemic disease on the donor graft.
Current status of pediatric mechanical circulatory support
Authors: Spigel Zachary A. , Cho Junsang , Adachi Iki
Published: April 2020

Purpose of review

The field of pediatric mechanical circulatory support has experienced exponential evolution in recent decades. With favorable complication profiles, implantable continuous-flow ventricular assist devices (VADs) have become a standard option in children, as has been seen in the adult counterpart. Nevertheless, there still exists room for further advances, not just for survival, but throughout the whole trajectory of treatment courses. With reviewing the current state of pediatric VAD support, including existing challenges, we aim to highlight the targets clinicians should focus on for further improvement of pediatric VAD support.

Recent findings

The field of pediatric VAD has been steadily growing, as evidenced by an increasing number of total VAD implants, particularly with continuous-flow VAD. Currently, HeartWare HVAD (Medtronic Inc., Mounds View, MN) is the most widely used continuous-flow VAD in children with excellent performance. However, only half of the children with HVAD are discharged home, which is drastically different from adult patients, suggesting that the pediatric field is still in the process of maturation. Additionally, outcomes of VAD support for complex congenital heart defect, particularly single ventricle physiology, remain suboptimal, despite an increasing number of such patients.

With the ongoing advancement, the field of pediatric VAD support is undergoing a rapid maturation process. This will eventually lead to further paradigm changes, including the use of VAD as permanent therapy.
Redefining marginality: donor lung criteria
Authors: Kukreja Jasleen , Chen Joy , Brzezinski Marek
Published: April 2020

Purpose of review

Despite an increase in lung transplantation globally, the waitlist mortality persists due to organ shortage. In order to keep up with the demand, the marginal lung donor criteria need to be revisited. The goal of this review is to redefine the lung donor criteria based on the most recent data.

Recent findings

Recent evidence indicates that lungs from donor with traditional extended criteria such as, age more than 55, PaO
2/FiO2 threshold of less than 300, ischemia time more than 6 h, positive sputum microbiology, abnormal radiography no longer represent contraindications to lung transplantation by themselves. In addition, the introduction of new antiviral agents, organs from Hepatitis C positive donors, though not extended in the traditional sense, have shown positive outcomes.

The decision to use such organs, including those with smoking history, should be taken in totality weighing both donor and recipient characteristics. Hence, authors would advocate removing the term ‘marginal’ or ‘extended’ from lung donor criteria.
Celiac Disease in Patients With Cystic Fibrosis on Ivacaftor
Authors: Hjelm Michelle , Shaikhkhalil Ala K.
Published: April 2020

Cystic fibrosis transmembrane conductance regulator (CFTR) protein modulators have revolutionized care for individuals with cystic fibrosis (CF) with positive effects on the gastrointestinal (GI) tract. There is emerging evidence linking CFTR dysfunction to celiac disease (CD). We present 3 cases of patients with CF, genotype F508del/G551D, treated with CFTR modulator, ivacaftor, and diagnosed with CD. These patients tested for CD because they had persistent GI symptoms that had partially improved with ivacaftor. This case series highlights the importance of a better understanding of how CFTR modulators impact the GI tract, their possible link to CD, and the importance of considering CD when evaluating GI symptoms in individuals with CF.
Mutations in Myosin 5B in Children With Early‐onset Cholestasis
Authors: Cockar Iram , Foskett Pierre , Strautnieks Sandra , Clinch Yasmin , Fustok Jana , Rahman Obydur , Sutton Harry , Mtegha Marumbo , Fessatou Smaragdi , Kontaki Elena , Papaevangelou Vassiliki , Deheragoda Maesha , Thompson Richard J. , Grammatikopoulos Tassos
Published: April 2020

Objectives:

Mutations in Myosin 5B (MYO5B) are known to be associated with microvillous inclusion disease (MVID) a genetic cause of neonatal intractable diarrhoea. More recently, they have been reported in children with cholestasis but without typical gastrointestinal symptoms of MVID. We describe our series of children with cholestasis and mutations in MYO5B.

Methods:

Clinical, laboratory, and histological data were collected from patients with cholestasis and pathogenic mutations in MYO5B, found by next generation sequencing (NGS) but with minimal gastrointestinal disease.

Results:

Six patients (3 boys) were identified. Median age at presentation was 19 months (range, 3–92). Presenting features were jaundice, pale stools, pruritus, and failure to thrive. Patients 5 and 6 had intractable diarrhoea until the age of 3 and 7 years, respectively, but currently are on full enteral diet with no intestinal symptoms. Median values for serum total bilirubin were 55 μmol/L (2–500), alanine aminotransferase 73I IU/L (32–114), γ‐glutamyltransferase 7 IU/L (7–10), and serum bile acids 134 μmol/L (18–274). Three patients underwent 1 or more types of biliary diversion for symptom control. Median follow‐up was 5 years (2–22). At most recent follow‐up, they all reported pruritus while on antipruritics. Patient 1 had a liver transplant.

Conclusions:

We identified 6 patients, with mutations in MYO5B, early‐onset cholestasis and pruritus, with variable response to biliary diversion without typical MVID.
Children with Attention-deficit/Hyperactivity Disorder Show an Altered Eye Movement Pattern during Reading
Authors: Molina Rubén , Redondo Beatriz , Vera Jesús , García José Antonio , Muñoz-Hoyos Antonio , Jiménez Raimundo
Published: April 2020

SIGNIFICANCE

Attention-deficit/hyperactivity disorder (ADHD) is characterized by oculomotor abnormalities. However, the eye movement pattern of children with ADHD during reading has yet to be fully determined. This investigation provides novel insights into the altered eye movement pattern during oral reading of nonmedicated children with pure ADHD in comparison with age-matched controls.

PURPOSE

The purpose of this study was to objectively compare the eye movement pattern during oral reading in a group of nonmedicated children with pure ADHD and an age-matched control group.

METHODS

Forty-one children, 21 children with pure ADHD (9.3 ± 2.2 years, 15 boys) and 20 control children (9.3 ± 2.5 years, 10 boys), orally read a standardized text according to their age while the eye movement pattern was objectively recorded using the Visagraph Eye Movement recording system.

RESULTS

The Bayesian statistical analyses revealed that children with ADHD exhibited a significantly higher number of fixations (Bayes factor 10 [BF10] = 3.39), regressions (BF10 = 9.97), saccades in return sweeps (BF10 = 4.63), and anomalies of fixations and regressions (BF10 = 3.66) compared with controls. In addition, children with ADHD significantly showed longer reading times (BF10 = 31.29), as well as lower reading rate (BF10 = 156.74) and grade-level equivalent (BF10 = 168.24) in comparison with controls.

CONCLUSIONS

Our data showed that the nonmedicated children with pure ADHD have an altered eye movement pattern during oral reading when compared with controls, which cannot be attributable to any comorbid condition. The present outcomes may help to understand the link between ADHD and reading performance and design the most pertinent strategies to enhance the reading skills of this population.
Comparison of Two Lighting Assessment Methods when Reading with Low Vision
Authors: Henry Rebecca , Duquette Josée , Wittich Walter
Published: April 2020

SIGNIFICANCE

Lighting assessments are an important component of low-vision rehabilitation but are rarely studied systematically. Our study indicates that preferred lighting levels support improvements in reading ease and enjoyment, independently of the evaluation technique. To determine preferred illumination level and color temperature, the LuxIQ is quicker to administer and covers broad options of settings.

PURPOSE

The purpose of this study was to determine if preferred lighting, as assessed by the LuxIQ versus a standard lighting assessment, leads to better reading outcomes in individuals with low vision.

METHODS

Preferred lighting was assessed at home with visually impaired persons (mean age, 75.3 years), using the LuxIQ (n = 18) or a standard technique based on trying out light bulbs of various intensity and color temperature (n = 16). Maximum reading speed and reading acuity were measured before the lighting intervention and then under the preferred lighting conditions. A 1-month telephone follow-up evaluated the (1) compliance with the lighting recommendations and, for those who modified their lighting, (2) their level of satisfaction with the length of reading time and eye strain felt during reading.

RESULTS

Compared with usual lighting conditions, most participants preferred a cooler temperature at a higher illuminance level. Neither lighting assessment type appeared to lead to substantially improved objectively measurable reading outcomes. At the 1-month follow-up, 56% of the participants had modified their lighting, having a significant effect on satisfaction (P < .01), independent of assessment method. Of 18 respondents, 16 (87.5%) mentioned that reading was more enjoyable or easier with the lighting modifications.

CONCLUSIONS

Both lighting assessment methods lead to comparable results, but the LuxIQ is easier and faster to use. More research is needed to determine whether the LuxIQ is suitable to be incorporated into clinical practice.
The Effects of Age, Distraction, and Simulated Central Vision Impairment on Hazard Detection in a Driving Simulator
Authors: Zhang Christine (Ting) , Bowers Alex R. , Savage Steven W.
Published: April 2020

SIGNIFICANCE

Despite similar levels of visual acuity and contrast sensitivity reductions, simulated central vision impairment increased response times to a much greater extent in older than in younger participants.

PURPOSE

Driving is crucial for maintaining independence in older age, but age-related vision impairments and in-vehicle auditory distractions may impair driving safety. We investigated the effects of age, simulated central vision impairment, and auditory distraction on detection of pedestrian hazards.

METHODS

Thirty-two normally sighted participants (16 younger and 16 older) completed four highway drives in a simulator and pressed the horn whenever they saw a pedestrian. Pedestrians ran toward the road on a collision course with the approaching vehicle. Simulated central vision impairment was achieved by attaching diffusing filters to a pair of laboratory goggles, which reduced visual acuity to 20/80 and contrast sensitivity by 0.35 log units. For drives with distraction, subjects listened to an audiobook and repeated out loud target words.

RESULTS

Simulated central vision impairment had a greater effect on reaction times (660-millisecond increase) than age (350-millisecond increase) and distraction (160-millisecond increase) and had a greater effect on older than younger subjects (828- and 492-millisecond increase, respectively). Simulated central vision impairment decreased safe response rates from 94.7 to 78.3%. Distraction did not, however, affect safety because older subjects drove more slowly when distracted (but did not drive more slowly with vision impairment), suggesting that they might have perceived greater threat from the auditory distraction than the vision impairment.

CONCLUSIONS

Older participants drove more slowly in response to auditory distraction. However, neither older nor younger participants adapted their speed in response to simulated vision impairment, resulting in unsafe detections. These results underline the importance of evaluating safety of responses to hazards as well as reaction times in a paradigm that flexibly allows participants to modify their driving behaviors.
Prevalence, Pathophysiology, Diagnostic Modalities, and Treatment Options for Dysphagia in Critically Ill Patients
Authors: Brodsky Martin B. , Nollet Joeke L. , Spronk Peter E. , González-Fernández Marlís
Published: April 2020

Postextubation dysphagia may impose a substantial burden on intensive care unit patients and healthcare systems. Approximately 517,000 patients survive mechanical ventilation during critical care annually. Reports of postextubation dysphagia prevalence are highly variable ranging between 3% and 93%. Of great concern is aspiration leading to the development of aspiration pneumonia when patients resume oral feeding. Screening for aspiration with a water swallow test has been reported to be positive for 12% of patients in the intensive care unit after extubation. This review aims to increase awareness of postextubation dysphagia and provide an updated overview of the current knowledge regarding prevalence, pathophysiology, diagnostic modalities, and treatment options.
Does Type of Sponsorship of Randomized Controlled Trials Influence Treatment Effect Size Estimates in Rehabilitation
Authors: Fuentes Jorge , Armijo-Olivo Susan , da Costa Bruno R. , Ha Christine , Saltaji Humam , Arenti Chiara , Negrini Stefano , Cummings Greta G.
Published: April 2020

Background

Sponsorship bias could affect research results to inform decision makers when using the results of these trials. The extent to which sponsorship bias affect results in the field of physical therapy has been unexplored in the literature. Therefore, the main aim of this study was to evaluate the influence of sponsorship bias on the treatment effects of randomized controlled trials in physical therapy area.

Methods

This was a meta-epidemiological study. A random sample of randomized controlled trials included in meta-analyses of physical therapy area were identified. Data extraction including assessments of appropriate influence of funders was conducted independently by two reviewers. To determine the association between biases related to sponsorship biases and effect sizes, a two-level analysis was conducted using a meta-meta-analytic approach.

Results

We analyzed 393 trials included in 43 meta-analyses. The most common sources of sponsorship for this sample of physical therapy trials were government (n = 205, 52%), followed by academic (n = 44, 11%) and industry (n = 39, 10%). The funding was not declared in a high percentage of the trials (n = 85, 22%). The influence of the trial sponsor was assessed as being appropriate in 246 trials (63%) and considered inappropriate/unclear in 147 (37%) of them. We have moderate evidence to say that trials with inappropriate/unclear influence of funders tended to have on average a larger effect size than those with appropriate influence of funding (effect size = 0.15; 95% confidence interval = −0.03 to 0.33).

Conclusions

Based on our sample of physical therapy trials, it seems that most of the trials are funded by either government and academia and a small percentage are funded by the industry. Treatment effect size estimates were on average 0.15 larger in trials with lack of appropriate influence of funders as compared with trials with appropriate influence of funding. Contrarily to other fields, industry funding was relatively small and their influence perhaps less marked. All these results could be explained by the relative youth of the field and/or the absence of clear industry interests. In front of the call for action by the World Health Organization to strengthen rehabilitation in health systems, these results raise the issue of the need of public funding in the field.
Feasibility of Short-Term PrEP Uptake for Men Who Have Sex With Men With Episodic Periods of Increased HIV Risk
Authors: Egan James E. , Ho Ken , Stall Ron , Drucker Moe T. , Tappin Ryan , Hendrix Craig W. , Marzinke Mark A. , Safren Steven A. , Mimiaga Matthew J. , Psaros Christina , Elsesser Steven , Mayer Kenneth H.
Published: April 2020

Background:

Pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate is efficacious in reducing HIV acquisition. For some gay, bisexual, and other men who have sex with men (MSM), daily ongoing PrEP may be unsuitable for use as a long-term prevention strategy because of episodic risk, cost issues, or concerns about the biological consequences of medication.

Setting:

This study evaluated the feasibility of short-term, fixed-interval episodic PrEP (Epi-PrEP) for use among vacationing MSM. We describe the feasibility of implementing a clinic-based Epi-PrEP pilot program for 48 MSM who reported occasional condomless sex and anticipated a defined high-risk time.

Methods:

This was a nonrandomized naturalistic study of an observational clinical intervention. The primary outcome assessed was adherence, as measured by self-report and plasma tenofovir levels.

Results:

Of 54 MSM who enrolled in the study, 48 completed the 3-month visit. The majority (93.7%) had tenofovir concentrations consistent with daily use on returning from vacation. Almost 3/4 reported condomless sex during vacation, and about 1/3 reported recreational drug use. During the 3-month follow-up, 1 participant had become HIV-infected because of a lapse in continued access to the PrEP after study. Although adverse events were common, none were serious. More than 70% of participants indicated an interest in daily ongoing PrEP use.

Conclusions:

Epi-PrEP was well tolerated by at risk MSM in this study, with high levels of medication adherence. Many participants felt the experience of initiating PrEP while on vacation could be a means for transition to long-term PrEP use.
Opioid analgesia: recent developments
Authors: Stein Christoph
Published: April 2020

Purpose of review

Opioids are potent drugs for the treatment of severe pain, but they are burdened by detrimental side-effects, such as respiratory depression, addiction, sedation and constipation. Their clinical application is undisputed in acute (e.g. perioperative) and cancer pain, but their use in chronic nonmalignant pain has met increasing scrutiny and has contributed to the opioid crisis. Thus, novel analgesics with reduced side-effects are badly needed.

Recent findings

Current research topics include enkephalinase inhibitors, allosteric and multivalent ligands, biased opioid receptor signaling and selective activation of peripheral opioid receptors in injured tissues.

Opioids still appear to be most promising among current approaches in the development of analgesics. Basic knowledge about pathophysiology of clinical pain and novel insights in pharmacology suggest that the most interesting perspectives are augmenting endogenous opioid actions and selectively targeting peripheral opioid receptors. The latter approach is additionally supported by evidence from clinical studies. Some biased, multivalent and peripherally selective agonists have advanced to phase III trials, but novel drugs have not become available for clinical application. Future strategies in analgesic drug development might include public–private partnerships and nonprofit pharmaceutical companies, as exemplified by the AIDS crisis and proposals to combat antibiotic resistance.
Language Sample Analysis With Bilingual Children
Authors: Ebert Kerry Danahy
Published: April 2020

Language sample analysis (LSA) has been called the “gold standard” for clinical language assessment with children learning more than one language. The research literature discussing this clinical tool with bilingual children has grown substantially in recent years. This article reviews and synthesizes the literature on LSA in order to provide guidance for clinicians seeking to utilize this tool with bilingual children. The focus is on oral narrative language samples, reflecting the currently available literature. The article reviews procedural considerations in eliciting and coding narratives with bilingual children and considers the evidence of effectiveness for different assessment purposes such as the identification of language disorders and the documentation of dual-language growth over time. Research findings are translated to clinical scenarios. Finally, gaps in the literature are identified.
Galectins in the brain: advances in neuroinflammation, neuroprotection and therapeutic opportunities
Authors: Barake Francisca , Soza Andrea , González Alfonso
Published: April 2020

Purpose of review

Galectin interactions with glycoproteins and glycolipids modulate a variety of cellular responses that are now increasingly explored to better understand neuroinflammation processes and eventually find new therapeutic opportunities for neurological diseases.

Recent findings

Gal-1 confirmed its indirect neuroprotective roles through anti-inflammatory properties whereas Gal-3 remains elusive, showing anti-inflammatory or pro-inflammatory roles depending on damaging conditions and genetic background of mice models. Interestingly, microglial intracellular rather than extracellular overexpression of Gal-3 arose as contributing to the pathogenesis of Huntington disease, involving NLRP3 inflammasome activation and inhibition of autophagic removal of damaged endolysosomes. Decreasing Gal-3 expression had favorable effects upon disease symptoms. Gal-3 expanded its role in this endolysosomal surveillance system originally involving Gal-8 and Gal-9, which protect cells against neuropathogenic proteins and becomes impaired or even detrimental under neurodegenerative conditions. Also, Gal-1, Gal-3 and Gal-4, together with changes in glycan structures define the outcome of neuroinflammation and remyelination processes. Gal-8 emerged as a new neuroprotector factor, which added to its immunosuppressive role and presence in human cerebrospinal fluid (CSF) may generate a neuroprotective environment in the brain.

Galectins modulate neuroinflammation and neurodegenerative processes contributing to microglia polarization, immunosurveillance and neuroprotection through extracellular and intracellular interactions with particular and dynamic patterns of glycans, suggesting potential therapeutic targets.
Advances in physical rehabilitation of multiple sclerosis
Authors: Centonze Diego , Leocani Letizia , Feys Peter
Published: April 2020

Purpose of review

Multiple sclerosis (MS) is a neurological disorder that heavily affects quality of life (QoL) and demands a multidisciplinary therapeutic approach. This includes multiple protocols and techniques of physical rehabilitation, ranging from conventional exercise paradigms to noninvasive brain stimulation (NIBS). Recently, studies showing the clinical efficacy of physical rehabilitation have remarkably increased, suggesting its disease-modifying potential.

Recent findings

Studies in animal models of MS have shown that physical exercise ameliorates the main disease pathological hallmarks, acting as a pro-myelinating and immunomodulatory therapy. NIBS techniques have been successfully applied to treat pain and urinary symptoms and lower limb function and spasticity, especially in combination with physical rehabilitation. Physical rehabilitation is reported to be well tolerated and effective in improving muscle function and fitness even in more disabled patients, and to enhance balance, walking and upper limb functional movements. Moreover, the dual motor--cognitive task performance can be improved by combined training protocols.

The literature here reviewed indicates the importance of clinical and preclinical research in addressing the impact of neurorehabilitation on MS disability, highlighting the need of further studies to reach a more comprehensive understanding of the mechanisms involved, the best combination of techniques and the proper timing of application.
Update on T cells in the virally infected brain: friends and foes
Authors: Ai Shenjian , Klein Robyn S.
Published: April 2020

Purpose of review

The present review will outline neuroprotective and neurotoxic effects of central nervous system (CNS) infiltrating T cells during viral infections. Evidence demonstrating differential roles for antiviral effector and resident memory T-cell subsets in virologic control and immunopathology in the CNS will be discussed. Potential therapeutic targets emanating from a growing understanding of T-cell-initiated neuropathology that impacts learning and memory will also be delineated.

Recent findings

The critical role for T cells in preventing and clearing CNS infections became incontrovertible during the era of acquired immunodeficiency syndrome. Recent studies have further defined differential roles of T-cell subsets, including resident memory T cells (Trm), in antiviral immunity and, unexpectedly, in postinfectious cognitive dysfunction. Mechanisms of T-cell-mediated effects include differential innate immune signaling within neural cells that are virus-specific.

T-cell cytokines that are essential for cell-mediated virologic control during neurotropic viral infections have recently been identified as potential targets to prevent post-infection memory disorders. Further identification of T-cell subsets, their antigen specificity, and postinfection localization of Trm will enhance the efficacy of immunotherapies through minimization of immunopathology.
“Leaky” and “Unstable” Neural Integrator Can Coexist—Paradox Observed in Multiple Sclerosis
Authors: Gupta Palak , Shaikh Aasef G.
Published: April 2020

The mechanism for stable gaze-holding requires a neural integrator that converts pulse of neural discharge to steady firing rate. The integrator is feedback-dependent, impaired feedback manifests as either “unstable” integration when it is too much or “leaky” when it is too little. The “unstable” integrator is known to cause sinusoidal oscillations of the eyes called pendular nystagmus, whereas the “leaky” integrator causes jerky eye oscillations called gaze-evoked nystagmus. We hypothesized that integrator can be simultaneously leaky and unstable. Mechanistically, some parts of network are served by increased feedback gain (unstable network), while other part would be decreased feedback gain (leaky). Both leaky and unstable, the network converges on the ocular motor plant, leading to simultaneously present gaze-evoked jerk and sinusoidal nystagmus. We tested our hypothesis by measuring eye movements with search coil technique in 7 multiple sclerosis patients. Five of these patients had gaze-evoked nystagmus and superimposed pendular nystagmus. The gaze-evoked nystagmus depicted all the features of “leaky” integrator, that is, the drifts were always toward the null that was located at the central eye-in-orbit orientation, there were no drifts at null, and the drift velocity increased as the eyes moved farther away from the null. The pendular nystagmus had all the features of “unstable” integrator, that is, constant 4- to 6-Hz frequency, eye-in-orbit position dependence of the oscillation amplitude, and the voluntary saccade causing an oscillatory phase reset. These features were then simulated in a computational model conceptualizing our hypothesis of simultaneously leaky and unstable neural integrator.
Central Venous Obstruction–Induced Intracranial Hypertension in Hemodialysis Patients: An Underrecognized Cause of Elevated Intracranial Pressure
Authors: Mackay Devin D. , Takacs Sara M.
Published: April 2020

Background:

Central venous obstruction (stenosis or occlusion) is common in patients with renal failure on hemodialysis and may be associated with intracranial hypertension (IH). Causes include vein injury from an endoluminal device, lumen obstruction from a device or thrombus, external vein compression, and high venous flow leading to vein intimal hyperplasia. A combination of high venous flow and central venous obstruction can lead to intracranial venous hypertension, impaired cerebrospinal fluid (CSF) resorption, and subsequent IH.

Evidence Acquisition:

We conducted a search of the English literature using the Ovid MEDLINE Database and PubMed, with a focus on reports involving IH and central venous obstruction in the setting of hemodialysis. We reviewed CSF flow dynamics, the risk factors and causes of central venous obstruction, and the evaluation, management, and outcomes of central venous obstruction-induced IH.

Results:

Twenty-four cases of IH related to central venous obstruction in hemodialysis patients were identified. Twenty patients had headaches (83.3%) and 9 had visual symptoms (37.5%). The brachiocephalic vein was the most common site of stenosis or occlusion (20/24, 83.3%). Twenty-one patients (87.5%) had resolution of IH with treatment. Two patients died from complications of IH (8.3%).

Conclusions:

Central venous obstruction–induced IH is likely underrecognized by clinicians and mimics idiopathic IH. Hemodialysis patients with IH should be screened with computed tomography venography of the chest. Optimal treatment is with vascular intervention or a CSF diversion procedure and can help prevent vision loss from papilledema or nervous system damage. Medical management may be appropriate in mild cases or as a bridge to definitive interventional treatment. Increased awareness among clinicians has potential to facilitate the timely diagnosis of this treatable condition with potential for good neurologic and visual outcomes.
Neurosarcoidosis Masquerading as Giant Cell Arteritis With Incidental Meningioma
Authors: Solyman Omar M. , Vizcaino Maria Adelita , Fu Roxana , Henderson Amanda D.
Published: April 2020

We present a case of vision loss secondary to neurosarcoidosis, which initially presented with severe bilateral vision loss, temporal headaches, and elevated erythrocyte sedimentation rate, concerning for giant cell arteritis. However, temporal artery biopsy was negative. Initial neuroimaging features were misinterpreted to represent a meningioma that did not account for his clinical presentation. Clinical course, including atypically rapid enlargement of presumed meningioma, development of skin lesions, appearance of optic nerve enhancement on MRI, and steroid response, strongly increased suspicion for sarcoidosis. Biopsy of a skin lesion demonstrated noncaseating granulomatous inflammation, consistent with sarcoidosis.
Phenotype of SARS-CoV-2-specific T-cells in COVID-19 patients with acute respiratory distress syndrome
Authors: Weiskopf Daniela , Schmitz Katharina S. , Raadsen Matthijs P. , Grifoni Alba , Okba Nisreen M.A. , Endeman Henrik , van den Akker Johannes P.C. , Molenkamp Richard , Koopmans Marion P.G. , van Gorp Eric C.M. , Haagmans Bart L. , de Swart Rik L. , Sette Alessandro , de Vries Rory D.
Published: April 2020

COVID-19 is associated with lymphopenia and ‘cytokine storm’, but no information is available on specific cellular immune responses to SARS-CoV-2. Here, we characterized SARS-CoV-2-specific CD4+ and CD8+ T-cells in patients with acute respiratory distress syndrome. The spike protein (S) proved a potent T-cell antigen and specific T-cells predominantly produced Th1 cytokines. These novel data are important in vaccine design and will facilitate evaluation of vaccine candidate immunogenicity.
International Electronic Health Record-Derived COVID-19 Clinical Course Profiles: The 4CE Consortium
Authors: Brat Gabriel A , Weber Griffin M , Gehlenborg Nils , Avillach Paul , Palmer Nathan P , Chiovato Luca , Cimino James , Waitman Lemuel R , Omenn Gilbert S , Malovini Alberto , Moore Jason H , Beaulieu-Jones Brett K , Tibollo Valentina , Murphy Shawn N , L’Yi Sehi , Keller Mark S , Bellazzi Riccardo , Hanauer David A , Serret-Larmande Arnaud , Gutierrez-Sacristan Alba , Holmes John J , Bell Douglas S , Mandl Kenneth D , Follett Robert W , Klann Jeffrey G , Murad Douglas A , Scudeller Luigia , Bucalo Mauro , Kirchoff Katie , Craig Jean , Obeid Jihad , Jouhet Vianney , Griffier Romain , Cossin Sebastien , Moal Bertrand , Patel Lav P , Bellasi Antonio , Prokosch Hans U , Kraska Detlef , Sliz Piotr , Tan Amelia LM , Ngiam Kee Yuan , Zambelli Alberto , Mowery Danielle L , Schiver Emily , Devkota Batsal , Bradford Robert L , Daniar Mohamad ,   APHP/Universities/INSERM COVID-19 research collaboration, Daniel Christel , Benoit Vincent , Bey Romain , Paris Nicolas , Serre Patricia , Orlova Nina , Dubiel Julien , Hilka Martin , Jannot Anne Sophie , Bréant Stéphane , Leblanc Judith , Griffon Nicolas , Burgun Anita , Bernaux Melodie , Sandrin Arnaud , Salamanca Elisa , Ganslandt Thomas , Gradinger Tobias , Champ Julien , Boeker Martin , Martel Patricia , Esteve Loic , Gramfort Alexandre , Grisel Olivier , Leprovost Damien , Moreau Thomas , Varoquaux Gael , Vie Jill-Jenn , Wassermann Demian , Mensch Arthur , Caucheteux Charlotte , Haverkamp Christian , Lemaitre Guillaume , Krantz Ian D. , Cormont Sylvie , South Andrew M ,   The Consortium for Clinical Characterization of COVID-19 by EHR (4CE), Cai Tianxi , Kohane Isaac S
Published: April 2020

We leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across 5 countries (www.covidclinical.net). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on comorbidities and temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions.
Comparative dynamic aerosol efficiencies of three emergent coronaviruses and the unusual persistence of SARS-CoV-2 in aerosol suspensions
Authors: Fears A.C. , Klimstra W.B. , Duprex P. , Hartman A. , Weaver S.C. , Plante K.C. , Mirchandani D. , Plante J.A. , Aguilar P.V. , Fernández D. , Nalca A. , Totura A. , Dyer D. , Kearney B. , Lackemeyer M. , Bohannon J.K. , Johnson R. , Garry R.F. , Reed D.S. , Roy C.J.
Published: April 2020

The emergent coronavirus, designated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a zoonotic pathogen that has demonstrated remarkable transmissibility in the human population and is the etiological agent of a current global pandemic called COVID-191. We measured the dynamic (short-term) aerosol efficiencies of SARS-CoV-2 and compared the efficiencies with two other emerging coronaviruses, SARS-CoV (emerged in 2002) and Middle Eastern respiratory syndrome CoV (MERS-CoV; emerged starting in 2012). We also quantified the long-term persistence of SARS-CoV-2 and its ability to maintain infectivity when suspended in aerosols for up to 16 hours.
Mesenchymal stromal cells for COVID-19: A living systematic review protocol
Authors: Rada Gabriel , Corbalán Javiera , Rojas Patricio ,   COVID-19 L·OVE Working Group
Published: April 2020

Objective

To determine the impact of mesenchymal stromal cells outcomes important to patients with COVID-19.

Design

This is the protocol of a living systematic review.

Data sources

We will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralised repository in L·OVE (Living OVerview of Evidence). L·OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L·OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal.

Eligibility criteria for selecting studies and methods

We adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question.

We will include randomised trials evaluating the effect of mesenchymal stromal cells versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating other coronavirus infections, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case we find no direct evidence from randomised trials, or if the direct evidence provides low- or very low-certainty for critical outcomes.

Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will pool the results using meta-analysis and will apply the GRADE system to assess the certainty of the evidence for each outcome.

A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it every time the conclusions change or whenever there are substantial updates.

Ethics and dissemination

No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.

PROSPERO Registration

Submitted to PROSPERO (awaiting ID allocation).
A Rapidly Deployable Negative Pressure Enclosure for Aerosol-Generating Medical Procedures
Authors: Chahal Anthony M. , Van Dewark Kenneth , Gooch Robert , Fukushima Erin , Hudson Zachary M.
Published: April 2020

Background

The coronavirus disease 2019 (COVID-19) pandemic presents significant safety challenges to healthcare professionals. In some jurisdictions, over 10% of confirmed cases of COVID-19 have been found among healthcare workers. Aerosol-generating medical procedures (AGMPs) may increase the risk of nosocomial transmission, exacerbated by present global shortages of personal protective equipment (PPE). Improved methods for mitigating risk during AGMPs are therefore urgently needed.

Methods

The Aerosol Containment Enclosure (ACE) was constructed from acrylic with silicone gaskets for arm port seals and completed with a thin plastic sheet. Hospital wall suction generated negative pressure within the ACE. To evaluate protective capability, differential pressures were recorded under static conditions and during simulated AGMPs. Smoke flow patterns, fluorescence aerosolization, and sodium saccharin aerosolization tests were also conducted.

Results

Negative pressures of up to -47.7 mmH2O were obtained using the enclosure with two wall suction units (combined outflow of 70 L min-1), with inflow of O2 of 15 L min-1. Negative pressures between -10 and - 35 mmH2O were maintained during simulated AGMPs, including oxygen delivery by mask, airway suctioning, bag-mask manual ventilation and endotracheal intubation of a potential COVID-19 patient. The ACE effectively contained smoke, fluorescein aerosol, and sodium saccharin aerosol within the enclosure during use.

Conclusions

The ACE is capable of maintaining negative pressure during simulated AGMPs. In all cases, containment was improved relative to an identical enclosure with non-occluded ports at ambient pressure. During the current COVID-19 pandemic, the use of such a device may assist in reducing nosocomial infections among healthcare providers.