Publications by authors named "David A Williams"

470 Publications

Mechanisms underlying genetic susceptibility to multisystem inflammatory syndrome in children (MIS-C).

J Allergy Clin Immunol 2021 Jul 2. Epub 2021 Jul 2.

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a pediatric complication of severe acute respiratory syndrome coronavirus 2 infection that is characterized by multiorgan inflammation and frequently by cardiovascular dysfunction. It occurs predominantly in otherwise healthy children. We previously reported haploinsufficiency of suppressor of cytokine signaling 1 (SOCS1), a negative regulator of type I and II interferons, as a genetic risk factor for MIS-C.

Objectives: We aimed to identify additional genetic mechanisms underlying susceptibility to severe acute respiratory syndrome coronavirus 2-associated MIS-C.

Methods: In a single-center, prospective cohort study, whole exome sequencing was performed on patients with MIS-C. The impact of candidate variants was tested by using patients' PBMCs obtained at least 7 months after recovery.

Results: We enrolled 18 patients with MIS-C (median age = 8 years; interquartile range = 5-12.25 years), of whom 89% had no conditions other than obesity. In 2 boys with no significant infection history, we identified and validated hemizygous deleterious defects in XIAP, encoding X-linked inhibitor of apoptosis, and CYBB, encoding cytochrome b-245, beta subunit. Including the previously reported SOCS1 haploinsufficiency, a genetic diagnosis was identified in 3 of 18 patients (17%). In contrast to patients with mild COVID-19, patients with defects in SOCS1, XIAP, or CYBB exhibit an inflammatory immune cell transcriptome with enrichment of differentially expressed genes in pathways downstream of IL-18, oncostatin M, and nuclear factor κB, even after recovery.

Conclusions: Although inflammatory disorders are rare in the general population, our cohort of patients with MIS-C was enriched for monogenic susceptibility to inflammation. Our results support the use of next-generation sequencing in previously healthy children who develop MIS-C.
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http://dx.doi.org/10.1016/j.jaci.2021.06.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252701PMC
July 2021

Cannabidiol Product Dosing and Decision-Making in a National Survey of Individuals with Fibromyalgia.

J Pain 2021 Jun 30. Epub 2021 Jun 30.

Anesthesiology Department, University of Michigan Medical School, Ann Arbor, Michigan.

Many people with fibromyalgia use cannabidiol (CBD) products despite limited rigorous evidence of benefit. In the current study, we conducted a secondary analysis of a cross-sectional survey of N = 878 people with fibromyalgia to investigate naturalistic decision making around CBD product choices, use patterns, and dosing. We subgrouped participants based on use of high-THC cannabis (HTC) in the past year (yes/no) as previous studies have shown that HTC use influences CBD use patterns. The study population was largely female (93.6%), white (91.5%) and 55.5 years old on average. Participants typically purchased CBD products online or at dispensaries, with purchasing driven by personal research (63%) rather than endorsement from medical professionals (16%). Overall, tinctures and topicals were the most common administration routes endorsed. However, participants in the past-year HTC group used inhalation routes far more frequently than those who did not (39.8% vs 7.1%). Among participants using CBD tinctures or edibles, the average dose per session was 16 mg and 24 to 27 mg per day, although approximately one-third of participants did not know what dose of CBD they used. Participants using both inhalation and non-inhalation administration routes reported greater symptom relief than those using non-inhalation routes alone. However, there was no consistent relationship between CBD dose and reported effects, possibly due to expectancy effects around CBD products or interindividual variability. Our granular investigation reveals variability of CBD product dosing practices for fibromyalgia, and how past-year HTC use influences CBD product use. Future clinical trials should investigate the potential benefits of low-dose (<50mg) botanical CBD products. Perspective: This article shows that past-year HTC use strongly influences how people with fibromyalgia choose and use CBD products. Participants typically used <50 mg/d of CBD, and there was no relationship between higher CBD dose and reported therapeutic benefit. Future clinical trials should investigate therapeutic benefits of low dose CBD.
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http://dx.doi.org/10.1016/j.jpain.2021.06.007DOI Listing
June 2021

Substituting Cannabidiol for Opioids and Pain Medications Among Individuals With Fibromyalgia: A Large Online Survey.

J Pain 2021 May 13. Epub 2021 May 13.

University of Michigan Medical School, Ann Arbor, Michigan.

People report substituting cannabis for pain medications, but whether cannabidiol (CBD) is used similarly remains unknown. CBD products can be CBD alone (isolate), hemp extract (containing <0.3% Δ-9-tetrahydrocannabinol [THC], other cannabinoids, and terpenes), or CBD-cannabis (containing >0.3% THC). In a secondary analysis from a cross-sectional survey, we examined substitution patterns among n = 878 individuals with fibromyalgia who currently used CBD. We sub-grouped participants by most commonly used CBD product (CBD isolate, hemp, CBD-cannabis, no preference) and whether they substituted CBD for medications. We investigated rationale for substituting, substitution-driven medication changes, CBD use patterns, and changes in pain-related symptoms (eg, sleep, anxiety). The study population was 93.6% female and 91.5% Caucasian, with an average age of 55.5 years. The majority (n = 632, 72.0%) reported substituting CBD products for medications, most commonly NSAIDs (59.0%), opioids (53.3%), gabapentanoids (35.0%), and benzodiazepines (23.1%). Most substituting participants reported decreasing or stopping use of these pain medications. The most common reasons for substitution were fewer side effects and better symptom management. Age, hemp products, past-year use of marijuana, and higher somatic burden were all associated with substituting (P's ≤ .05). Those who substituted reported larger improvements in health and pain than those who did not. Participants using CBD-cannabis reported significantly more substitutions than any other group (P's ≤ .001) and larger improvements in health, pain, memory, and sleep than other subgroups. This widespread naturalistic substitution for pain medications suggests the need for more rigorous study designs to examine this effect. PERSPECTIVE: This article shows that people with fibromyalgia are deliberately substituting CBD products for conventional pain medications despite the dearth of evidence suggesting CBD products may be helpful for fibromyalgia. CBD's medication-sparing and therapeutic potential should be examined in more rigorous study designs.
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http://dx.doi.org/10.1016/j.jpain.2021.04.011DOI Listing
May 2021

One dog's waste is another dog's wealth: A pilot study of fecal microbiota transplantation in dogs with acute hemorrhagic diarrhea syndrome.

PLoS One 2021 19;16(4):e0250344. Epub 2021 Apr 19.

Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa.

Canine acute hemorrhagic diarrhea syndrome (AHDS) has been associated in some studies with Clostridioides perfringens overgrowth and toxin-mediated necrosis of the intestinal mucosa. We aimed to determine the effect of a single fecal microbiota transplantation (FMT) on clinical scores and fecal microbiomes of 1 and 7 dogs with AHDS from New Zealand and South Africa. We hypothesized that FMT would improve AHDS clinical scores and increase microbiota alpha-diversity and short-chain fatty acid (SCFA)-producing microbial communities' abundances in dogs with AHDS after FMT. We sequenced the V3-V4 region of the 16S-rRNA gene in the feces of AHDS FMT-recipients and sham-treated control dogs, and their healthy donors at admission, discharge, and 30 days post-discharge. There were no significant differences in median AHDS clinical scores between FMT-recipients and sham-treated controls at admission or discharge (P = 0.22, P = 0.41). At admission, the Shannon diversity index (SDI) was lower in AHDS dogs than healthy donors (P = 0.002). The SDI did not change from admission to 30 days in sham-treated dogs yet increased in FMT-recipients from admission to discharge (P = 0.04) to levels not different than donors (P = 0.33) but significantly higher than sham-treated controls (P = 0.002). At 30 days, the SDI did not differ between FMT recipients, sham-treated controls, and donors (P = 0.88). Principal coordinate analysis of the Bray-Curtis index separated post-FMT and donor dogs from pre-FMT and sham-treated dogs (P = 0.009) because of increased SCFA-producing genera's abundances after FMT. A single co-abundance subnetwork contained many of the same OTUs found to be differentially abundant in FMT-recipients, and the abundance of this module was increased in FMT-recipients at discharge and 30 days, compared to sham-treated controls. We conclude in this small pilot study FMT did not have any clinical benefit. A single FMT procedure has the potential to increase bacterial communities of SCFA-producing genera important for intestinal health up to 30 days post-FMT.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250344PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055013PMC
April 2021

Electronic Delivery of Pain Education for Chronic Overlapping Pain Conditions: A Prospective Cohort Study.

Pain Med 2021 Jan 27. Epub 2021 Jan 27.

Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan, USA.

Objective: To examine the impact of educational materials for chronic overlapping pain conditions (COPCs), the feasibility of delivering materials online, and to explore its impact on self-reported self-management applications at 3-month follow-up.

Design: Prospective cohort study.

Setting: Online.

Subjects: Individuals from a university-wide active research repository with ≥1 coded diagnostic COPC by ICD-9/10 in the medical record.

Methods: We determined the number of COPCs per participant as indicated by diagnostic codes in the medical record. Consenting participants completed self-report questionnaires and read educational materials. We assessed content awareness and knowledge pre- and post-exposure to education. Comprehension was assessed via embedded questions in reading materials in real time. Participants then completed assessments regarding concept retention, self-management engagement, and pain-related symptoms at 3-months.

Results: N = 216 individuals enrolled, with 181 (84%) completing both timepoints. Results indicated that participants understood materials. Knowledge and understanding of COPCs increased significantly after education and was retained at 3-months. Patient characteristics suggested the number of diagnosed COPCs was inversely related to age. Symptoms or self-management application did not change significantly over the 3-month period.

Conclusions: The educational materials facilitated teaching of key pain concepts in self-management programs, which translated easily into an electronic format. Education alone may not elicit self-management engagement or symptom reduction in this population; however, conclusions are limited by the study's uncontrolled design. Education is likely an important and meaningful first step in comprehensive COPC self-management.
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http://dx.doi.org/10.1093/pm/pnab018DOI Listing
January 2021

Restored macrophage function ameliorates disease pathophysiology in a mouse model for IL10 receptor deficient very early onset inflammatory bowel disease.

J Crohns Colitis 2021 Feb 17. Epub 2021 Feb 17.

Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Background And Aims: Mutations in IL10 or the IL10-receptor lead to very early onset (VEO) inflammatory bowel disease (IBD), a life-threatening disease which is often unresponsive to conventional medication. Recent studies have demonstrated that defective IL-10 receptor signaling in innate immune cells is a key driver of severe intestinal inflammation in VEO-IBD. Specifically, IL10 unresponsiveness of macrophages, which govern the tight balance between pro- and anti-inflammatory responses in the intestinal system, plays a central role in the events leading to excessive inflammatory responses and the development of IBD.

Methods And Results: We here evaluated hematopoietic stem cell gene therapy in a VEO-IBD mouse model and demonstrate that the therapeutic response closely correlates with gene correction of the IL-10 signaling pathway in intestinal macrophages. This finding prompted us to evaluate the therapeutic efficacy of macrophage transplantation in the Il10rb -/- VEO-IBD mouse model. A 6-week regimen employing a combination of depletion of endogenous hyperinflammatory macrophages followed by intraperitoneal administration of wild-type macrophages significantly reduced colitis symptoms.

Conclusion: In summary, we show that the correction of the IL10 receptor-defect in macrophages either by genetic therapy or transfer of WT macrophages to the peritoneum can ameliorate disease-related symptoms and potentially represent novel treatment approaches for VEO-IBD patients.
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http://dx.doi.org/10.1093/ecco-jcc/jjab031DOI Listing
February 2021

Development and pilot testing of a web-based symptom management program for multiple sclerosis: My MS toolkit.

Rehabil Psychol 2021 May 4;66(2):224-232. Epub 2021 Feb 4.

Department of Rehabilitation Medicine, University of Washington.

We describe the process of working with stakeholders with multiple sclerosis (MS) to develop a web-based multisymptom self-management program to address chronic pain, fatigue, and/or depressive symptoms. The results of a pilot trial to test the feasibility and effects of the program are presented. The first study phase involved the development of a web-based symptom self-management program. The second phase involved a single-arm pilot trial ( = 20) of unguided website use for 12 weeks in adults with MS and elevated levels of chronic pain, fatigue, and/or depressed mood. A web-based symptom self-management program, My MS Toolkit, was developed and released for public use in 2019. The results from the pilot trial showed that on average, participants accessed the website 5.4 times, spending about 7 min on the site per visit. Eighty percent rated intervention-related changes in activity limitations, symptoms, emotions, and overall quality of life as either "somewhat" or "moderately" better. Although there were no significant improvements on outcome measures, of those who screened positive for the outcome of interest (i.e., showed a clinically elevated level of that symptom), clinically significant improvement was seen in 37.5% for fatigue, 45.5% for pain, and 40% for depressive symptoms. My MS Toolkit is an accessible, stakeholder-informed, web-based MS symptom self-management program that demonstrated a clinically significant positive impact on symptoms in a proportion of participants. More research is needed to further examine the effects of this program and elucidate who is most likely to benefit from this type of self-guided intervention. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/rep0000375DOI Listing
May 2021

Cannabidiol Use for Fibromyalgia: Prevalence of Use and Perceptions of Effectiveness in a Large Online Survey.

J Pain 2021 05 2;22(5):556-566. Epub 2021 Jan 2.

Anesthesiology Department, University of Michigan Medical School, Ann Arbor, Michigan.

Cannabidiol (CBD) is widely advertised as helpful for chronic pain management but research is limited. Using a cross-sectional, anonymous survey, we examined patterns of naturalistic CBD use among individuals with fibromyalgia (FM) and other chronic pain conditions. Our objective was to better understand rates of CBD use, reasons for use and discontinuation, communication with healthcare professionals about CBD, and perceptions of CBD effectiveness and safety among people with FM. After excluding incomplete surveys, our study population consisted of N = 2,701 participants with fibromyalgia, primarily in the United States. Overall, 38.1% reported never using CBD, 29.4% reported past CBD use, and 32.4% reported current CBD use. Past-year cannabis use was strongly associated with past or current CBD use. Those using CBD typically did so due to inadequate symptom relief, while those not using CBD typically cited safety concerns as their reason for not using CBD. Two-thirds of participants disclosed CBD use to their physician, although only 33% asked for physician advice on using CBD. Participants used CBD for numerous FM-related symptoms (most commonly pain), and generally reported slight to much improvement across symptom domains. Around half of participants reported side effects, which were typically minor. Our findings are limited by selection bias and our cross-sectional design, which prevents causal associations. In conclusion, CBD use is common among individuals with FM and many individuals using CBD report improvements across numerous FM-related symptoms. Our findings highlight the need for additional rigorous studies to better understand CBD's potential for FM management. PERSPECTIVE: This article indicates that CBD use is common among people with fibromyalgia, and the results suggest that many derive benefit from using CBD across multiple symptoms domains. Clinicians should discuss CBD use with fibromyalgia patients, and future studies are needed to rigorously assess CBD's therapeutic value for fibromyalgia symptoms.
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http://dx.doi.org/10.1016/j.jpain.2020.12.001DOI Listing
May 2021

Subgrouping a Large U.S. Sample of Patients with Fibromyalgia Using the Fibromyalgia Impact Questionnaire-Revised.

Int J Environ Res Public Health 2020 12 31;18(1). Epub 2020 Dec 31.

AGORA Research Group, Teaching, Research & Innovation Unit, Parc Sanitari Sant Joan de Déu, 08830 St. Boi de Llobregat, Spain.

Fibromyalgia (FM) is a heterogeneous and complex syndrome; different studies have tried to describe subgroups of FM patients, and a 4-cluster classification based on the Fibromyalgia Impact Questionnaire-Revised (FIQR) has been recently validated. This study aims to cross-validate this classification in a large US sample of FM patients. A pooled sample of 6280 patients was used. First, we computed a hierarchical cluster analysis (HCA) using FIQR scores at item level. Then, a latent profile analysis (LPA) served to confirm the accuracy of the taxonomy. Additionally, a cluster calculator was developed to estimate the predicted subgroup using an ordinal regression analysis. Self-reported clinical measures were used to examine the external validity of the subgroups in part of the sample. The HCA yielded a 4-subgroup distribution, which was confirmed by the LPA. Each cluster represented a different level of severity: "Mild-moderate", "moderate", "moderate-severe", and "severe". Significant differences between clusters were observed in most of the clinical measures (e.g., fatigue, sleep problems, anxiety). Interestingly, lower levels of education were associated with higher FM severity. This study corroborates a 4-cluster distribution based on FIQR scores to classify US adults with FM. The classification may have relevant clinical implications for diagnosis and treatment response.
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http://dx.doi.org/10.3390/ijerph18010247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796452PMC
December 2020

Qualitative Analysis of Treatment Needs in Interstitial Cystitis/Bladder Pain Syndrome: Implications for Intervention.

Can J Pain 2020 1;4(1):181-198. Epub 2020 Sep 1.

Department of Medicine, Vanderbilt University School of Medicine.

Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition carrying substantial psychosocial burden. Psychological treatment for IC/BPS is little studied, and there are barriers to its use in clinical management. Whether psychological treatments benefit patients with IC/BPS is unclear and we do not know if such treatments would meet patient needs.

Aims: Incorporating patient-reported needs and acknowledging diversity in pain experiences can inform patient-centered interventions for IC/BPS. This project characterized the experience of living with IC/BPS and patient perceptions of needs in its treatment, with the goal of informing patient-centered treatment for IC/BPS.

Methods: Using both quantitative and qualitative methods, 27 females with IC/BPS participated in a focus group and completed validated self-report assessments evaluating urinary symptoms, pain, and emotional functioning. Focus groups were audio recorded and transcribed, then coded and analyzed using an iterative inductive/deductive approach. Linear regression models evaluated the relationship between psychological functioning and symptom severity.

Results: We conducted six focus groups between 8/2017-12/2017. Five major themes emerged from qualitative analysis: managing physical symptoms, emotional symptoms, impact on daily life and socio-contextual factors, responding to illness, and addressing needs in treatment. The physiological and emotional consequences of IC/BPS were reported, highlighting their impact on interpersonal relationships and challenges obtaining appropriate treatment for IC/BPS. Quantitative analysis showed depression levels were significantly associated with worsened IC/BPS symptomology, after controlling for known confounding factors.

Conclusion: Individuals with IC/BPS could benefit from tailored psychological interventions focusing on pain management, emotion regulation, communications skills, along with sexual dysfunction and intimacy fears.
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http://dx.doi.org/10.1080/24740527.2020.1785854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751614PMC
September 2020

Post-Transcriptional Genetic Silencing of to Treat Sickle Cell Disease.

N Engl J Med 2021 01 5;384(3):205-215. Epub 2020 Dec 5.

From the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).

Background: Sickle cell disease is characterized by hemolytic anemia, pain, and progressive organ damage. A high level of erythrocyte fetal hemoglobin (HbF) comprising α- and γ-globins may ameliorate these manifestations by mitigating sickle hemoglobin polymerization and erythrocyte sickling. is a repressor of γ-globin expression and HbF production in adult erythrocytes. Its down-regulation is a promising therapeutic strategy for induction of HbF.

Methods: We enrolled patients with sickle cell disease in a single-center, open-label pilot study. The investigational therapy involved infusion of autologous CD34+ cells transduced with the BCH-BB694 lentiviral vector, which encodes a short hairpin RNA (shRNA) targeting mRNA embedded in a microRNA (shmiR), allowing erythroid lineage-specific knockdown. Patients were assessed for primary end points of engraftment and safety and for hematologic and clinical responses to treatment.

Results: As of October 2020, six patients had been followed for at least 6 months after receiving BCH-BB694 gene therapy; median follow-up was 18 months (range, 7 to 29). All patients had engraftment, and adverse events were consistent with effects of the preparative chemotherapy. All the patients who could be fully evaluated achieved robust and stable HbF induction (percentage HbF/(F+S) at most recent follow-up, 20.4 to 41.3%), with HbF broadly distributed in red cells (F-cells 58.9 to 93.6% of untransfused red cells) and HbF per F-cell of 9.0 to 18.6 pg per cell. Clinical manifestations of sickle cell disease were reduced or absent during the follow-up period.

Conclusions: This study validates BCL11A inhibition as an effective target for HbF induction and provides preliminary evidence that shmiR-based gene knockdown offers a favorable risk-benefit profile in sickle cell disease. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT03282656).
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http://dx.doi.org/10.1056/NEJMoa2029392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962145PMC
January 2021

Characterizing chronic pain phenotypes in multiple sclerosis: a nationwide survey study.

Pain 2021 05;162(5):1426-1433

Department of Neurology, University of Michigan, Ann Arbor, MI, United States.

Abstract: Chronic pain is highly prevalent in multiple sclerosis (MS). Pain heterogeneity may contribute to poor treatment outcomes. The aim of this study was to characterize pain phenotypes distributions in persons with MS and compare pain phenotypes in terms of pain intensity, frequency of chronic overlapping pain conditions, and use and analgesic effects of different classes of pain medications. Data were collected through a national web-based survey with measures of neuropathic (painDETECT) and nociplastic pain (Fibromyalgia Survey Criteria), chronic overlapping pain conditions, and pain medication use and pain relief. In a sample of N = 842 adults with chronic pain and MS, the largest proportion (41%) showed evidence of nociceptive pain, 27% had mixed neuropathic/nociplastic pain, 23% had nociplastic pain, and 9% had neuropathic pain. Nociplastic pain was associated with significantly higher pain intensity and frequency of chronic overlapping pain conditions. Across all pain types, high frequency of pain medication use along with poor-modest pain relief was reported. Cannabis use for pain was more common, and pain relief ratings were higher among those with nociplastic pain, relative to nociceptive pain. Although NSAID use was highest among those with nociplastic pain (80%), pain relief ratings for NSAIDs were highest among those with nociceptive pain. These findings underscore the need for multidimensional assessment of pain in MS with greater emphasis on the identification of pain phenotype. An improved characterization of pain as a multifaceted condition in MS could inform therapeutic approaches.
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http://dx.doi.org/10.1097/j.pain.0000000000002136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054538PMC
May 2021

Predictors of engagement in an internet-based cognitive behavioral therapy program for veterans with chronic low back pain.

Transl Behav Med 2021 06;11(6):1274-1282

Anesthesiology, Critical Care, and Pain Medicine Service, VA Boston Healthcare System, Boston, MA, USA.

Internet-based interventions for chronic pain have demonstrated efficacy and may address access barriers to care. Participant characteristics have been shown to affect engagement with these programs; however, limited information is available about the relationship between participant characteristics and engagement with internet-based programs for self-management of chronic pain. The current study examined relationships between demographic and clinical characteristics and engagement with the Pain EASE program, a self-directed, internet-based cognitive behavioral therapy intervention for veterans with chronic low back pain (cLBP). Veterans with cLBP were enrolled in a 10 week trial of the Pain EASE program. Engagement measures included the number of logins, access to coping skill modules, and completed study staff-initiated weekly check-in calls. Regression analyses were conducted to identify significant predictors of engagement from hypothesized predictors (e.g., race/ethnicity, age, depressive symptom severity, and pain interference). Participants (N = 58) were 93% male, 60.3% identified as White, and had a mean age of 54.5 years. Participants logged into the program a median of 3.5 times, accessed a median of 2 skill modules, and attended a median of 6 check-in calls. Quantile regression revealed that, at the 50th percentile, non-White-identified participants accessed fewer modules than White-identified participants (p = .019). Increased age was associated with increased module use (p = .001). No clinical characteristics were significantly associated with engagement measures. White-identified race/ethnicity and increased age were associated with greater engagement with the Pain EASE program. Results highlight the importance of defining and increasing engagement in internet-delivered pain care.
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http://dx.doi.org/10.1093/tbm/ibaa098DOI Listing
June 2021

Measures for the Assessment of Pain in Adults.

Arthritis Care Res (Hoboken) 2020 10;72 Suppl 10:342-357

University of Michigan, Ann Arbor.

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http://dx.doi.org/10.1002/acr.24222DOI Listing
October 2020

A study assessing the feasibility of randomization of pediatric and young adult patients between matched unrelated donor bone marrow transplantation and immune-suppressive therapy for newly diagnosed severe aplastic anemia: A joint pilot trial of the North American Pediatric Aplastic Anemia Consortium and the Pediatric Transplantation and Cellular Therapy Consortium.

Pediatr Blood Cancer 2020 10 9;67(10):e28444. Epub 2020 Aug 9.

Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.

Background: Recent data show survival after matched unrelated donor (MUD) bone marrow transplantation (BMT) is similar to matched sibling procedures for young patients with severe aplastic anemia (SAA). Donor delays, risk of transplant-related mortality (TRM), and concern about chronic graft versus host disease raise questions about whether MUD BMT or immune suppression therapy (IST) should be preferred initial therapy for young patients lacking matched sibling donors.

Procedure: We performed a pilot trial to assess the feasibility of randomizing patients under age 26 with newly diagnosed SAA to receive IST versus MUD BMT. Primary aims assessed the acceptability of randomization and timing of BMT. Secondary aims measured toxicities, response, and survival.

Results: Sixty-seven patients with possible SAA were screened at nine centers. Of 57 with confirmed SAA, 23 underwent randomization and received therapy with a median follow-up of 18 months. Of 12 randomized to BMT, 10 started BMT as initial therapy at a median of 36 days after randomization. One BMT recipient experienced secondary graft failure, requiring a second procedure. Six of 11 randomized to IST responded, whereas five with refractory disease underwent successful salvage BMT. One patient achieving complete response relapsed after discontinuation of immune suppression and died of infection after salvage BMT.

Conclusions: This feasibility study showed that a high percentage of patients underwent randomization and received up-front MUD BMT. Our study lays the groundwork for a larger randomized trial that will define best initial therapy for young patients with SAA who have an available MUD.
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http://dx.doi.org/10.1002/pbc.28444DOI Listing
October 2020

Peripheral blood smears of children with multisystem inflammatory syndrome demonstrate prominence of early myeloid forms with morphologic evidence of toxic change.

Pediatr Blood Cancer 2021 01 24;68(1):e28551. Epub 2020 Jul 24.

Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1002/pbc.28551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404579PMC
January 2021

Children's rare disease cohorts: an integrative research and clinical genomics initiative.

NPJ Genom Med 2020 6;5:29. Epub 2020 Jul 6.

Computational Health Informatics Program, Boston Children's Hospital, Boston, MA 02115 USA.

While genomic data is frequently collected under distinct research protocols and disparate clinical and research regimes, there is a benefit in streamlining sequencing strategies to create harmonized databases, particularly in the area of pediatric rare disease. Research hospitals seeking to implement unified genomics workflows for research and clinical practice face numerous challenges, as they need to address the unique requirements and goals of the distinct environments and many stakeholders, including clinicians, researchers and sequencing providers. Here, we present outcomes of the first phase of the Children's Rare Disease Cohorts initiative (CRDC) that was completed at Boston Children's Hospital (BCH). We have developed a broadly sharable database of 2441 exomes from 15 pediatric rare disease cohorts, with major contributions from early onset epilepsy and early onset inflammatory bowel disease. All sequencing data is integrated and combined with phenotypic and research data in a genomics learning system (GLS). Phenotypes were both manually annotated and pulled automatically from patient medical records. Deployment of a genomically-ordered relational database allowed us to provide a modular and robust platform for centralized storage and analysis of research and clinical data, currently totaling 8516 exomes and 112 genomes. The GLS integrates analytical systems, including machine learning algorithms for automated variant classification and prioritization, as well as phenotype extraction via natural language processing (NLP) of clinical notes. This GLS is extensible to additional analytic systems and growing research and clinical collections of genomic and other types of data.
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http://dx.doi.org/10.1038/s41525-020-0137-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338382PMC
July 2020

P2X7 receptor antagonism inhibits tumour growth in human high-grade gliomas.

Purinergic Signal 2020 09 24;16(3):327-336. Epub 2020 Jun 24.

Department of Neuroscience, Central Clinical School, Monash University, Level 6, 99 Commercial Rd, Melbourne, VIC, 3004, Australia.

Gliomas, the most common primary brain cancer, are highly infiltrative and extremely difficult to treat. Despite advancements, current treatment is limited, with patients surviving for a median of 14-15 months post-diagnosis. Previous research has demonstrated the upregulation of a purinergic receptor, P2X7R, in human gliomas. P2X7R is expressed on both glioma cells and microglia within the glioma microenvironment. It is hypothesized that P2X7R contributes to tumour growth and proliferation via immune-mediated mechanisms involving tumour cells and surrounding microglia. We sought to elucidate the role of P2X7R in a human glioblastoma cell line (U251) and on surgically resected human glioma samples. We treated U251 and human glioma cultures for 72 h with P2X7R antagonists, Brilliant Blue G (BBG), oxidized ATP (oATP) and AZ10606120. Cell counting via fluorescence confocal microscopy was conducted to assess tumour proliferation. We observed no significant reductions in tumour cell numbers following P2X7R antagonism with BBG (20 μM) and oATP (250 μM) in both U251 cells and human glioma samples. Interestingly, there was a significant reduction in tumour cell number in both U251 cells (p = 0.0156) and human glioma samples (p = 0.0476) treated with varying concentrations of AZ10606120. When compared with the conventional chemotherapeutic agent, temozolomide, AZ10606120 was also found to more effectively inhibit tumour proliferation in U251 cells (p < 0.0001). Our pilot results demonstrate a potential trophic role of P2X7R where its inhibition by AZ10606120, a potent antagonist, hinders glioma growth directly or through the inactivation of microglia. This sheds new light on P2X7R as a therapeutic target for human gliomas.
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http://dx.doi.org/10.1007/s11302-020-09705-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524927PMC
September 2020

The Multidisciplinary Approach to The Study of Chronic Pelvic Pain (MAPP) Research Network*: Design and implementation of the Symptom Patterns Study (SPS).

Neurourol Urodyn 2020 08 23;39(6):1803-1814. Epub 2020 Jun 23.

Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Aims: The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network initiated a second observational cohort study-the Symptom Patterns Study (SPS)-to further investigate the underlying pathophysiology of Urologic Chronic Pelvic Pain Syndrome (UCPPS) and to discover factors associated with longitudinal symptom changes and responses to treatments.

Methods: This multisite cohort study of males and females with UCPPS features a run-in period of four weekly web-based symptom assessments before a baseline visit, followed by quarterly assessments up to 36 months. Controls were also recruited and assessed at baseline and 6 months. Extensive clinical data assessing urological symptoms, nonurological pain, chronic overlapping pain syndromes, and psychosocial factors were collected. Diverse biospecimens for biomarker and microbiome studies, quantitative sensory testing (QST) data under multiple stimuli, and structural and functional neuroimaging scans were obtained under a standardized protocol.

Results: Recruitment was initiated (July 2015) and completed (February 2019) at six discovery sites. A total of 620 males and females with UCPPS and 73 Controls were enrolled, including 83 UCPPS participants who re-enrolled from the first MAPP Network cohort study (2009-2012). Baseline neuroimaging scans, QST measures, and biospecimens were obtained on 578 UCPPS participants. The longitudinal follow-up of the cohort is ongoing.

Conclusions: This comprehensive characterization of a large UCPPS cohort with extended follow-up greatly expands upon earlier MAPP Network studies and provides unprecedented opportunities to increase our understanding of UCPPS pathophysiology, factors associated with symptom change, clinically relevant patient phenotypes, and novel targets for future interventions.
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http://dx.doi.org/10.1002/nau.24423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025696PMC
August 2020

HACE1 Prevents Lung Carcinogenesis via Inhibition of RAC-Family GTPases.

Cancer Res 2020 07 4;80(14):3009-3022. Epub 2020 May 4.

Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna BioCentre, Vienna, Austria.

HACE1 is an E3 ubiquitin ligase with important roles in tumor biology and tissue homeostasis. Loss or mutation of has been associated with the occurrence of a variety of neoplasms, but the underlying mechanisms have not been defined yet. Here, we report that is frequently mutated in human lung cancer. In mice, loss of led to enhanced progression of -driven lung tumors. Additional ablation of the oncogenic GTPase partially reduced progression of lung tumors. RAC2, a novel ubiquitylation target of HACE1, could compensate for the absence of its homolog RAC1 in -deficient, but not in HACE1-sufficient tumors. Accordingly, ablation of both and fully averted the increased progression of -driven lung tumors in mice. In patients with lung cancer, increased expression of correlated with reduced levels of and and prolonged survival, whereas elevated expression of and was associated with poor prognosis. This work defines HACE1 as a crucial regulator of the oncogenic activity of RAC-family GTPases in lung cancer development. SIGNIFICANCE: These findings reveal that mutation of the tumor suppressor HACE1 disrupts its role as a regulator of the oncogenic activity of RAC-family GTPases in human and murine lung cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/14/3009/F1.large.jpg.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-2270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611202PMC
July 2020

The Changing Face of Adrenoleukodystrophy.

Endocr Rev 2020 08;41(4)

Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts.

Adrenoleukodystrophy (ALD) is a rare X-linked disorder of peroxisomal oxidation due to mutations in ABCD1. It is a progressive condition with a variable clinical spectrum that includes primary adrenal insufficiency, myelopathy, and cerebral ALD. Adrenal insufficiency affects over 80% of ALD patients. Cerebral ALD affects one-third of boys under the age of 12 and progresses to total disability and death without treatment. Hematopoietic stem cell transplantation (HSCT) remains the only disease-modifying therapy if completed in the early stages of cerebral ALD, but it does not affect the course of adrenal insufficiency. It has significant associated morbidity and mortality. A recent gene therapy clinical trial for ALD reported short-term MRI and neurological outcomes comparable to historical patients treated with HSCT without the associated adverse side effects. In addition, over a dozen states have started newborn screening (NBS) for ALD, with the number of states expecting to double in 2020. Genetic testing of NBS-positive neonates has identified novel variants of unknown significance, providing further opportunity for genetic characterization but also uncertainty in the monitoring and therapy of subclinical and/or mild adrenal insufficiency or cerebral involvement. As more individuals with ALD are identified at birth, it remains uncertain if availability of matched donors, transplant (and, potentially, gene therapy) centers, and specialists may affect the timely treatment of these individuals. As these promising gene therapy trials and NBS transform the clinical management and outcomes of ALD, there will be an increasing need for the endocrine management of presymptomatic and subclinical adrenal insufficiency. (Endocrine Reviews 41: 1 - 17, 2020).
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http://dx.doi.org/10.1210/endrev/bnaa013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286618PMC
August 2020

Infantile Myelofibrosis and Myeloproliferation with CDC42 Dysfunction.

J Clin Immunol 2020 05 17;40(4):554-566. Epub 2020 Apr 17.

Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Studies of genetic blood disorders have advanced our understanding of the intrinsic regulation of hematopoiesis. However, such genetic studies have only yielded limited insights into how interactions between hematopoietic cells and their microenvironment are regulated. Here, we describe two affected siblings with infantile myelofibrosis and myeloproliferation that share a common de novo mutation in the Rho GTPase CDC42 (Chr1:22417990:C>T, p.R186C) due to paternal germline mosaicism. Functional studies using human cells and flies demonstrate that this CDC42 mutant has altered activity and thereby disrupts interactions between hematopoietic progenitors and key tissue microenvironmental factors. These findings suggest that further investigation of this and other related disorders may provide insights into how hematopoietic cell-microenvironment interactions play a role in human health and can be disrupted in disease. In addition, we suggest that deregulation of CDC42 may underlie more common blood disorders, such as primary myelofibrosis.
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http://dx.doi.org/10.1007/s10875-020-00778-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253386PMC
May 2020

Preclinical Evaluation of a Novel Lentiviral Vector Driving Lineage-Specific BCL11A Knockdown for Sickle Cell Gene Therapy.

Mol Ther Methods Clin Dev 2020 Jun 17;17:589-600. Epub 2020 Mar 17.

Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA.

In this work we provide preclinical data to support initiation of a first-in-human trial for sickle cell disease (SCD) using an approach that relies on reversal of the developmental fetal-to-adult hemoglobin switch. Erythroid-specific knockdown of BCL11A via a lentiviral-encoded microRNA-adapted short hairpin RNA (shRNA) leads to reactivation of the gamma-globin gene while simultaneously reducing expression of the pathogenic adult sickle β-globin. We generated a refined lentiviral vector (LVV) BCH-BB694 that was developed to overcome poor vector titers observed in the manufacturing scale-up of the original research-grade LVV. Healthy or sickle cell donor CD34 cells transduced with Good Manufacturing Practices (GMP)-grade BCH-BB694 LVV achieved high vector copy numbers (VCNs) >5 and gene marking of >80%, resulting in a 3- to 5-fold induction of fetal hemoglobin (HbF) compared with mock-transduced cells without affecting growth, differentiation, and engraftment of gene-modified cells or . immortalization assays, which are designed to measure vector-mediated genotoxicity, showed no increased immortalization compared with mock-transduced cells. Together these data demonstrate that BCH-BB694 LVV is non-toxic and efficacious in preclinical studies, and can be generated at a clinically relevant scale in a GMP setting at high titer to support clinical testing for the treatment of SCD.
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http://dx.doi.org/10.1016/j.omtm.2020.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150438PMC
June 2020

Pressure Pain Tolerance Predicts the Success of Emotional Awareness and Expression Therapy in Patients With Fibromyalgia.

Clin J Pain 2020 07;36(7):562-566

Department of Anesthesiology, Chronic Pain and Fatigue Research Center.

Objectives: Quantitative sensory testing may help predict treatment responses in individuals with chronic pain. Our objective was to determine whether evoked pain sensitivity at baseline predicted preferential treatment responses to either emotional awareness and expression therapy (EAET) or cognitive behavioral therapy (CBT) in individuals with fibromyalgia (FM).

Methods: This was a secondary analysis of a previous randomized clinical trial, in which individuals with FM were randomized to EAET, CBT, or Education as a control intervention. Only females who completed baseline and post-treatment assessments were analyzed (n=196). The primary outcome was change in overall clinical pain severity from pretreatment to posttreatment, and the primary predictor of interest was pressure pain tolerance at baseline.

Results: Among patients with low pain tolerance at baseline (n=154), both EAET and CBT led to small but significant improvements in clinical pain severity (CBT mean=0.66, 95% confidence interval [0.24-1.07]; EAET mean=0.76 [0.34-1.17]). Conversely, in patients with normal pain tolerance (n=42), there was no significant improvement in clinical pain after CBT (0.13 [-0.88 to 1.14]), a small improvement after FM Education (0.81 [0.14-1.48]), but a much larger and statistically significant improvement after EAET (2.14 [1.23-3.04]).

Discussion: Normal levels of pressure pain tolerance at baseline predicted greater improvement in clinical pain severity after EAET than CBT. Quantitative sensory testing may provide insights about individual responses to psychologically based therapies for individuals with chronic pain.
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http://dx.doi.org/10.1097/AJP.0000000000000829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272255PMC
July 2020

The Role of Environmental Distractions in the Experience of Fibrofog in Real-World Settings.

ACR Open Rheumatol 2020 Apr 1;2(4):214-221. Epub 2020 Apr 1.

Pennsylvania State University, University Park, Pennsylvania.

Objective: Perceived cognitive dysfunction in people with fibromyalgia (FM), "fibrofog," is commonly reported and has been demonstrated in neurocognitive testing. Distractibility and inattention have been implicated as potential contributors to fibrofog, but the role of environmental distractions has not been explored. In this study, ambulatory assessment methods were used to examine whether FM is related to more environmental distractions and to examine the impact of distractions on subjective and objective cognitive functioning.

Methods: Fifty people with FM and 50 age-, sex-, and education-matched controls without FM completed 8 consecutive days of ambulatory assessments. Five times per day, participants reported perceived cognitive functioning and environmental distractions and completed validated tests of processing speed and working memory.

Results: The FM group reported distractions in a higher proportion of the ambulatory cognitive testing sessions (40.5%) compared with the group without FM (29.8%; P < 0.001) and more often reported multiple simultaneous distractions. For both groups, sound was the most common distraction. The group with FM reported more distractions caused by light, and the group without FM reported more social distractions. Group differences in subjective and objective cognitive functioning were not augmented during distraction relative to during periods of no distraction. There were no group differences in within-person changes in cognitive functioning as a function of distraction.

Conclusion: The group with FM reported more distractions than the group without FM; both groups reported poorer processing speed when distracted, and the effects of distraction on test performance did not differ significantly by group. Findings suggest that sensitivity to environmental distractions may play a role in the experience of cognitive dysfunction in FM.
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http://dx.doi.org/10.1002/acr2.11130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164629PMC
April 2020

Current and future gene therapies for hemoglobinopathies.

Curr Opin Hematol 2020 05;27(3):149-154

Division of Hematology/Oncology, Boston Children's Hospital.

Purpose Of Review: In this work we briefly summarize the key features and currently available conventional therapies for the two main β-hemoglobinopathies, sickle cell disease (SCD) and β-thalassemia, and review the rapidly evolving field of novel and emerging genetic therapies to cure the disease.

Recent Findings: Gene therapy using viral vectors or designer nuclease-based gene editing is a relatively new field of medicine that uses the patient's own genetically modified cells to treat his or her own disease. Multiple different approaches are currently in development, and some have entered phase I clinical studies, including innovative therapies aiming at induction of fetal hemoglobin.

Summary: Early short-term therapeutic benefit has been reported for some of the ongoing clinical trials, but confirmation of long-term safety and efficacy remains to be shown. Future therapies aiming at the targeted correction of specific disease-causing DNA mutations are emerging and will likely enter clinical testing in the near future.
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http://dx.doi.org/10.1097/MOH.0000000000000581DOI Listing
May 2020

Lentiviral gene therapy for X-linked chronic granulomatous disease.

Nat Med 2020 02 27;26(2):200-206. Epub 2020 Jan 27.

Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK.

Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells. We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34 hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685). The primary objectives were to assess the safety and evaluate the efficacy and stability of biochemical and functional reconstitution in the progeny of engrafted cells at 12 months. The secondary objectives included the evaluation of augmented immunity against bacterial and fungal infection, as well as assessment of hematopoietic stem cell transduction and engraftment. Two enrolled patients died within 3 months of treatment from pre-existing comorbidities. At 12 months, six of the seven surviving patients demonstrated stable vector copy numbers (0.4-1.8 copies per neutrophil) and the persistence of 16-46% oxidase-positive neutrophils. There was no molecular evidence of either clonal dysregulation or transgene silencing. Surviving patients have had no new CGD-related infections, and six have been able to discontinue CGD-related antibiotic prophylaxis. The primary objective was met in six of the nine patients at 12 months follow-up, suggesting that autologous gene therapy is a promising approach for CGD patients.
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http://dx.doi.org/10.1038/s41591-019-0735-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115833PMC
February 2020

A Simple and Reliable Protocol for the Preparation and Culturing of Fresh Surgically Resected Human Glioblastoma Tissue.

Methods Protoc 2020 Jan 22;3(1). Epub 2020 Jan 22.

Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia.

Glioblastoma is a heterogeneous glial cell malignancy with extremely high morbidity and mortality. Current treatment is limited and provide minimal therapeutic efficacy. Previous studies were reliant on cell lines that do not accurately reflect the heterogeneity of the glioma microenvironment. Developing reliable models of human glioblastoma is therefore essential. Direct culture of human brain tumours is often difficult and there is a limited number of protocols available. Hence, we have developed an effective method for the primary culture of human glioblastoma samples obtained during surgical resection. Culturing tumour tissue direct from human brain is advantageous in that cultures (1) more closely resemble true human disease, relative to the use of cell lines; (2) comprise a range of cellular components present in the natural tumour microenvironment; and (3) are free of added antibodies and reagents. Additionally, primary glioblastoma cultures are valuable in studies examining the effects of anti-cancer pharmaceuticals and therapeutic agents, and can be further used in live cell imaging, immunocytochemistry, flow cytometry and immunoassay experiments. Via this protocol, cells are maintained in supplemented medium at 37 °C (5% CO) and are expected to achieve sufficient confluency within 7 days of initial culture.
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http://dx.doi.org/10.3390/mps3010011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189671PMC
January 2020

A MAPP Network Case-control Study of Urological Chronic Pelvic Pain Compared With Nonurological Pain Conditions.

Clin J Pain 2020 01 26;36(1):8-15. Epub 2019 Sep 26.

Departments of Anesthesiology, Medicine, and Psychiatry, University of Michigan, Ann Arbor, MI.

Objectives: Limited research suggests commonalities between urological chronic pelvic pain syndromes (UCPPS) and other nonurological chronic overlapping pain conditions (COPCs) including fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome. The goal of this case-control study was to examine similarities and differences between UCPPS and these other COPCs.

Materials And Methods: As part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research (MAPP) Network, we examined 1039 individuals with UCPPS (n=424), nonurological COPCs (n=200), and healthy controls (HCs; n=415). Validated standardized measures were used to assess urological symptoms, nonurological pain symptoms, and psychosocial symptoms and traits.

Results: Participants with UCPPS had more urological symptoms than nonurological COPCs or HCs (P<0.001); nonurological COPC group also had significantly worse urological symptoms than HCs (P<0.001). Participants with nonurological COPCs reported more widespread pain than those with UCPPS (P<0.001), yet both groups had similarly increased symptoms of anxiety, depression, negative affect, perceived stress, neuroticism, and lower levels of extraversion than HCs (P<0.001). Participants with UCPPS with and without COPCs reported more catastrophizing than those with nonurological COPCs (P<0.001).

Discussion: Findings are consistent with the hypothesis of common underlying biopsychosocial mechanisms and can guide the comprehensive assessment and treatment of these conditions regardless of the primary site of pain or diagnosis. Heightened catastrophizing in UCPPS should be examined to inform psychosocial interventions and improve patient care.
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http://dx.doi.org/10.1097/AJP.0000000000000769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055954PMC
January 2020

Internet-Based Pain Self-Management for Veterans: Feasibility and Preliminary Efficacy of the Pain EASE Program.

Pain Pract 2020 04 28;20(4):357-370. Epub 2020 Jan 28.

Yale School of Medicine, New Haven, Connecticut.

Objective: To develop and test the feasibility and preliminary efficacy of a cognitive behavioral therapy-based, internet-delivered self-management program for chronic low back pain (cLBP) in veterans.

Methods: Phase I included program development, involving expert panel and participant feedback. Phase II was a single-arm feasibility and preliminary efficacy study of the Pain e-health for Activity, Skills, and Education (Pain EASE) program. Feasibility (ie, website use, treatment credibility, satisfaction) was measured using descriptive methods. Mixed models were used to assess mean within-subject changes from baseline to 10 weeks post-baseline in pain interference (primary outcome, West Haven-Yale Multidimensional Pain Inventory, scale of 0 to 6), pain intensity, mood, fatigue, sleep, and depression.

Results: Phase I participants (n = 15) suggested modifications including style changes, content reduction, additional "Test Your Knowledge" quizzes, and cognitive behavioral therapy skill practice monitoring form revisions for enhanced usability. In Phase II, participants (n = 58) were mostly male (93%) and White (60%), and had an average age of 55 years (standard deviation [SD] = 12) and moderate pain (mean score 5.9/10); 41 (71%) completed the post-baseline assessment. Participants (N = 58) logged on 6.1 (SD = 8.6) times over 10 weeks, and 85% reported being very or moderately satisfied with Pain EASE. Pain interference improved from a mean of 3.8 at baseline to 3.3 at 10 weeks (difference 0.5 [95% confidence interval 0.1 to 0.9], P = 0.008). Within-subject improvement also occurred for some secondary outcomes, including mood and depression symptoms.

Discussion: Veterans with cLBP may benefit from technology-delivered interventions, which may also reduce pain interference. Overall, veterans found that Pain EASE, an internet-based self-management program, is feasible and satisfactory for cLBP.
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http://dx.doi.org/10.1111/papr.12861DOI Listing
April 2020
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