Publications by authors named "Michael Green"

1,482 Publications

  • Page 1 of 1

Bone Metastases, Skeletal-Related Events, and Survival in Patients With Metastatic Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors.

J Natl Compr Canc Netw 2021 Apr 20:1-7. Epub 2021 Apr 20.

3Division of Medical Oncology, and.

Background: Bone metastases and skeletal-related events (SREs) are a frequent cause of morbidity in patients with metastatic non-small cell lung cancer (mNSCLC). Data are limited on bone metastases and SREs in patients with mNSCLC treated using immune checkpoint inhibitors (ICIs), and on the efficacy of bone-modifying agents (BMAs) in this setting. Here we report the incidence, impact on survival, risk factors for bone metastases and SREs, and impact of BMAs in patients with mNSCLC treated with ICIs in a multi-institutional cohort.

Patients And Methods: We conducted a retrospective study of patients with mNSCLC treated with ICIs at 2 tertiary care centers from 2014 through 2017. Overall survival (OS) was compared between patients with and without baseline bone metastases using a log-rank test. A Cox regression model was used to evaluate the association between OS and the presence of bone metastases at ICI initiation, controlling for other confounding factors.

Results: We identified a cohort of 330 patients who had received ICIs for metastatic disease. Median patient age was 63 years, most patients were treated in the second line or beyond (n=259; 78%), and nivolumab was the most common ICI (n=211; 64%). Median OS was 10 months (95% CI, 8.4-12.0). In our cohort, 124 patients (38%) had baseline bone metastases, and 43 (13%) developed SREs during or after ICI treatment. Patients with bone metastases had a higher hazard of death after controlling for performance status, histology, line of therapy, and disease burden (hazard ratio, 1.57; 95% CI, 1.19-2.08; P=.001). Use of BMAs was not associated with OS or a decreased risk of SREs.

Conclusions: Presence of bone metastases at baseline was associated with a worse prognosis for patients with mNSCLC treated with ICI after controlling for multiple clinical characteristics. Use of BMAs was not associated with reduced SREs or a difference in survival.
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http://dx.doi.org/10.6004/jnccn.2020.7668DOI Listing
April 2021

Adult-onset asthma and periocular xanthogranuloma - A rare infiltrative disease of the orbit and eyelid.

Am J Ophthalmol Case Rep 2021 Jun 21;22:101043. Epub 2021 Mar 21.

Veterans Affairs Boston Healthcare System, Department of Ophthalmology, 150 South Huntington Avenue, Boston, MA, 02130, USA.

Purpose: To present a case of adult onset asthma with periocular xanthogranuloma (AAPOX), and discuss existing literature on adult orbital xanthogranulomatous diseases (AOXGDs) and their treatment.

Observations: A 63 year old male presented with progressive bilateral eyelid swelling with overlying yellow plaques associated with asthma. CT scan showed periorbital swelling with enlargement of the superior and lateral rectus muscles bilaterally. Biopsy demonstrated orbital xanthogranulomatous disease with increased IgG4 plasma cells. The patient was treated with intralesional triamcinolone, oral prednisone, and cyclophosphamide without significant improvement. Surgical debulking was eventually performed which improved his external symptoms until he was lost to follow up 15 months later.

Conclusions And Importance: AOXGDs are a group of rare infiltrative diseases of the eyelids and orbit that can be associated with significant systemic morbidities. While they all have similar underlying histopathologic features, appreciating the clinical difference between these diseases is important in understanding patient prognosis and ensuring appropriate clinical monitoring. There is also growing research demonstrating that AAPOX, along with other AOXGDs, may represent part of a continuum of IgG4 related disease, similar to what is seen in this case. There is currently no reliably effective treatment for AOXGDs, and additional research into the management of these diseases is necessary.
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http://dx.doi.org/10.1016/j.ajoc.2021.101043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044650PMC
June 2021

Use of Model-Based Compartmental Analysis and Theoretical Data to Further Explore Choice of Sampling Time for Assessing Vitamin A Status in Groups and Individual Human Subjects by the Retinol Isotope Dilution Method.

J Nutr 2021 Apr 8. Epub 2021 Apr 8.

Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, PA, USA.

Background: An optimal blood sampling time for application of the retinol isotope dilution (RID) method for predicting vitamin A total body stores (TBS) (i.e., vitamin A status) has not been established.

Objectives: Objectives were to identify sampling times that provide accurate estimates of TBS by RID in groups and individuals by applying compartmental modeling to data for theoretical adults and children.

Methods: We selected previously generated hypothetical adults and children (20 per group) that had a wide range of assigned values for TBS and vitamin A kinetic parameters. We used the Simulation, Analysis and Modeling software to simulate individual kinetic responses; then we calculated geometric mean values for the RID equation coefficients and each individual's plasma retinol specific activity at various times, using those values to predict group mean and individual subject TBS. Predicted values for TBS were compared with assigned values.

Results: Accurate estimates of group mean TBS were obtained at all sampling times from 1 to 30 d in both adults and children. For individuals, correlations between RID-predicted TBS and assigned values increased with time in the adults (R2 = 0.80 at day 14, 0.96 at day 21, and 0.99 at day 28); a similar trend was observed for the children, with R2 = 0.82 at day 7 and increasing to 0.97 at days 21 and 28 (P < 0.001 for all comparisons).

Conclusions: Although no single, unique time provided the most accurate prediction of TBS for all individuals within these groups, applying the RID method at 21 or 28 d yielded predictions that were within 25% of assigned values for 90% or 95% of adults, respectively; corresponding values for children were 80% from 10 to 20 d, and 85% at 21 and 28 d. For most subjects, early times (<14 d for adults and <10 d for children) provided less accurate predictions.
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http://dx.doi.org/10.1093/jn/nxab061DOI Listing
April 2021

Clinical and functional effects of the COVID-19 pandemic and social distancing on vulnerable veterans with psychosis or recent homelessness.

J Psychiatr Res 2021 Mar 29;138:42-49. Epub 2021 Mar 29.

Research Enhancement and Award Program on Enhancing Community Integration for Homeless Veterans, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA; Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.

The COVID-19 pandemic has upended the lives of everyone in the United States, negatively impacting social interactions, work, and living situations, and potentially exacerbating mental health issues in vulnerable individuals. Within the Department of Veterans Affairs (VA) healthcare system, two vulnerable groups include those with a psychotic disorder (PSY) and those who have recently experienced homelessness (recently housed Veterans, RHV). We conducted phone interviews with PSY (n = 81), RHV (n = 76) and control Veterans (CTL, n = 74) between mid-May - mid-August 2020 ("initial") and between mid-August - mid-October 2020 ("follow-up"). At the initial period, we also collected retrospective ratings relative to January 2020 ("pre-COVID-19"). We assessed clinical factors (e.g., depression, anxiety, loneliness) and community integration (e.g., social and role functioning). All groups reported worse clinical outcomes after the onset of the COVID-19 pandemic. However, PSY and RHV exhibited improvements in depression and anxiety from initial to follow up, whereas CTL continued to exhibit elevated levels. There was little change in community integration measures. Our results indicate that all groups reported increased mental health problems after the onset of the pandemic, but vulnerable Veterans were not disproportionately affected and had better mental health resilience (i.e., for depression and anxiety) as the pandemic progressed compared to CTL. This effect could be due to the availability and utilization of VA services for PSY and RHV (e.g., housing and financial support, medical and mental health services), which may have helped to mitigate the impact of the pandemic.
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http://dx.doi.org/10.1016/j.jpsychires.2021.03.051DOI Listing
March 2021

Cloning Polymerase Chain Reaction (PCR) Products: Blunt-End Cloning.

Cold Spring Harb Protoc 2021 Apr 1;2021(4):pdb.prot101287. Epub 2021 Apr 1.

The following is an elegant and simple protocol for generating and cloning blunt-ended DNA. Incubation of a ligation reaction in the presence of an excess amount of restriction enzyme can dramatically increase the yield of recombinant plasmids. The role of the restriction enzyme is to cleave circular and linear concatemers at restriction sites that are regenerated when plasmid molecules ligate to themselves. The method requires that ligation of the plasmid to a target DNA molecule destroys the restriction site, so preventing the restriction enzyme from digesting recombinants generated during the ligation reaction. The net effect of constant reclamation of unit-length linear vector molecules is to drive the equilibrium of the ligation reaction strongly in favor of recombinants between vector and insert. The method is efficient because regeneration of vector DNA, ligation, and polishing the termini of PCR-generated fragments of DNA all occur simultaneously in the same reaction mixture.
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http://dx.doi.org/10.1101/pdb.prot101287DOI Listing
April 2021

Cloning Polymerase Chain Reaction Products: Addition of Restriction Sites to the Termini of Amplified DNA.

Cold Spring Harb Protoc 2021 Apr 1;2021(4):pdb.prot101279. Epub 2021 Apr 1.

To generate polymerase chain reaction (PCR) products that can be directionally cloned into a vector, different restriction sites are built into the forward and reverse primers that are used in the PCR. After PCR, the amplified product is purified, cleaved with the appropriate restriction enzymes, ligated into a vector with compatible cohesive ends, and used to transform .
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http://dx.doi.org/10.1101/pdb.prot101279DOI Listing
April 2021

Subtype-specific and co-occurring genetic alterations in B-cell non-Hodgkin lymphoma.

Haematologica 2021 Apr 1. Epub 2021 Apr 1.

Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Center for Cancer Epigenetics, University of Texas MD Anderson Cancer Center, Houston, TX.

B-cell non-Hodgkin's lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL such as diffuse large B-cell lymphoma (DLBCL) have been comprehensively interrogated at the genomic level. But rarer subtypes such as mantle cell lymphoma (MCL) remain sparsely characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 685 B-NHL tumors at high depth; including DLBCL, MCL, follicular lymphoma (FL), and Burkitt lymphoma (BL). We identified conserved hallmarks of B-NHL that were deregulated in the majority of tumor from each subtype, including the frequent genetic deregulation of the ubiquitin proteasome system (UPS). In addition, we identified subtype-specific patterns of genetic alterations, including clusters of co-occurring mutations and DNA copy number alterations. The cumulative burden of mutations within a single cluster were more discriminatory of B-NHL subtypes than individual mutations, implicating likely patterns of genetic cooperation that contribute to disease etiology. We therefore provide the first cross-sectional analysis of mutations and DNA copy number alterations across major B-NHL subtypes and a framework of co-occurring genetic alterations that deregulate genetic hallmarks and likely cooperate in lymphomagenesis.
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http://dx.doi.org/10.3324/haematol.2020.274258DOI Listing
April 2021

Predicting response to cognitive training for schizophrenia using results from two studies with different outcomes.

Schizophr Res 2021 Mar 23;231:61-66. Epub 2021 Mar 23.

New York State Psychiatric Institute, Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, and New York-Presbyterian, 1051 Riverside Drive, New York, NY 10032, United States. Electronic address:

Background: Collaborative data sharing between research groups provides an opportunity to explore the basis for the heterogeneity in cognitive training outcomes reported in the schizophrenia literature. The current analyses focused on the contribution of site and participant characteristics to these heterogeneous outcomes.

Methods: Data from two independent studies, from New York (NY) and Los Angeles (LA), were combined to yield a sample of 132 outpatient adults with schizophrenia/schizoaffective disorder. While similar treatment doses, cognitive exercises and outcome measures were used, sites differed in use of coaching, group discussion and compensation. Between-site differences in participant demographic and baseline clinical characteristics were tested. Regression examined predictors of change in cognition (MCCB) and functional capacity (UPSA) which could explain site differences in treatment effects.

Results: Medium to large treatment effect size differences in MCCB and UPSA favored the NY site over LA. When the studies were combined, the effect of site was significant for both outcomes with a medium effect size difference. After controlling for background characteristics, the effect of site was reduced for both outcomes, but remained significant for cognition. Improvement in UPSA was associated with better baseline MCCB (p < 0.001), lower baseline UPSA (p < 0.001) and younger age (p = 0.019). The overall model with site, baseline scores, and participant background characteristics explained about 30% to 40% of the variance in outcomes.

Discussion: Participant and treatment characteristics are both predictive of outcomes, but treatment characteristics may be more consequential to cognitive gain, while participant characteristics may be more consequential to change in functional capacity.
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http://dx.doi.org/10.1016/j.schres.2021.03.006DOI Listing
March 2021

Awareness of illness is associated with better social and nonsocial cognition in recent-onset schizophrenia.

Schizophr Res 2021 Mar 23;231:51-53. Epub 2021 Mar 23.

Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America; Department of Psychology, University of California Los Angeles, Los Angeles, CA, United States of America; Semel Institute for Neuroscience and Human Behavior at UCLA, United States of America.

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http://dx.doi.org/10.1016/j.schres.2021.02.020DOI Listing
March 2021

Pre-school childcare and inequalities in child development.

SSM Popul Health 2021 Jun 12;14:100776. Epub 2021 Mar 12.

MRC/CSO Social & Public Health Sciences Unit, University of Glasgow, 99 Berkeley Street, Glasgow, G3 7HR, United Kingdom.

Centre-based childcare may benefit pre-school children and alleviate inequalities in early childhood development, but evidence on socio-emotional and physical health outcomes is limited. Data were from the UK Millennium Cohort Study (n = 14,376). Inverse-probability weighting was used to estimate confounder-adjusted population-average effects of centre and non-centre-based childcare (compared to parental care only) between ages 26-31 months on (age 3): internalising and externalising symptoms, pro-social behaviour, independence, emotional dysregulation, vocabulary, school readiness, and body mass index. To assess impacts on inequalities, controlled direct effects of low parental education and lone parenthood on all outcomes were estimated under two hypothetical scenarios: 1) universal take-up of centre-based childcare; and 2) parental care only. On average, non-centre based childcare improved vocabulary and centre-based care improved school readiness, with little evidence of other benefits. However, socio-economic inequalities were observed for all outcomes and were attenuated in scenario 1 (universal take-up). For example, inequalities in externalising symptoms (according to low parental education) were reduced from a confounder-adjusted standard deviation difference of 7.8 (95% confidence intervals: 6.7-8.8), to 1.7 (0.6-2.7). Inequalities by parental education in scenario 2 (parental care only) were wider than in scenario 1 for externalising symptoms (at 3.4; 2.4-4.4), and for emotional dysregulation and school readiness. Inequalities by lone parenthood, which were smaller, fell in scenario 1, and fell further in scenario 2. Universal access to centre-based pre-school care may alleviate inequalities, while restricted access (e.g. during lockdown for a pandemic such as Covid-19) may widen some inequalities in socioemotional and cognitive development.
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http://dx.doi.org/10.1016/j.ssmph.2021.100776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980060PMC
June 2021

Evaluation of an electronic consultation service for transgender care.

BMC Fam Pract 2021 Mar 20;22(1):55. Epub 2021 Mar 20.

C.T. Lamont Primary Health Care Research Centre, Bruyère Research Institute, Ottawa, ON, Canada.

Background: Access to transgender care in Canada is poor. Although primary care providers are ideally positioned to initiate care, many feel uncomfortable providing transgender care. This study aimed to explore the impact of an electronic consultation (eConsult) service between primary care providers and transgender care specialists on access to care and to explore the content of clinical questions that were asked.

Methods: This was a retrospective mixed methods analysis of 62 eConsults submitted between January 2017 and December 2018 by primary care providers to specialists in transgender care in a health region in eastern Ontario, Canada. A descriptive analysis was conducted to assess the average response time and the total time spent by the specialist for the eConsults. An inductive and deductive content analysis was carried out to identify common themes of clinical questions being asked to transgender specialists. A post-eConsult survey completed by primary care providers was assessed to gain insight into avoided face-to-face referrals and overall provider satisfaction.

Results: The median specialist response time was 1.2 days (range: 1 h to 5 days) and the average time spent by specialists per eConsult was 18 min (range: 10 to 40 min). The qualitative analysis identified six major themes: 1) interpretation/management of abnormal bloodwork, 2) change in management due to lack of desired effect/hormone levels not a target, 3) initiation of hormone therapy/initial work up, 4) management of adverse effects of hormone therapy, 5) transition related surgery counseling and post-op complications, and 6) management of patients with comorbidities. Approximately one-third of eConsults resulted in an avoided face-to-face referral and 95% of primary care providers rated the value of their eConsult as a 5 (excellent value) or 4.

Conclusions: This study demonstrated that a transgender eConsult service has potential to significantly improve access to care for transgender patients. Given the importance that timely access has on improving mental health and reducing suicide attempts, eConsult has the potential to make a substantial clinical impact on this population. Identified themes of eConsult questions provides insight into potential gaps in knowledge amongst primary care providers that could help inform future continuing education events.
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http://dx.doi.org/10.1186/s12875-021-01401-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980551PMC
March 2021

Predictors of COVID-19 vaccine hesitancy in the UK household longitudinal study.

Brain Behav Immun 2021 05 11;94:41-50. Epub 2021 Mar 11.

Understanding Society, Institute for Social and Economic Research, University of Essex, UK.

Vaccine hesitancy could undermine efforts to control COVID-19. We investigated the prevalence of COVID-19 vaccine hesitancy in the UK and identified vaccine hesitant subgroups. The 'Understanding Society' COVID-19 survey asked participants (n = 12,035) their likelihood of vaccine uptake and reason for hesitancy. Cross-sectional analysis assessed vaccine hesitancy prevalence and logistic regression calculated odds ratios. Overall vaccine hesitancy was low (18% unlikely/very unlikely). Vaccine hesitancy was higher in women (21.0% vs 14.7%), younger age groups (26.5% in 16-24 year olds vs 4.5% in 75 + ) and those with lower education levels (18.6% no qualifications vs 13.2% degree qualified). Vaccine hesitancy was high in Black (71.8%) and Pakistani/Bangladeshi (42.3%) ethnic groups. Odds ratios for vaccine hesitancy were 13.42 (95% CI:6.86, 26.24) in Black and 2.54 (95% CI:1.19, 5.44) in Pakistani/Bangladeshi groups (compared to White British/Irish) and 3.54 (95% CI:2.06, 6.09) for people with no qualifications versus degree. Urgent action to address hesitancy is needed for some but not all ethnic minority groups.
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http://dx.doi.org/10.1016/j.bbi.2021.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946541PMC
May 2021

Novel somatic mutations in UBA1 as a cause of VEXAS syndrome.

Blood 2021 Mar 9. Epub 2021 Mar 9.

University of Leeds, Leeds, United Kingdom.

Somatic mutations at methionine 41 (Met41) in UBA1, encoding the major E1 enzyme responsible for initiating ubiquitylation, were recently identified as the cause of a novel autoinflammatory disease, named VEXAS (Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic). We sought to determine the prevalence of UBA1 mutations in a UK cohort of patients matching the VEXAS clinical phenotype. We identified 10 new patients with somatic mutations in UBA1, but only 8 had altered p.Met41. A novel variant, c.167C>T; p.Ser56Phe was identified, which was present in myeloid, and not lymphoid lineages and led to preferential loss of the catalytic activity of cytoplasmic UBA1. An additional novel variant, c.118-1G>C was identified at the splice acceptor site of exon 3 leading to altered splicing in vitro. Bone marrow biopsies from two patients with a Met41 substitution and the novel splice site variant were consistent with previously reported features of VEXAS. The bone marrow of the patient with the p.Ser56Phe variant was less similar, likely driven by a distinct but overlapping disease mechanism. Our study therefore confirms somatic p.Met41 substitutions in UBA1 as a major cause of VEXAS syndrome and identifies two new disease causing mutations.
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http://dx.doi.org/10.1182/blood.2020010286DOI Listing
March 2021

SARS-CoV-2 and pediatric solid organ transplantation: Current knowns and unknowns.

Pediatr Transplant 2021 Mar 10:e13986. Epub 2021 Mar 10.

Department of Pediatrics, Infectious Diseases and Host Defense, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.

The COVID-19 pandemic has proven to be a challenge in regard to the clinical presentation, prevention, diagnosis, and management of SARS-CoV-2 infection among children who are candidates for and recipients of SOT. By providing scenarios and frequently asked questions encountered in routine clinical practice, this document provides expert opinion and summarizes the available data regarding the prevention, diagnosis, and management of SARS-CoV-2 infection among pediatric SOT candidates and recipients and highlights ongoing knowledge gaps requiring further study. Currently available data are still lacking in the pediatric SOT population, but data have emerged in both the adult SOT and general pediatric population regarding the approach to COVID-19. The document provides expert opinion regarding prevention, diagnosis, and management of SARS-CoV-2 infection among pediatric SOT candidates and recipients.
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http://dx.doi.org/10.1111/petr.13986DOI Listing
March 2021

Validation of the American Joint Committee on Cancer Eighth Edition Staging of Patients With Metastatic Cutaneous Melanoma Treated With Immune Checkpoint Inhibitors.

JAMA Netw Open 2021 Mar 1;4(3):e210980. Epub 2021 Mar 1.

Department of Radiation Oncology, University of Michigan, Ann Arbor.

Importance: Immune checkpoint inhibitors (ICIs) have transformed the survival of patients with metastatic melanoma. Patient prognosis is reflected by the American Joint Committee on Cancer (AJCC) staging system; however, it is unknown whether the metastatic (M) stage categories for cutaneous melanoma remain informative of prognosis in patients who have received ICIs.

Objectives: To evaluate the outcomes of patients with metastatic cutaneous melanoma based on the M stage category from the AJCC eighth edition and to determine whether these designations continue to inform the prognosis of patients who have received ICIs.

Design, Setting, And Participants: This cohort study included patients with metastatic cutaneous melanoma who were treated between August 2006 and August 2019 at the University of Michigan. The estimated median follow-up time was 35.5 months. Patient data were collected via the electronic medical record system. Critical findings were externally validated in a multicenter nationwide cohort of patients treated within the Veterans Affairs health care system. Data analysis was conducted from February 2020 to January 2021.

Exposures: All patients were treated with dual-agent concurrent ipilimumab and nivolumab followed by maintenance nivolumab or single-agent ipilimumab, nivolumab, or pembrolizumab therapy. Patients were staged using the AJCC eighth edition.

Main Outcomes And Measures: Univariable and multivariable analyses were used to assess the prognostic value of predefined clinicopathologic baseline factors on survival.

Results: In a discovery cohort of 357 patients (mean [SD] age, 62.6 [14.2] years; 254 [71.1%] men) with metastatic cutaneous melanoma treated with ICIs, the M category in the AJCC eighth edition showed limited prognostic stratification by both univariable and multivariable analyses. The presence of liver metastases and elevated levels of serum lactate dehydrogenase (LDH) offered superior prognostic separation compared with the M category (liver metastases: hazard ratio, 2.22; 95% CI, 1.48-3.33; P < .001; elevated serum LDH: hazard ratio, 1.73; 95% CI, 1.16-2.58; P = .007). An updated staging system based on these factors was externally validated in a cohort of 652 patients (mean [SD] age, 67.9 [11.6] years; 630 [96.6%] men), with patients without liver metastases or elevated LDH levels having the longest survival (median overall survival, 30.7 months).

Conclusions And Relevance: This study found that the AJCC eighth edition M category was poorly reflective of prognosis in patients receiving ICIs. Future staging systems could consider emphasizing the presence of liver metastases and elevated LDH levels. Additional studies are needed to confirm the importance of these and other prognostic biomarkers.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.0980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944385PMC
March 2021

The Indigenous primary health care and policy research network: Guiding innovation within primary health care with Indigenous peoples in Alberta.

Health Policy 2021 Feb 25. Epub 2021 Feb 25.

Department of Family Medicine, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive, NW, Calgary, AB T2N 4N1, Canada; O'Brien Institute for Public Health, University of Calgary, 3330 Hospital Drive, NW, Calgary, AB T2N 4N1, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive, NW, Calgary, AB T2N 4N1, Canada.

In 2015, the Truth and Reconciliation Commission of Canada released its Final Report with 94 Calls to Action, several of which called upon the health care sector to reform based on the principles of reconciliation. In the province of Alberta, Canada, numerous initiatives have arisen to address the health legacy Calls to Action, yet there is no formal mechanism to connect them all. As such, these initiatives have resulted in limited improvements overall. Recognizing the need for clear leadership, responsibility, and dedicated funding, stakeholders from across Alberta were convened in the Spring of 2019 for two full-day roundtable meetings to provide direction for a proposed Canadian Institutes of Health Research Network Environment for Indigenous Health Research that focused on primary health care and policy research. The findings from these roundtable meetings were synthesized and integrated into the foundational principles of the Indigenous Primary Health Care and Policy Research (IPHCPR) Network. The IPHCPR Network has envisioned a renewed and transformed primary health care system to achieve Indigenous health equity, aligned with principles and health legacy Calls to Action advocated by the Truth and Reconciliation Commission of Canada.
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http://dx.doi.org/10.1016/j.healthpol.2021.02.007DOI Listing
February 2021

Potential biases when observing increased mortality risk in association with smoking cessation among older adults.

Authors:
Michael J Green

Age Ageing 2021 Mar 2. Epub 2021 Mar 2.

MRC/CSO Social and Public Health Sciences Unit, University of Glasgow, 200 Renfield Street Glasgow G2 3AX, Glasgow, UK.

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http://dx.doi.org/10.1093/ageing/afab041DOI Listing
March 2021

Oxycodone/naloxone prolonged-release tablets in patients with moderate-to-severe, chronic cancer pain: Challenges in the context of hepatic impairment.

Asia Pac J Clin Oncol 2021 Mar 3. Epub 2021 Mar 3.

The University of Sheffield, Oncology, Western Bank, Sheffield, UK.

Opioids such as oxycodone are recommended in the management of moderate-to-severe, chronic cancer pain. All opioids can potentially cause constipation, which may be a significant barrier to their use. Multiple randomised clinical trials have shown that the use of naloxone as a peripherally acting mu-opioid receptor antagonist, in combination with oxycodone can prevent or reduce opioid-induced constipation while having equivalent analgesic efficacy to oxycodone alone. However, clinical experience has shown that unexpected events may occur in some patients when unrecognized liver impairment is present. We describe the underlying biological reasons and propose simple, but effective steps to avoid this unusual but potentially serious occurrence. In healthy individuals, naloxone undergoes extensive hepatic first pass metabolism resulting in low systemic bioavailability. However, in patients with hepatic impairment, porto-systemic shunting can increase systemic bioavailability of naloxone, potentially compromising the analgesic efficacy of oral naloxone-oxycodone combinations. This reduced first pass effect can occur in a range of settings that may not always be apparent to the treating clinician, including silent cirrhosis, non-cirrhotic portal hypertension and disruption of liver internal vasculature by metastases. Hepatic function test results correlate poorly with presence and extent of liver disease, and are not indicative of porto-systemic shunting. Presence of hepatic impairment should thus be considered when medication-related outcomes with oxycodone-naloxone combination are not as expected, even if liver function test results are normal.
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http://dx.doi.org/10.1111/ajco.13561DOI Listing
March 2021

BET proteolysis targeted chimera-based therapy of novel models of Richter Transformation-diffuse large B-cell lymphoma.

Leukemia 2021 Mar 2. Epub 2021 Mar 2.

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Richter Transformation (RT) develops in CLL as an aggressive, therapy-resistant, diffuse large B cell lymphoma (RT-DLBCL), commonly clonally-related (CLR) to the concomitant CLL. Lack of available pre-clinical human models has hampered the development of novel therapies for RT-DLBCL. Here, we report the profiles of genetic alterations, chromatin accessibility and active enhancers, gene-expressions and anti-lymphoma drug-sensitivity of three newly established, patient-derived, xenograft (PDX) models of RT-DLBCLs, including CLR and clonally-unrelated (CLUR) to concomitant CLL. The CLR and CLUR RT-DLBCL cells display active enhancers, higher single-cell RNA-Seq-determined mRNA, and protein expressions of IRF4, TCF4, and BCL2, as well as increased sensitivity to BET protein inhibitors. CRISPR knockout of IRF4 attenuated c-Myc levels and increased sensitivity to a BET protein inhibitor. Co-treatment with BET inhibitor or BET-PROTAC and ibrutinib or venetoclax exerted synergistic in vitro lethality in the RT-DLBCL cells. Finally, as compared to each agent alone, combination therapy with BET-PROTAC and venetoclax significantly reduced lymphoma burden and improved survival of immune-depleted mice engrafted with CLR-RT-DLBCL. These findings highlight a novel, potentially effective therapy for RT-DLBCL.
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http://dx.doi.org/10.1038/s41375-021-01181-wDOI Listing
March 2021

Sodium Fluoride-18 and Radium-223 Dichloride Uptake Colocalize in Osteoblastic Mouse Xenograft Tumors.

Cancer Biother Radiopharm 2021 Mar 25;36(2):133-142. Epub 2021 Feb 25.

Molecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Patients with osteoblastic bone metastases are candidates for radium-223 (RaCl) therapy and may undergo sodium fluoride-18 (F-NaF) positron emission tomography-computed tomography imaging to identify bone lesions. F-NaF has been shown to predict RaCl uptake, but intratumor distributions of these two agents remain unclear. In this study, the authors evaluate the spatial distribution and relative uptakes of F-NaF and RaCl in Hu09-H3 human osteosarcoma mouse xenograft tumors at macroscopic and microscopic levels to better quantify their correlation. F-NaF and RaCl were co-injected into Hu09-H3 xenograft tumor severe combined immunodeficient mice. Tumor content was determined from biodistributions and visualized by PET, single photon emission computed tomography, and CT imaging. Intratumor distributions were visualized by quantitative autoradiography of tumor tissue sections and compared to histology of the same or adjacent sections. F and Ra accumulated in proportional amounts in whole Hu09-H3 tumors ( = 0.82) and in microcalcified regions within these tumors ( = 0.87). Intratumor distributions of F and Ra were spatially congruent in these microcalcified regions. F-NaF and RaCl uptake are strongly correlated in heterogeneously distributed microcalcified regions of Hu09-H3 xenograft tumors, and thus, tumor accumulation of F is predictive of Ra accumulation. Hu09-H3 xenograft tumors appear to possess certain histopathological features found in patients with metastatic bone disease and may be useful in clarifying the relationship between administered Ra dose and therapeutic effect.
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http://dx.doi.org/10.1089/cbr.2020.4068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994428PMC
March 2021

Evaluation of the durability and use of long-lasting insecticidal nets in Nicaragua.

Malar J 2021 Feb 19;20(1):106. Epub 2021 Feb 19.

Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, USA.

Background: Vector control for malaria prevention relies most often on the use of insecticide-treated bed net (ITNs) and indoor residual spraying. Little is known about the longevity of long-lasting insecticidal nets (LLINs) in the Americas. The physical integrity and insecticide retention of LLINs over time were monitored after a bed net distribution campaign to assess community practices around LLIN care and use in Waspam, northeastern Nicaragua.

Methods: At least 30 nets were collected at 6, 12, 24, and 36 months post distribution. Physical integrity was measured by counting holes and classifying nets into categories (good, damaged, and too torn) depending on a proportionate hole index (pHI). Insecticide bioefficacy was assessed using cone bioassays, and insecticide content measured using a cyanopyrethroid field test (CFT).

Results: At 6 months, 87.3 % of LLINs were in good physical condition, while by 36 months this decreased to 20.6 %, with 38.2 % considered 'too torn.' The median pHI increased from 7 at the 6-month time point to 480.5 by 36 months. After 36 months of use, median mortality in cone bioassays was 2 % (range: 0-6 %) compared to 16 % (range: 2-70 %) at 6 months. There was a decrease in the level of deltamethrin detected on the surface of the LLINs with 100 % of tested LLINs tested at 12 months and 24 months crossing the threshold for being considered a failed net by CFT.

Conclusions: This first comprehensive analysis of LLIN durability in Central America revealed rapid loss of chemical bioefficacy and progressive physical damage over a 36-month period. Use of these findings to guide future LLIN interventions in malaria elimination settings in Nicaragua, and potentially elsewhere in the Americas, could help optimize the successful implementation of vector control strategies.
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http://dx.doi.org/10.1186/s12936-021-03604-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893764PMC
February 2021

Weighted-Support Vector Machine Learning Classifier of Circulating Cytokine Biomarkers to Predict Radiation-Induced Lung Fibrosis in Non-Small-Cell Lung Cancer Patients.

Front Oncol 2020 1;10:601979. Epub 2021 Feb 1.

Department of Clinical Oncology, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.

Background: Radiation-induced lung fibrosis (RILF) is an important late toxicity in patients with non-small-cell lung cancer (NSCLC) after radiotherapy (RT). Clinically significant RILF can impact quality of life and/or cause non-cancer related death. This study aimed to determine whether pre-treatment plasma cytokine levels have a significant effect on the risk of RILF and investigate the abilities of machine learning algorithms for risk prediction.

Methods: This is a secondary analysis of prospective studies from two academic cancer centers. The primary endpoint was grade≥2 (RILF2), classified according to a system consistent with the consensus recommendation of an expert panel of the AAPM task for normal tissue toxicity. Eligible patients must have at least 6 months' follow-up after radiotherapy commencement. Baseline levels of 30 cytokines, dosimetric, and clinical characteristics were analyzed. Support vector machine (SVM) algorithm was applied for model development. Data from one center was used for model training and development; and data of another center was applied as an independent external validation.

Results: There were 57 and 37 eligible patients in training and validation datasets, with 14 and 16.2% RILF2, respectively. Of the 30 plasma cytokines evaluated, SVM identified baseline circulating CCL4 as the most significant cytokine associated with RILF2 risk in both datasets ( = 0.003 and 0.07, for training and test sets, respectively). An SVM classifier predictive of RILF2 was generated in Cohort 1 with CCL4, mean lung dose (MLD) and chemotherapy as key model features. This classifier was validated in Cohort 2 with accuracy of 0.757 and area under the curve (AUC) of 0.855.

Conclusions: Using machine learning, this study constructed and validated a weighted-SVM classifier incorporating circulating CCL4 levels with significant dosimetric and clinical parameters which predicts RILF2 risk with a reasonable accuracy. Further study with larger sample size is needed to validate the role of CCL4, and this SVM classifier in RILF2.
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http://dx.doi.org/10.3389/fonc.2020.601979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883680PMC
February 2021

Social Cognitive Networks and Social Cognitive Performance Across Individuals With Schizophrenia Spectrum Disorders and Healthy Control Participants.

Biol Psychiatry Cogn Neurosci Neuroimaging 2020 Dec 5. Epub 2020 Dec 5.

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background: Schizophrenia spectrum disorders (SSDs) feature social cognitive deficits, although their neural basis remains unclear. Social cognitive performance may relate to neural circuit activation patterns more than to diagnosis, which would have important prognostic and therapeutic implications. The current study aimed to determine how functional connectivity within and between social cognitive networks relates to social cognitive performance across individuals with SSDs and healthy control participants.

Methods: Participants with SSDs (n = 164) and healthy control participants (n = 117) completed the Empathic Accuracy task during functional magnetic resonance imaging as well as lower-level (e.g., emotion recognition) and higher-level (e.g., theory of mind) social cognitive measures outside the scanner. Functional connectivity during the Empathic Accuracy task was analyzed using background connectivity and graph theory. Data-driven social cognitive networks were identified across participants. Regression analyses were used to examine network connectivity-performance relationships across individuals. Positive and negative within- and between-network connectivity strengths were also compared in poor versus good social cognitive performers and in SSD versus control groups.

Results: Three social cognitive networks were identified: motor resonance, affect sharing, and mentalizing. Regression and group-based analyses demonstrated reduced between-network negative connectivity, or segregation, and greater within- and between-network positive connectivity in worse social cognitive performers. There were no significant effects of diagnostic group on within- or between-network connectivity.

Conclusions: These findings suggest that the neural circuitry of social cognitive performance may exist dimensionally. Across participants, better social cognitive performance was associated with greater segregation between social cognitive networks, whereas poor versus good performers may compensate via hyperconnectivity within and between social cognitive networks.
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http://dx.doi.org/10.1016/j.bpsc.2020.11.014DOI Listing
December 2020

The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing.

Nat Cancer 2020 22;1:653-664. Epub 2020 Jun 22.

Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Cancer cells adapt their metabolic activities to support growth and proliferation. However, increased activity of metabolic enzymes is not usually considered an initiating event in the malignant process. Here, we investigate the possible role of the enzyme serine hydroxymethyltransferase-2 (SHMT2) in lymphoma initiation. localizes to the most frequent region of copy number gains at chromosome 12q14.1 in lymphoma. Elevated expression of cooperates with in lymphoma development; loss or inhibition of impairs lymphoma cell survival. SHMT2 catalyzes the conversion of serine to glycine and produces an activated one-carbon unit that can be used to support -adenosyl methionine synthesis. SHMT2 induces changes in DNA and histone methylation patterns leading to promoter silencing of previously uncharacterized mutational genes, such as and Together, our findings reveal that amplification of in cooperation with is sufficient in the initiation of lymphomagenesis through epigenetic tumor suppressor silencing.
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http://dx.doi.org/10.1038/s43018-020-0080-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872152PMC
June 2020

Risk factors for fellow eye treatment in protocol T.

Graefes Arch Clin Exp Ophthalmol 2021 Feb 10. Epub 2021 Feb 10.

Department of Ophthalmology, Boston University School of Medicine, 85 East Concord Street, 8th floor, Boston, MA, 02118, USA.

Purpose: To identify risk factors for fellow eye treatment of diabetic retinopathy with Vascular Endothelial Growth Factor (VEGF) injections during the Diabetic Retinopathy Clinical Research Network (DRCR.Net) Protocol T trial METHODS: In this post-hoc analysis of randomized clinical trial data, Cox regression analysis was performed at 52 and 104 weeks to determine risk factors for treatment in 360 fellow eyes. Survival analysis was performed to determine mean time to treatment based upon medication used.

Results: Of 360 fellow eyes, 142 (39.4%) required treatment between weeks 4 and 104. Risk factors predicting a lower likelihood of year 1 treatment included older subject age (Hazard Ratio [HR]=0.98, 95% CI 0.96-0.99; p = 0.02) and higher baseline study eye ETDRS score (HR=0.98, 95% CI 0.97-0.99, p = 0.04). Center-involving DME at baseline in the fellow eye was predictive of a higher treatment need at both 52 (HR=1.89, 95% CI 1.42-2.51, p < 0.0001) and 104 weeks (HR=2.68, 95% CI 1.75-4.11, p < 0.0001). Subjects treated in the study eye with aflibercept (HR=0.574, 95% CI 0.371-0.887, p = 0.013) and ranibizumab (HR=0.58, 95%CI 0.36-0.94, p = 0.03) were less likely to require first year fellow eye injection than subjects treated with bevacizumab although this difference was no longer significant at week 104 (aflibercept HR=0.77, 95% CI 0.52-1.16, p = 0.21; ranibizumab HR=0.66, 95% CI 0.43-1.00, p = 0.05). Mean time to treatment was significantly shorter in the bevacizumab group (bevacizumab 25.83 weeks, aflibercept 38.75 weeks, ranibizumab 34.70 weeks (p=0.012)).

Conclusion: Bilateral treatment with intravitreal anti-VEGF injections was common during the DRCR.net Protocol T. Medication choice may impact the risk of fellow eye treatment.
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http://dx.doi.org/10.1007/s00417-021-05108-0DOI Listing
February 2021

Shifts in office and virtual primary care during the early COVID-19 pandemic in Ontario, Canada.

CMAJ 2021 02;193(6):E200-E210

ICES Central (Glazier, Wu, Kopp, Kiran); Primary Care and Health Systems (Glazier, Kiran, Kopp); St. Michael's Hospital Centre for Urban Health Solutions (Glazier, Kiran), Toronto, Ont.; Department of Family Medicine, and Health Services and Policy Research Institute (Green), Queen's University, Kingston, Ont.; Health Services and Policy Research Institute, Queen's University, and ICES Queen's (Frymire), Kingston, Ont.; Department of Family and Community Medicine (Glazier, Kiran), St. Michael's Hospital, University of Toronto, Toronto, Ont.

Background: Globally, primary care changed dramatically as a result of the coronavirus disease 2019 (COVID-19) pandemic. We aimed to understand the degree to which office and virtual primary care changed, and for which patients and physicians, during the initial months of the pandemic in Ontario, Canada.

Methods: This population-based study compared comprehensive, linked primary care physician billing data from Jan. 1 to July 28, 2020, with the same period in 2019. We identified Ontario residents with at least 1 office or virtual (telephone or video) visit during the study period. We compared trends in total physician visits, office visits and virtual visits before COVID-19 with trends after pandemic-related public health measures changed the delivery of care, according to various patient and physician characteristics. We used interrupted time series analysis to compare trends in the early and later halves of the COVID-19 period.

Results: Compared with 2019, total primary care visits between March and July 2020 decreased by 28.0%, from 7.66 to 5.51 per 1000 people/day. The smallest declines were among patients with the highest expected health care use (8.3%), those who could not be attributed to a primary care physician (10.2%), and older adults (19.1%). In contrast, total visits in rural areas increased by 6.4%. Office visits declined by 79.1% and virtual care increased 56-fold, comprising 71.1% of primary care physician visits. The lowest uptake of virtual care was among children (57.6%), rural residents (60.6%) and physicians with panels of ≥ 2500 patients (66.0%).

Interpretation: Primary care in Ontario saw large shifts from office to virtual care over the first 4 months of the COVID-19 pandemic. Total visits declined least among those with higher health care needs. The determinants and consequences of these major shifts in care require further study.
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http://dx.doi.org/10.1503/cmaj.202303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954541PMC
February 2021

Can centre-based childcare buffer against the negative effects of family adversity on child socio-emotional wellbeing?

Eur J Public Health 2021 Feb 7. Epub 2021 Feb 7.

MRC/CSO Social and Public Health Sciences Unit, University of Glasgow, Glasgow, UK.

Background: Different configurations of family adversity affect children's socio-emotional development differently; however, we lack knowledge of moderators amenable to policy intervention. This study explored whether early childhood centre-based childcare moderated the impact of family adversity configurations on socio-emotional development.

Methods: Data were from the Growing Up in Scotland first birth cohort, born 2004-05. Latent class analysis of 19 early childhood family adversity indicators identified four classes: 'Low Risk' (68%), 'Poor Maternal Health' (16.5%), 'Economic Hardship' (10.0%) and 'Multiple Adversities' (5.5%). Latent growth models of externalizing and internalizing symptom trajectories (age 46-152 months, n = 3561) by family adversity controlled for confounding. Moderation by centre-based childcare use was examined through stratification.

Results: Compared to 'Low Risk', high-risk classes had more externalizing and internalizing symptoms and internalizing symptoms increased at a faster rate, with 'Multiple Adversities' faring worst. The effects of 'Economic Hardship' on change in externalizing symptoms over time varied by childcare (P = 0.035): relative to the Low Risk group, symptoms increased (+0.04 points/year) among those not using childcare, and decreased (-0.09 points/year) among those who did. The effect of 'Multiple Adversities' on internalizing symptoms also varied (P = 0.034): +0.12 without centre-based childcare; +0.33 with centre-based childcare (patterns were similar for externalizing symptoms but with wide confidence intervals). No moderation was found by 'Poor Maternal Health'.

Conclusions: Centre-based childcare may alleviate disadvantages in socio-emotional wellbeing for children experiencing mainly economic hardship, but may exacerbate them for those experiencing multiple adversities. A better understanding of how early years' services can support families with complex needs is required.
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http://dx.doi.org/10.1093/eurpub/ckab006DOI Listing
February 2021

Restriction Enzymes.

Cold Spring Harb Protoc 2021 Apr 1;2021(4):pdb.top101360. Epub 2021 Apr 1.

Restriction enzymes provided the foundation on which molecular cloning was built, and they remain as essential tools in current recombinant DNA technology. The three classes of restriction enzymes and their features are introduced here.
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http://dx.doi.org/10.1101/pdb.top101360DOI Listing
April 2021

Prognostic Impact of Corticosteroids on Efficacy of Chimeric Antigen Receptor T-cell Therapy in Large B-cell Lymphoma.

Blood 2021 Feb 3. Epub 2021 Feb 3.

The University of Texas MD Anderson Cancer Center, Houston, Texas, United States.

Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may impact clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy-associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803 mg) and the median duration of corticosteroid treatment was 9 days (range 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% CI 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible, while managing CAR T-cell therapy-associated toxicities.
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http://dx.doi.org/10.1182/blood.2020008865DOI Listing
February 2021

Radiolabeling of Subtracted cDNA Probes by Random Oligonucleotide Extension.

Cold Spring Harb Protoc 2021 02 1;2021(2). Epub 2021 Feb 1.

In this procedure, synthesis of cDNA is performed in the presence of saturating concentrations of all four dNTPs and trace amounts of a single radiolabeled dNTP. After subtraction hybridization, the enriched single-stranded cDNA is radiolabeled to high specific activity in a second synthetic reaction by extension of random oligonucleotide primers using the Klenow fragment of DNA Pol I. Because the concentrations of dNTP in the first reaction are nonlimiting, both the amounts and size of cDNA generated are greater than those achieved in standard labeling protocols. The subtractive hybridization step can therefore be performed with higher efficiency. Because the resulting population of cDNA is not vulnerable to radiolytic cleavage, it can be stored indefinitely and radiolabeled to higher specific activity when needed. The protocol works best when the cDNA synthesized in the initial synthetic reaction is full length or close to it. For this reason, synthesis of cDNAs is primed by oligo(dT) rather than random hexanucleotide primers. In contrast, the subsequent radiolabeling reaction is primed by random oligonucleotides, yielding shorter DNA products whose size is ideal for hybridization.
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http://dx.doi.org/10.1101/pdb.prot100644DOI Listing
February 2021