Publications by authors named "Matthew J Reynolds"

12 Publications

  • Page 1 of 1

Coping Strategies in Patients with Acute Myeloid Leukemia.

Blood Adv 2021 Nov 12. Epub 2021 Nov 12.

Harvard Medical School, United States.

Patients diagnosed with acute myeloid leukemia (AML) face sudden-onset life-threatening disease that requires intensive treatments. Although their early disease trajectory is characterized by significant, toxic side effects, there is limited data describing coping strategies among patients with AML and how these inform patient-reported outcomes. We used cross-sectional secondary data analyses to describe coping in 160 patients with newly diagnosed high-risk AML. We used the Brief COPE, Hospital Anxiety and Depression Scale, PTSD Checklist-Civilian Version, and Functional Assessment of Cancer Therapy-Leukemia at time of AML diagnosis to measure coping strategies, psychological distress and quality of life (QOL), respectively. We used the median split method for distribution of coping domains, and multivariate regression models to assess the relationship between coping and patient-reported outcomes. Participants (median age=64.4 years) were mostly non-Hispanic White (86.3%), male (60.0%), and married (73.8%). Most (51.9%) had high utilization of approach-oriented coping strategies whereas 38.8% had high utilization of avoidant coping strategies. At time of diagnosis, use of approach-oriented coping was associated with less psychological distress (anxiety: β=-0.262, p=0.002; depression symptoms β=-0.311, p<0.001; PTSD symptoms: β=-0.596, p=0.006) and better QOL (β=1.491, p=0.003). Use of avoidant coping was associated with more psychological distress (anxiety: β=0.884, p<0.001; depression symptoms: β=0.697, p<0.001; PTSD symptoms: β=3.048, p<0.001) and worse QOL (β=-5.696, p<0.001). Patients with high-risk AML utilize various approach-oriented and avoidant coping strategies at time of diagnosis. Use of approach-oriented coping strategies was associated with less psychological distress and better QOL, suggesting a possible target for supportive oncology interventions.
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http://dx.doi.org/10.1182/bloodadvances.2021005845DOI Listing
November 2021

End-of-Life Care for Older Adults with Aggressive Non-Hodgkin Lymphoma.

J Palliat Med 2021 Nov 1. Epub 2021 Nov 1.

Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.

Aggressive non-Hodgkin lymphoma (NHL) commonly affects older adults and is often treated with intensive therapies. Receipt of intensive therapies and absence of a clear transition between the curative and palliative phases of treatment yield prognostic uncertainty and risk for poor end-of-life (EOL) outcomes. However, data regarding the EOL outcomes of this population are lacking. We conducted a retrospective analysis of adults ≥65 years with aggressive NHL treated with systemic therapy at Massachusetts General Hospital from April 2000 to July 2020 who subsequently died. We abstracted patient and clinical characteristics and EOL outcomes from the medical record. Using multivariable logistic regression, we examined factors associated with hospitalization within 30 days of death and hospice utilization. Among 91 patients (median age = 75 years; 37.4% female), 70.3% (64/91) were hospitalized, 34.1% (31/91) received systemic therapy, and 23.3% (21/90) had an intensive care unit admission within 30 days of death. The rates of palliative care consultation and hospice utilization were 47.7% (42/88) and 39.8% (35/88), respectively. More than half of patients (51.6%, 47/91) died in a hospital or health care facility. In multivariable analysis, elevated lactic acid dehydrogenase was associated with risk of hospitalization within 30 days of death (odds ratio [OR] 3.61,  = 0.014). Palliative care consultation (OR 4.45,  = 0.005) was associated with a greater likelihood of hospice utilization, whereas hypoalbuminemia (OR 0.29,  = 0.026) was associated with a lower likelihood of hospice utilization. Older adults with aggressive NHL often experience high health care utilization and infrequently utilize hospice care at the EOL. Our findings underscore the need for interventions to optimize the quality of EOL care for this population.
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http://dx.doi.org/10.1089/jpm.2021.0228DOI Listing
November 2021

Association of Social Support With Overall Survival and Healthcare Utilization in Patients With Aggressive Hematologic Malignancies.

J Natl Compr Canc Netw 2021 Oct 15:1-7. Epub 2021 Oct 15.

1Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital.

Background: Social support plays a crucial role for patients with aggressive hematologic malignancies as they navigate their illness course. The aim of this study was to examine associations of social support with overall survival (OS) and healthcare utilization in this population.

Methods: A cross-sectional secondary analysis was conducted using data from a prospective longitudinal cohort study of 251 hospitalized patients with aggressive hematologic malignancies at Massachusetts General Hospital from 2014 through 2017. Natural Language Processing (NLP) was used to identify the extent of patients' social support (limited vs adequate as defined by NLP-aided chart review of the electronic health record). Multivariable regression models were used to examine associations of social support with (1) OS, (2) death or readmission within 90 days of discharge from index hospitalization, (3) time to readmission within 90 days, and (4) index hospitalization length of stay.

Results: Patients had a median age of 64 years (range, 19-93 years), and most were White (89.6%), male (68.9%), and married (65.3%). A plurality of patients had leukemia (42.2%) followed by lymphoma (37.9%) and myelodysplastic syndrome/myeloproliferative neoplasm (19.9%). Using NLP, we identified that 8.8% (n=22) of patients had limited social support. In multivariable analyses, limited social support was associated with worse OS (hazard ratio, 2.00; P=.042) and a higher likelihood of death or readmission within 90 days of discharge (odds ratio, 3.11; P=.043), but not with time to readmission within 90 days or with index hospitalization length of stay.

Conclusions: In this cohort of hospitalized patients with aggressive hematologic malignancies, we found associations of limited social support with lower OS and a higher likelihood of death or readmission within 90 days of hospital discharge. These findings underscore the utility of NLP for evaluating the extent of social support and the need for larger studies evaluating social support in patients with aggressive hematologic malignancies.
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http://dx.doi.org/10.6004/jnccn.2021.7033DOI Listing
October 2021

Distress in a Pandemic: Association of the Coronavirus Disease-2019 Pandemic with Distress and Quality of Life in Hematopoietic Stem Cell Transplantation.

Transplant Cell Ther 2021 Sep 15. Epub 2021 Sep 15.

Harvard Medical School, Boston, Massachusetts; Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital, Boston, Massachusetts.

The global coronavirus disease 2019 (COVID-19) pandemic has drastically disrupted cancer care, potentially exacerbating patients' distress levels. Patients undergoing hematopoietic stem cell transplantation (HSCT) may be especially vulnerable to this pandemic stress. However, the associations of the COVID-19 pandemic with distress, fatigue, and quality of life (QoL) are not well understood in this population. In a cross-sectional analysis of data from 205 patients undergoing HSCT enrolled in a supportive care trial, we compared baseline pre-HSCT distress symptoms (depression, anxiety, and posttraumatic stress disorder [PTSD]), fatigue, and QoL between enrollees before (ie, March 2019-January 2020) and during (ie, March 2020-January 2021) the COVID-19 pandemic. We used linear regression models adjusting for sociodemographics and cancer diagnosis to examine the associations between enrollment period and patient-reported outcomes. We used semistructured qualitative interviews in 20 allogeneic HSCT recipients who were ≥3-months post-HSCT to understand the impact of the COVID-19 pandemic on their recovery post-HSCT. One hundred twenty-four participants enrolled before COVID-19, and 81 participants enrolled during the pandemic. The 2 cohorts had similar baseline demographics and disease risk factors. In multivariate regression models, enrollment during COVID-19 was not associated with pre-HSCT symptoms of depression, anxiety, PTSD, fatigue, or QoL impairment. COVID-19-era participants reported themes of negative (eg, increased isolation) and positive (eg, engagement with meaningful activities) implications of the pandemic on HSCT recovery. We found no differences in pre-HSCT distress, fatigue, or QoL in patients undergoing HSCT before or during the COVID-19 pandemic; however, patients in early recovery post-HSCT report both negative and positive implications of the COVID-19 pandemic in their lives.
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http://dx.doi.org/10.1016/j.jtct.2021.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442257PMC
September 2021

Clinical Outcomes, Treatment Toxicity, and Health Care Utilization in Older Adults with Aggressive Non-Hodgkin Lymphoma.

Oncologist 2021 Nov 12;26(11):965-973. Epub 2021 Aug 12.

Division of Hematology & Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.

Background: Although balancing treatment efficacy with risks of complications is critical for older adults with aggressive non-Hodgkin lymphoma (NHL), few studies have described these patients' clinical outcomes, rates of toxicities, and health care utilization.

Methods: We conducted a retrospective analysis of adults ≥65 years diagnosed with aggressive NHL and receiving systemic therapy at Massachusetts General Hospital from April 2000 to July 2020. We abstracted patient characteristics, clinical outcomes, treatment toxicity, unplanned hospitalizations, and intensive care unit (ICU) admissions within 6 months of treatment initiation from the medical record. Using multivariable logistic regression, we examined factors associated with rates of grade 3+ nonhematologic toxicity and unplanned hospitalization.

Results: Among 295 patients (median age, 73 years; 39.0% female), 5-year overall survival (OS) was 74.2%. Five-year OS by age group (65-69, 70-74, 75-79, and 80+ years) was 82.2%, 72.0%, 73.6%, and 66.4%, respectively. Overall, 42.4% experienced grade 3+ toxicity, with 8.1% experiencing grades 4-5. The rates of unplanned hospitalization and ICU admission were 41.0% and 6.1%, respectively. In multivariable analysis, hypoalbuminemia (odds ratio [OR], 4.29; p < .001) and high comorbidity score (OR, 4.22; p < .001) were associated with likelihood of grade 3+ toxicity. Hypoalbuminemia (OR, 2.83; p = .003), high comorbidity score (OR, 3.93; p = .001), and receipt of EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin; OR, 5.45; p = .012) were associated with likelihood of unplanned hospitalization.

Conclusions: The majority of older adults receiving upfront therapy for aggressive NHL survive beyond 5 years, yet nearly half experience substantial treatment toxicities and unplanned hospitalizations. Our findings underscore the need for supportive care interventions to enhance the care experience of this population.

Implications For Practice: The results of this study highlight the potential benefits of intensive chemoimmunotherapy for the majority of older adults with aggressive non-Hodgkin lymphoma, even at advanced ages. Nearly half of older adults experienced substantial treatment toxicities and unplanned hospitalizations, emphasizing the unmet need for supportive care interventions in this population. The present study also identified hypoalbuminemia and patient comorbidity score as factors associated with grade 3+ nonhematologic toxicity and unplanned hospitalization. These findings may guide the development and implementation of targeted supportive care interventions in high-risk older adults with aggressive non-Hodgkin lymphoma.
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http://dx.doi.org/10.1002/onco.13915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571763PMC
November 2021

Palliative care for patients undergoing stem cell transplant: intervention components and supportive care measures.

Bone Marrow Transplant 2021 08 6;56(8):1971-1977. Epub 2021 Apr 6.

Massachusetts General Hospital, Boston, MA, USA.

An inpatient palliative care intervention during HCT led to improvement in patient QOL and mood. We sought to describe components of the intervention, investigate differences in supportive care practices by treatment arm, and explore whether these differences mediated the impact of the intervention on patient QOL and mood. We conducted a secondary analysis of a randomized trial investigating inpatient palliative care integrated with transplant care versus standard transplant care for HCT recipients. Palliative care clinicians completed weekly surveys to describe topics addressed during visits. We extracted use of supportive care medications from the medical record. Participants completed QOL and mood assessments at baseline and two weeks post-HCT. Causal mediation assessed whether differences in supportive care practices mediated the impact of the intervention on patient-reported outcomes. A total of 160 HCT recipients participated. Palliative care visits most frequently focused on managing symptoms and coping with HCT. Patients randomized to the intervention were more likely to use Patient-Controlled Analgesia (PCA) (32.1% vs. 15.2%, p = 0.02) and atypical antipsychotics (35.8% vs. 17.7%, p = 0.01). Neither PCA nor atypical antipsychotics mediated the effect of the intervention on patient-reported outcomes. Future work to explore mechanisms by which the palliative care intervention improves QOL and mood is needed.
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http://dx.doi.org/10.1038/s41409-021-01281-2DOI Listing
August 2021

Association Between Baseline Patient-Reported Outcomes and Complications of Hematopoietic Stem Cell Transplantation.

Transplant Cell Ther 2021 06 25;27(6):496.e1-496.e5. Epub 2021 Feb 25.

Department of Medicine, Division of Hematology & Oncology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston Massachusetts.

Hematopoietic cell transplantation (HCT) is a potentially curative therapy for hematologic malignancies, but it often results in significant toxicities and impaired quality of life (QOL). Although the value of patient-reported outcomes (PROs) is increasingly recognized in HCT, data are limited regarding the relationship between PROs and HCT complications. We conducted a secondary data analysis of 250 patients who were hospitalized for autologous or allogeneic HCT at Massachusetts General Hospital from 2011 through 2016. We assessed QOL (Functional Assessment of Cancer Therapy-General), mood (Hospital Anxiety and Depression Scale), and fatigue (FACT-Fatigue) at baseline. We abstracted from the Electronic Health Record (1) hospitalization during the first 100 days after HCT, (2) days alive and out of the hospital in the first 100 days after HCT, and (3) cumulative incidence of acute graft-versus-host disease (GVHD) among allogeneic HCT recipients. We assessed the association of baseline PROs with HCT complications using multivariable models adjusting for patient and transplant characteristics. Overall, 44.4% (111/250) of patients underwent an autologous HCT, 25.2% (63/250) received a myeloablative allogeneic HCT, and 30.4% (76/250) underwent a reduced-intensity allogeneic HCT. In multivariable logistic regression, higher anxiety (odds ratio [OR] = 1.14, P = .004) was associated with higher likelihood of rehospitalization within 100 days after HCT. In multivariable Poisson regression, lower fatigue (β = 0.003, P = .015) was associated with increased days alive and out of the hospital in the first 100 days post-HCT. In multivariable logistic regression, lower baseline QOL (OR = 0.97, P = .034), higher fatigue (OR = 0.95, P = .004), and higher depression (OR = 1.15, P = .020) were associated with increased likelihood of acute GVHD. Baseline PROs are associated with health care utilization after HCT and risk of acute GVHD in allogeneic HCT recipients. These findings underscore the potential utility of pretransplantation PROs as important prognostic factors for HCT.
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http://dx.doi.org/10.1016/j.jtct.2021.02.029DOI Listing
June 2021

Clinical Outcomes of Patients Hospitalized with Coronavirus Disease 2019 (COVID-19) in Boston.

J Gen Intern Med 2021 05 24;36(5):1285-1291. Epub 2021 Feb 24.

Department of Hematology Oncology, Massachusetts General Hospital, Boston, MA, USA.

Background: Outcomes of hospitalized patients with COVID-19 have been described in health systems overwhelmed with a surge of cases. However, studies examining outcomes of patients admitted to hospitals not in crisis are lacking.

Objective: To describe clinical characteristic and outcomes of all patients with COVID-19 who are admitted to hospitals not in crisis, and factors associated with mortality in this population.

Design: A retrospective analysis PARTICIPANTS: In total, 470 consecutive patients with COVID-19 requiring hospitalization in one health system in Boston from January 1, 2020 to April 15, 2020.

Main Measures: We collected clinical outcomes during hospitalization including intensive care unit (ICU) admission, receipt of mechanical ventilation, and vasopressors. We utilized multivariable logistic regression models to examine factors associated with mortality.

Key Results: A total of 470 patients (median age 66 [range 23-98], 54.0% male) were included. The most common comorbidities were diabetes (38.5%, 181/470) and obesity (41.3%, 194/470). On admission, 41.9% (197/470) of patients were febrile and 60.6% (285/470) required supplemental oxygen. During hospitalization, 37.9% (178/470) were admitted to the ICU, 33.6% (158/470) received mechanical ventilation, 29.4% (138/470) received vasopressors, 16.4% (77/470) reported limitations on their desire for life-sustaining therapies such as intubation and cardiopulmonary resuscitation, and 25.1% (118/470) died. Among those admitted to the ICU (N=178), the median number of days on the ventilator was 10 days (IQR 1-29), and 58.4% (104/178) were discharged alive. Older age (OR=1.04, P<0.001), male sex (OR=2.14, P=0.007), higher comorbidities (OR=1.20, P=0.001), higher lactate dehydrogenase on admission (2nd tertile: OR=4.07, P<0.001; 3rd tertile: OR=8.04, P<0.001), and the need for supplemental oxygen on admission (OR=2.17, P=0.014) were all associated with higher mortality.

Conclusions: The majority of hospitalized patients with COVID-19 and those who received mechanical ventilation survived. These data highlight the need to examine public health and system factors that contribute to improved outcomes for this population.
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http://dx.doi.org/10.1007/s11606-021-06622-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904295PMC
May 2021

Single-molecule and in silico dissection of the interaction between Polycomb repressive complex 2 and chromatin.

Proc Natl Acad Sci U S A 2020 12 18;117(48):30465-30475. Epub 2020 Nov 18.

Laboratory of Nanoscale Biophysics and Biochemistry, The Rockefeller University, New York, NY 10065;

Polycomb repressive complex 2 (PRC2) installs and spreads repressive histone methylation marks on eukaryotic chromosomes. Because of the key roles that PRC2 plays in development and disease, how this epigenetic machinery interacts with DNA and nucleosomes is of major interest. Nonetheless, the mechanism by which PRC2 engages with native-like chromatin remains incompletely understood. In this work, we employ single-molecule force spectroscopy and molecular dynamics simulations to dissect the behavior of PRC2 on polynucleosome arrays. Our results reveal an unexpectedly diverse repertoire of PRC2 binding configurations on chromatin. Besides reproducing known binding modes in which PRC2 interacts with bare DNA, mononucleosomes, and adjacent nucleosome pairs, our data also provide direct evidence that PRC2 can bridge pairs of distal nucleosomes. In particular, the "1-3" bridging mode, in which PRC2 engages two nucleosomes separated by one spacer nucleosome, is a preferred low-energy configuration. Moreover, we show that the distribution and stability of different PRC2-chromatin interaction modes are modulated by accessory subunits, oncogenic histone mutations, and the methylation state of chromatin. Overall, these findings have implications for the mechanism by which PRC2 spreads histone modifications and compacts chromatin. The experimental and computational platforms developed here provide a framework for understanding the molecular basis of epigenetic maintenance mediated by Polycomb-group proteins.
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http://dx.doi.org/10.1073/pnas.2003395117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720148PMC
December 2020

Molecular mechanism for direct actin force-sensing by α-catenin.

Elife 2020 09 24;9. Epub 2020 Sep 24.

Laboratory of Structural Biophysics and Mechanobiology, The Rockefeller University, New York, United States.

The actin cytoskeleton mediates mechanical coupling between cells and their tissue microenvironments. The architecture and composition of actin networks are modulated by force; however, it is unclear how interactions between actin filaments (F-actin) and associated proteins are mechanically regulated. Here we employ both optical trapping and biochemical reconstitution with myosin motor proteins to show single piconewton forces applied solely to F-actin enhance binding by the human version of the essential cell-cell adhesion protein αE-catenin but not its homolog vinculin. Cryo-electron microscopy structures of both proteins bound to F-actin reveal unique rearrangements that facilitate their flexible C-termini refolding to engage distinct interfaces. Truncating α-catenin's C-terminus eliminates force-activated F-actin binding, and addition of this motif to vinculin confers force-activated binding, demonstrating that α-catenin's C-terminus is a modular detector of F-actin tension. Our studies establish that piconewton force on F-actin can enhance partner binding, which we propose mechanically regulates cellular adhesion through α-catenin.
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http://dx.doi.org/10.7554/eLife.62514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588232PMC
September 2020

The Emergence of the Tobacco 21 Movement From Needham, Massachusetts, to Throughout the United States (2003-2019).

Am J Public Health 2019 11 19;109(11):1540-1547. Epub 2019 Sep 19.

At the time of the writing, Matthew J. Reynolds was an undergraduate student in the Department of Molecular and Cellular Biology at Harvard College, Cambridge, MA. Robert Crane is with The Ohio State University Wexner Medical Center, Columbus. Jonathan P. Winickoff is with Massachusetts General Hospital for Children and Harvard Medical School, Boston.

In February 2003, Needham, Massachusetts, became the first town in the nation to raise the minimum legal sales age for tobacco and nicotine products to 21 years (Tobacco 21). This legislation marked a dramatic departure from existing state and federal laws, which generally set the minimum sales age at 18 years. The Needham law significantly preceded and ultimately heralded the emergence of a nationwide movement to raise such sales age. As of May 2019, 14 states and more than 450 cities and counties have passed legislation raising the minimum legal sales age for tobacco and nicotine products to 21 years, covering more than 30% of the United States' population. The National Academy of Medicine projects that this policy will lower tobacco use rates, particularly among adolescents, and save a substantial number of lives. This narration of the process that led to Needham's passing of Tobacco 21 legislation and to the growth and spread of the Tobacco 21 movement highlights the significant role of public health advocacy and policy in the control of tobacco, the leading preventable cause of disease and death in the United States. ( 2019;109:1540-1547. doi: 10.2105/AJPH. 2019.305209).
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http://dx.doi.org/10.2105/AJPH.2019.305209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775922PMC
November 2019

The Developmental Process of the Growing Motile Ciliary Tip Region.

Sci Rep 2018 05 22;8(1):7977. Epub 2018 May 22.

Wadsworth Center, New York State Department of Health, Albany, NY, 12201, USA.

Eukaryotic motile cilia/flagella play vital roles in various physiological processes in mammals and some protists. Defects in cilia formation underlie multiple human disorders, known as ciliopathies. The detailed processes of cilia growth and development are still far from clear despite extensive studies. In this study, we characterized the process of cilium formation (ciliogenesis) by investigating the newly developed motile cilia of deciliated protists using complementary techniques in electron microscopy and image analysis. Our results demonstrated that the distal tip region of motile cilia exhibit progressive morphological changes as cilia develop. This developmental process is time-dependent and continues after growing cilia reach their full lengths. The structural analysis of growing ciliary tips revealed that B-tubules of axonemal microtubule doublets terminate far away from the tip end, which is led by the flagellar tip complex (FTC), demonstrating that the FTC might not directly mediate the fast turnover of intraflagellar transport (IFT).
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http://dx.doi.org/10.1038/s41598-018-26111-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964098PMC
May 2018
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