Snapshot of Science for May 2022

Welcome to our Snapshot of Science for May 2022.

Here's a quick look at some recent publications, press releases and stories about the Mass General Research Institute community.

In this issue we highlight:

34 new studies published in high-impact journals, along with 24 summaries submitted by the research teams
10 new research-related press releases from the Mass General Public Affairs office
5 posts from the Mass General Research Institute blog

Publications

Medication for Alcohol Use Disorder Significantly Lowers Risk of ALD
Incidence and Progression of Alcohol-associated Liver Disease After Medical Therapy for Alcohol Use Disorder
Vannier AGL, Shay JES, Fomin V, Patel SJ, Schaefer E, Goodman RP, Luther J
Published in JAMA Network Open on May 20, 2022 | *Summary available

High Resolution Assessment of Blood Vessels and Oxygen Levels in Tumors
Multiphoton Phosphorescence Quenching Microscopy Reveals Kinetics of Tumor Oxygenation During Antiangiogenesis and Angiotensin Signaling Inhibition
Martin JD, Lanning RM, Chauhan VP, Martin MR, Mousa AS [et al.], Jain RK
Published in Clinical Cancer Research on May 18, 2022 | *Summary available

Both Rare and Common Genetic Variants Contribute to HCM Risk
Rare and Common Genetic Variation Underlying the Risk of Hypertrophic Cardiomyopathy in a National Biobank
Biddinger KJ, Jurgens SJ, Maamari D, Gaziano L, Choi SH [et al.], Aragam KG
Published in JAMA Cardiology on May 18, 2022 | *Summary available

Use of Antenatal Steroids for Neonatal Respiratory Complications
U.S. Incidence of Late-Preterm Steroid Use and Associated Neonatal Respiratory Morbidity After Publication of the Antenatal Late Preterm Steroids Trial, 2015-2017
Clapp MA, Melamed A, Freret TS, James KE, Gyamfi-Bannerman C, Kaimal AJ
Published in JAMA Network Open on May 18, 2022 | *Summary available

The BCL2 Inhibitor Venetoclax in Patients With ER-positive Breast Tumors
VERONICA: Randomized Phase 2 Study of Fulvestrant and Venetoclax in ER-positive Metastatic Breast Cancer Post-CDK4/6 Inhibitors—Efficacy, Safety, Biomarker Results
Lindeman GJ, Fernando TM, Bowen R, Jerzak KJ, Song X [et al.], Bardia A
Published in Clinical Cancer Research on May 18, 2022 | *Summary available

Medication for Psychiatric Disorders in Childhood Appear to Reduce Later Risk of Substance Use Disorder
The Impact of Pharmacotherapy of Childhood-onset Psychiatric Disorders on the Development of Substance Use Disorders
Wilens TE, Woodward DW, Ko JD, Berger AF, Burke C, Yule AM
Published in Journal of Child and Adolescent Psychopharmacology on May 17, 2022 | *Summary available | Press Release

Clinical Decision Support Software Platform to Reduce Medication Errors
Usability of a Perioperative Medication-related Clinical Decision Support Software Application: A Randomized Controlled Trial
Nanji KC, Garabedian PM, Langlieb ME, Rui A, Tabayoyong LL [et al.], Bates DW
Published in Journal of the American Medical Informatics Association (JAMIA) on May 16, 2022 | *Summary available | Press Release

Updated PSA Screening Guidelines Could Reduce Prostate Cancer Mortality Rates
Association of the USPSTF Grade D Recommendation Against Prostate-Specific Antigen Screening With Prostate Cancer-specific Mortality
Burgess L, Aldrighetti CM, Ghosh A, Niemierko A, Chino F [et al.], Kamran SC
Published in JAMA Network Open on May 16, 2022 | *Summary available

A New Strategy for Fluorescence-guided Surgery
Topical pH Sensing NIR Fluorophores for Intraoperative Imaging and Surgery of Disseminated Ovarian Cancer
Yokomizo S, Henary M, Buabeng ER, Fukuda T, Monaco H [et al.], Choi HS
Published in Advanced Science on May 14, 2022 | *Summary available

A Novel Microgel That Supports Graft Survival After Transplantation
FasL Microgels Induce Immune Acceptance of Islet Allografts in Nonhuman Primates
Lei J, Coronel MM, Yolcu ES, Deng H, Grimany-Nuno O [et al.], García AJ
Published in Science Advances on May 13, 2022 | *Summary available | Press Release

Insights into Therapy Resistance in Small Cell Lung Cancer
Translesion DNA Synthesis Mediates Acquired Resistance to Olaparib Plus Temozolomide in Small Cell Lung Cancer
Stanzione M, Zhong J, Wong E, LaSalle TJ, Wise JF [et al.], Drapkin BJ
Published in Science Advances on May 13, 2022 | *Summary available

Treatment Strategy for Congenital Giant Nevi Shows Promise
Topical Therapy for Regression and Melanoma Prevention of Congenital Giant Nevi
Choi YS, Erlich TH, von Franque M, Rachmin I, Flesher JL [et al.], Fisher DE
Published in Cell on May 12, 2022 | *Summary available | Press Release

Clinical Outcomes Among Competitive Athletes Who Return to Sports After COVID-19
Cardiovascular Outcomes in Collegiate Athletes Following SARS-CoV-2 Infection: 1-year Follow-up from the Outcomes Registry for Cardiac Conditions in Athletes
Petek BJ, Moulson N, Drezner JA, Harmon KG, Kliethermes SA [et al.], Baggish AL; ORCCA Investigators
Published in Circulation on May 12, 2022 | *Summary available

New Combination Therapy to Treat T-cell Acute Lymphoblastic Leukemia
Combination Therapies to Inhibit LCK Tyrosine Kinase and mTOR Signaling in T-cell Acute Lymphoblastic Leukemia
Laukkanen S, Bacquelaine Veloso A, Yan C, Oksa L [et al.], Langenau DM
Published in Blood on May 11, 2022 | *Summary available

Rare Genetic Variants are Strongly Associated With Hypertrophic Cardiomyopathy
Association of Pathogenic DNA Variants Predisposing to Cardiomyopathy With Cardiovascular Disease Outcomes and All-Cause Mortality
Patel AP, Dron JS, Wang M, Pirruccello JP, Ng K [et al.], Khera AV
Published in JAMA Cardiology on May 11, 2022

Reducing Healthcare Disparities Through Better Polygenic Risk Scores
Improving Polygenic Prediction in Ancestrally Diverse Populations
Ruan Y, Lin YF, Feng YCA, Chen CY, Lam M [et al.], Ge T
Published in Nature Genetics on May 5, 2022 | *Summary available | Press Release

Earlier Screening for Colorectal Cancer Reduces Risk
Age at Initiation of Lower Gastrointestinal Endoscopy and Colorectal Cancer Risk Among U.S. Women
Ma W, Wang M, Wang K, Cao Y, Hertzmark E [et al.], Chan AT
Published in JAMA Oncology on May 5, 2022 | *Summary available | Press Release

Selective Neuron Degeneration in Parkinson's Disease
Single-cell Genomic Profiling of Human Dopamine Neurons Identifies a Population That Selectively Degenerates in Parkinson's Disease
Kamath T, Abdulraouf A, Burris SJ, Langlieb J, Gazestani V [et al.], Macosko EZ
Published in Nature Neuroscience on May 5, 2022

Correlates of Immunity to SARS-CoV-2
Defining the Determinants of Protection Against SARS-CoV-2 Infection and Viral Control in a Dose-down Ad26.CoV2.S Vaccine Study in Nonhuman Primates
Zhu DY, Gorman MJ, Yuan D, Yu J, Mercado NB [et al.], Alter G
Published in PLoS Biology on May 5, 2022

The Ventrolateral Prefrontal Cortex Contains Nodes for the Salience Network
Anatomical and Functional Connectivity Support the Existence of a Salience Network Node Within the Caudal Ventrolateral Prefrontal Cortex
Trambaiolli LR, Peng X, Lehman JF, Linn G, Russ BE [et al.], Haber SN
Published in eLife on May 5, 2022

A Rapid, Robust and Low Cost Solution to High-dimensional Analysis of Cancer Cells
Integrated Analytical System for Clinical Single-Cell Analysis
Peterson HM, Chin LK, Iwamoto Y, Oh J, Carlson JCT [et al.], Weissleder R
Published in Advanced Science on May 4, 2022

Looking at the Role of GIT1-interacting Synaptic Proteins in Schizophrenia
Brain-specific Deletion of GIT1 Impairs Cognition and Alters Phosphorylation of Synaptic Protein Networks Implicated in Schizophrenia Susceptibility
Fass DM, Lewis MC, Ahmad R, Szucs MJ, Zhang Q [et al.], Haggarty SJ
Published in Molecular Psychiatry on May 3, 2022

Dynamin-activating Drugs as Novel Therapies for AKI
Simultaneous Stabilization of Actin Cytoskeleton in Multiple Nephron-specific Cells Protects the Kidney From Diverse Injury
Mukherjee K, Gu C, Collins A, Mettlen M, Samelko B [et al.], Sever S
Published in Nature Communications on May 3, 2022 | *Summary available

Affirmative Action Bans Reduced Number of URM Medical Students
Affirmative Action Bans and Enrollment of Students From Underrepresented Racial and Ethnic Groups in U.S. Public Medical Schools
Ly DP, Essien UR, Olenski AR, Jena AB
Published in Annals of Internal Medicine on May 3, 2022

Skull Channels Allow CSF to Flow Out of the Brain Into Skull Marrow
Cerebrospinal Fluid Can Exit Into the Skull Bone Marrow and Instruct Cranial Hematopoiesis in Mice With Bacterial Meningitis
Pulous FE, Cruz-Hernández JC, Yang C, Kaya Ζ, Paccalet A [et al.], Nahrendorf M
Published in Nature Neuroscience on May 2, 2022 | *Summary available | Press Release

Plasma cfDNA May Have Prognostic Value in Lung Cancer
Circulating Cell-free DNA as a Prognostic Biomarker in Patients With Advanced ALK+ Non-Small Cell Lung Cancer in the Global Phase III ALEX Trial
Dziadziuszko R, Peters S, Mok T, Camidge DR, Gadgeel SM [et al.], Shaw AT
Published in Clinical Cancer Research on May 2, 2022

CT Scans of Chest Wall Muscle Predicts Adverse Outcomes in Lobectomy for Lung Cancer
Multilevel Body Composition Analysis on Chest Computed Tomography Predicts Hospital Length of Stay and Complications After Lobectomy for Lung Cancer: A Multicenter Study
Best TD, Mercaldo SF, Bryan DS, Marquardt JP, Wrobel MM [et al.], Fintelmann FJ
Published in Annals of Surgery on May 1, 2022 | *Summary available

Insights to Guide Drug Development for BRAF-targeted Kinase Inhibitors
Overcoming Differential Tumor Penetration of BRAF Inhibitors Using Computationally Guided Combination Therapy
Ng TSC, Hu H, Kronister S, Lee C, Li R, Gerosa L [et al.], Miller MA
Published in Science Advances on April 29, 2022

Unprecedented High Resolution Imaging of the Pial Arteries
Imaging of the Pial Arterial Vasculature of the Human Brain In Vivo Using High-resolution 7T Time-of-Flight Angiography
Bollmann S, Mattern H, Bernier M, Robinson SD, Park DJ, Speck O, Polimeni JR
Published in Elife on April 29, 2022 | *Summary available

Alarming Rise in Opioid Overdose Deaths Among Non-Hispanic Black People
Racial Disparities in Opioid Overdose Deaths in Massachusetts
Liao CY, Garcia GP, DiGennaro C, Jalali MS
Published in JAMA Network Open on April 28, 2022 | *Summary available

Black Patients Less Likely to Be Treated With Proton Beam Therapy
Association of Race With Receipt of Proton Beam Therapy for Patients With Newly Diagnosed Cancer in the U.S., 2004-2018
Nogueira LM, Sineshaw HM, Jemal A, Pollack CE, Efstathiou JA, Yabroff KR
Published in JAMA Network Open on April 27, 2022

Income-related Disparities in Stroke Disability
Association of Socioeconomic Status and Infarct Volume With Functional Outcome in Patients With Ischemic Stroke
Ghoneem A, Osborne MT, Abohashem S, Naddaf N, Patrich T [et al.], Tawakol A
Published in JAMA Network Open on April 27, 2022 | *Summary available

Genetic Susceptibility and Diet Quality are Independent Risk Factors for Diabetes
Polygenic Scores, Diet Quality, and Type 2 Diabetes Risk: An Observational Study Among 35,759 Adults From 3 U.S. Cohorts
Merino J, Guasch-Ferré M, Li J, Chung W, Hu Y [et al.], Hu FB
Published in PLoS Medicine on April 26, 2022 | *Summary available

Publication Summaries

There is an urgent need to identify strategies to limit the development of alcohol-associated liver disease, one of the most feared complications of excessive alcohol use, especially since alcohol use is rising. We studied whether medical treatment for excessive alcohol use in patients with alcohol use disorder was associated with a lower risk of developing alcohol-associated liver disease. We found that in 9,635 patients with alcohol use disorder, those who received medical therapy for alcohol use had a significantly lower risk of developing liver disease, and in patients with already established liver disease, those on medical therapy were less likely to have worsening of their liver disease. Findings from this study suggest an association between use of medical therapy for alcohol and decreased incidence and progression of ALD.

(Summary submitted by Jay Luther, MD, Division of Gastroenterology, Department of Medicine)

Low oxygen levels in tumors—resulting from abnormal blood vessels—promote invasion and metastasis, and confer resistance to various treatments. We previously developed two approaches to improve the function of tumor vessels and oxygenation. Here, we developed a novel microscopy technique to assess blood vessels and oxygen levels at a high resolution in preclinical models of tumors. We found that treatment using an antiangiogenic agent versus losartan—a drug approved for controlling blood pressure—affects blood vessels and oxygen delivery differently. Our findings suggest ways to improve the use of these approaches alone and in combination to improve cancer treatment.

(Summary submitted by Rakesh K. Jain, PhD, Department of Radiation Oncology, Mass General Cancer Center)

Hypertrophic cardiomyopathy (HCM) is a cardiac disorder with a substantial genetic component. A number of rare genetic variants that confer a significant predisposition to HCM have been identified, although many still lack conclusive evidence. More recently, common genetic variants have also been linked to HCM. This study finds strong associations of rare variants in several genes—ncluding MYBPC3, MYH7, and ALPK3—and HCM. The study then validates a polygenic score, which aggregates risk profiles from many common genetic variants, and suggests that both rare and common genetic factors contribute significantly to HCM risk in the population and improve disease prediction.

(Summary submitted by Krishna G. Aragam, MD, Division of Cardiology, Department of Medicine)

In this U.S .population-based study, the use of antenatal steroids increased significantly after new evidence was published on its benefit in reducing neonatal respiratory complications in infants born in the late preterm period. Correspondingly, a reduction in assisted ventilation use in neonates born at these gestational ages was also observed as steroid use increased, suggesting the effects of this intervention are generalizable outside the context of a clinical trial.

(Summary submitted by Mark A. Clapp, MD, MPH, Department of Obstetrics and Gynecology)

The pro-survival protein BCL2 is expressed at high levels in most ER-positive breast tumors. We conducted a randomized phase 2 study evaluating the BCL2 inhibitor venetoclax in patients with ER-positive metastatic breast cancer that had progressed following endocrine and CDK4/6 inhibitor therapy. The addition of venetoclax to fulvestrant failed to improve clinical benefit rate or progression-free survival. Exploratory analysis, however, revealed a trend favoring venetoclax where tumors exhibited strong (IHC 3+) BCL2 expression, a BCL2/BCLXL Histoscore ratio ≥1, or were PIK3CA-wildtype. These hypothesis-generating data suggest a dependence on BCLXL for tumor survival in the post-CDK4/6 inhibitor setting.

(Summary submitted by Aditya Bardia MD, MPH, Breast Cancer Research Program, Division of Hematology/Oncology, Mass General Cancer Center)

Psychiatric disorders in childhood greatly increase the likelihood of developing nicotine and other substance use disorders (SUD) in adulthood. However, it remains unclear whether treating these disorders with medications changes the risk to develop SUD. To address this, we examined 26 prior studies on the impact of psychopharmacology on the development of SUD—21 focused on ADHD, two on major depressive disorder, three on psychotic disorder. These studies included nearly six million individuals. Most studies showed that treatment either reduced substance use or had no effect. Overall, it appeared that pharmacological treatments during childhood appeared to reduce the development of SUD by about one-third, especially when treatment is initiated early and for longer duration.

(Summary submitted by Amy Berger, Pediatric Psychopharmacology & Adult ADHD Program, Department of Psychiatry)

Medication errors occur in 40% of operations and have high potential for patient harm. We developed a comprehensive clinical decision support (CDS) software platform to prevent medication errors in the operating room. This randomized controlled trial compares the usability of the new CDS software platform to the current standard methods for medication administration and documentation. The CDS software outperformed the standard methods, resulting in 20% less time spent by clinicians on documentation, and improved quality of care. For example, patients of clinicians who used the CDS had better blood pressure control and more accurate medication dosing. Our goal is to bring the software to hospitals across the U.S., making surgery and anesthesia safer for all patients.

(Summary submitted by Karen C. Nanji, MD, MPH, Department of Anesthesia, Critical Care and Pain Medicine)

Updated PSA Screening Guidelines Could Reduce Prostate Cancer Mortality Rates
Association of the USPSTF Grade D Recommendation Against Prostate-Specific Antigen Screening With Prostate Cancer-specific Mortality
Burgess L, Aldrighetti CM, Ghosh A, Niemierko A, Chino F, Huynh MJ, Efstathiou JA, Kamran SC
Published in JAMA Network Open on May 16, 2022

This cross-sectional study found that overall prostate cancer-specific mortality rates were decreasing annually prior to the 2012 USPSTF Grade D recommendation against prostate-specific antigen (PSA) screening, with rates flattening or increasing after the change in screening guideline. This was also associated with increased diagnoses of metastatic prostate cancer. This finding was observed across ages, races and ethnicities, urbanization categories and U.S. Census regions, but was particularly striking among Black men, men aged 60 to 69 years, and those aged 80 years or older. The updated 2018 USPSTF guideline supporting shared decision making with respect to PSA screening may reverse these trends in the coming years.

(Summary submitted by Sophia C Kamran, MD, Department of Radiation Oncology, Mass General Cancer Center)

Fluorescence-guided surgery aids surgeons with real-time visualization of small cancer foci and borders, improving surgical and prognostic efficacy of cancer. We developed a novel near-infrared fluorophore PH08, which is 1) a pH-sensitive in acidic tumor microenvironments, 2) the structure inherent targeting via organic anion transporter peptides, and 3) mitochondrial and lysosomal retention. After topical application of PH08 to ovarian cancer-bearing mice, a rapid increase (< 10 minutes), and an extension (> 4 hours) of fluorescence signal were observed, which allow visualization of submillimeter tumors. PH08 provides strategies not only for surgical and diagnostic applications but also for designing therapeutic agents for a wide array of cancers.

(Summary submitted by Shinya Yokomizo, PhD, Gordon Center for Medical Imaging, Department of Radiology)

We developed a novel biomaterial called SA-FasL microgel that has the properties of promoting transplanted graft natural acceptance. This biomaterial supports graft survival after transplantation, so that the recipient doesn’t then have to take immunosuppressive drugs for the long term to prevent rejection. The material was mixed with insulin-producing pancreatic islet cells and transplanted to a bioengineered pouch formed by a fold of fatty tissue located inside abdominal cavity, in a nonhuman primate model of type 1 diabetes. These strategies that created a local immune-privileged environment allow islets to survive but without need lifelong immunosuppression and achieved robust blood sugar control for more than six months. This primate study is highly relevant pre-clinical research. We are confident that patients with type 1 diabetes could have a powerful new treatment option. Also, our technology provides the flexibility of an off-the-shelf product for wider clinical applications of other types of new cell therapy such as bioengineered cells or stem cell derived cells.

(Summary submitted by Ji Lei, MD, MBA, MSc, Center for Transplantation Sciences, Department of Surgery)

Small cell lung cancer (SCLC) is an aggressive and difficult to treat malignancy that affects more than 30,000 people per year. Following a brief initial response to chemotherapy, almost every patient relapses and their response to further chemotherapy is greatly reduced. Our team compared the DNA damage response in patient-derived xenograft (PDX) models generated from the same patient before and after relapse. We have found that hyperactivation of translesion DNA synthesis (TLS) enabled tolerance of chemotherapy-induced damage. TLS inhibitors restored sensitivity to therapy both in vitro and in vivo and similar synergistic effects were seen in additional SCLC cell lines.

(Summary submitted by Marcello Stanzione, PhD, Mass General Cancer Center)

Giant Congenital Nevi (CGN) occur in about 1 in 20,000 babies. They carry a risk of melanoma transformation, in addition to severe cosmetic challenges. This study generated multiple CGN mouse models, based on the same gene (NRAS) which causes the lesion in humans. Using the models, topical drug treatments were tested for regressing the lesions. One such treatment fully regressed the CGNs in mice, fully protected against melanoma formation, and induced significant regressions in discarded human giant nevi that were engrafted onto immunodeficient mice. The study suggests approaches for improved therapy in children with these lesions.

(Summary submitted by David Fisher, MD, PhD, Mass General Cancer Center, Cutaneous Biology Research Center, Department of Dermatology)

Concerns for cardiac involvement following COVID-19 infection led to widespread cancellation of sports followed by extensive efforts to screen athletes for cardiac complications following infection. Until recently, clinical outcomes among competitive athletes who return to sports after COVID-19 have been lacking. In this study, we found an exceedingly low prevalence of adverse cardiac outcomes in >1 year follow-up among a large cohort of >3,600 athletes from 45 colleges after COVID-19 infection. These findings provide definitive reassurance and will inform future guidelines for providers on return-to-play following COVID-19 infection among young competitive athletes.

(Summary submitted by Bradley J. Petek, MD, Division of Cardiology, Department of Medicine)

We uncovered a new combination therapy that kills ~45% of human T-cell acute lymphoblastic leukemias (T-ALL), including aggressive resistant leukemias that are the major clinical challenge facing patients. This work raises hope of complexing dasatinib kinase inhibitor and temsirolimus mTOR inhibitor for clinical evaluation in the future. We also identified the mechanism of action for these drugs and uncovered the unanticipated importance of T-cell receptor signaling in promoting growth and survival of a large fraction of human T-ALL.

(Summary submitted by David M. Langenau, PhD, Department of Pathology)

Polygenic risk scores (PRS) use genetic information to predict individuals’ disease risk and have shown promise in early diagnosis and prevention of disease. However, the prediction accuracy of current PRS is limited in non-European populations. Leveraging genomic data recently collected from underrepresented populations, we developed a new computational method, PRS-CSx, that integrates genomic data from multiple populations and substantially improves the predictive performance of PRS in ancestrally diverse individuals. The method, coupled with the rapidly expanding genomic resources in non-European populations, may facilitate the implementation of PRS in clinical settings and help reduce healthcare disparities.

(Summary submitted by Tian Ge, PhD, Center for Genomic Medicine, Department of Psychiatry)

While there has been an increase in the incidence of colorectal cancer in recent decades in younger individuals, screening has largely been focused on people over 50 years of age. Although screening guidelines were recently revised to recommend starting screening at 45 years of age, data to support this recommendation are lacking. We therefore conducted a prospective study that included 111,801 U.S. women from the Nurses’ Health Study II and showed that initiating an endoscopy before 50 years of age was associated with more than a 50% reduction in risk of colorectal cancer. Initiating an endoscopy from 45 to 49 years old was also associated with a greater reduction in the population’s overall burden of colorectal cancer compared with initiating after 50 years of age. These results provide first-of-its-kind data demonstrating the impact of earlier screening for colorectal cancer on both individual and population-wide scales.

(Summary submitted by Wenjie Ma, ScD, Clinical and Translational Epidemiology Unit, Mongan Institute Health Policy Center, Department of Medicine)

Acute kidney injury (AKI) is when the kidneys suddenly stop working properly, commonly due to cancer chemotherapy, contrast dye used during MRI, or viral infections such as COVID-19. A hallmark of AKI is an injury to kidney tubule cells. These injured kidney cells lose their shape because they lose actin protein filaments (F-actin) that are critical for cell structure maintenance. We show that another protein, dynamin, binds to multiple F-actin when activated and protects F-actin from breaking down during cell injury. Using animal models of AKI, our study proposes the utility of dynamin activating drugs as novel therapies for AKI.

(Summary submitted by Sanja Sever, PhD, Division of Nephrology, Department of Medicine)

Cerebrospinal fluid can exit into the skull’s marrow through tiny channels. Immune cells produced in the skull marrow can screen the cerebrospinal fluid for signs of infection. In 2018, our team had found that immune cells responding to brain injury come from skull marrow, passing through hundreds of tiny channels. Now the team reported that skull channels allow the cerebrospinal fluid to flow in the opposite direction, out of the brain and into the skull marrow. During meningitis, bacteria travel through the channels and enter the skull’s bone marrow, which in response produces more immune cells to combat the infection.

(Summary submitted by Matthias Nahrendorf, MD, PhD, Center for Systems Biology)

In this multicenter study we confirm that chest wall muscle measured on routine preoperative computed tomography (CT) scans predicts adverse outcomes following lobectomy for lung cancer. The effect of muscle was independent of patient age, pulmonary function, body mass index, surgical approach, smoking status, and performance score. Current risk prediction models prior to lung resection rely mainly on cardiovascular history and pulmonary function testing. The concept that information from routinely acquired preoperative computed tomography examinations improves patient-level risk prediction for adverse outcomes following lung resection has the potential to improve the care of patients with operable lung cancer.

(Summary submitted by Florian J. Fintelmann, MD, Department of Radiology, Mass General Cancer Center)

The arterial blood vessels lining the surface of the brain play an important role in blood delivery in health and disease. Their anatomical layout dictates the resiliencies and vulnerabilities of supply, yet because of their small diameter these vessels have not yet been imaged in humans in vivo. Here the pial arteries of the cerebral cortex were imaged using ultra-high-field MRI at unprecedented resolutions. Imaging resolution was found to be the main limiting factor to mapping these arteries, not their slow blood flow. Using advanced techniques to achieve resolutions below 200 micrometers, a more complete picture of these vessels emerged.

(Summary submitted by Jonathan R. Polimeni, PhD, Martinos Center, Department of Radiology)

New analysis shows that excess opioid-related overdose deaths increased in Massachusetts during COVID-19; critically, the increase was driven primarily by rising excess mortality among non-Hispanic Black people. In other words, opioid-related overdose deaths among non-Hispanic Black people exceeded what was expected, while deaths among other racial groups were less than expected. This is an alarming pattern that would not have been observed with aggregated data. We discuss data reporting challenges in other states and call for timely, disaggregated reporting of overdose data by states and CDC to facilitate the analysis of disparities, essential for the design of equitable interventions.

(Summary submitted by Mohammad S. Jalali, PhD, MSc, MGH Institute for Technology Assessment, Department of Radiology)

Use of Proton Beam Therapy has Increased
Assessment of Proton Beam Therapy Use Among Patients With Newly Diagnosed Cancer in the U.S., 2004-2018
Nogueira LM, Jemal A, Yabroff KR, Efstathiou JA
Published in JAMA Network Open on April 27, 2022

Black Patients Less Likely to Be Treated With Proton Beam Therapy
Association of Race With Receipt of Proton Beam Therapy for Patients With Newly Diagnosed Cancer in the U.S., 2004-2018
Nogueira LM, Sineshaw HM, Jemal A, Pollack CE, Efstathiou JA, Yabroff KR
Published in JAMA Network Open on April 27, 2022

Proton beam therapy (PBT) is a high-tech, expensive and potentially superior form of radiation therapy (compared to photons) especially for tumors with complex anatomy, those surrounded by sensitive tissues, and childhood cancers. In companion cross-sectional studies that analyzed national data on nearly 6 million patients, PBT use for newly diagnosed cancers increased in the United States (0.4% in 2004 to 1.2% in 2018) especially for cancer sites for which PBT use is the recommended treatment modality (group 1), but also for sites for which effectiveness of PBT over other radiotherapy modalities is still being investigated (group 2). Breast and prostate cancers (both group 2) are most frequently treated with PBT. Notably, however, Black patients were less likely to be treated with PBT than white patients (0.3% vs. 0.5%), especially for cancers for which PBT is recommended over traditional radiation therapy. This racial disparity in receipt of PBT increased over time despite increases in the number of facilities offering PBT in the U.S., and the disparity did not disappear after accounting for socioeconomic status or type of health insurance. Efforts other than increasing the number of facilities that provide PBT will be needed to eliminate these disparities.

(Summary submitted by Jason A. Efstathiou, MD, DPhil, Department of Radiation Oncology, Mass General Cancer Center)

Patients with lower income have greater long-term disability from strokes. While differences in post-stroke care were previously thought to account for this difference, we studied whether biological factors present before the hospitalization may be complicit. We imaged over 1,200 patients as they first presented with strokes. We found that as income decreased, the volume of the brain impacted by the stroke increased, and that this was accounted for by arterial and clotting factors. Income-related differences in stroke size were not caused by risk factors or prior treatments. Further, initial stroke size accounted for the differences in long term disability. These findings shift the culpability for income-related disparities in stroke disability: from differences in stroke care to biological factors that precede presentation.

(Summary submitted by Ahmed Tawakol, MD, Division of Cardiology, Department of Medicine)

A new study analyzed data from three cohort studies, including 35,759 U.S. health professionals followed for more than 20 years. The team found that genetic susceptibility and diet quality are independently associated with the risk of developing diabetes. The combination of having a high genetic risk for diabetes and low diet quality was associated with increased disease risk, but the contribution of the two factors together was similar to the effect of each factor separately. The study also provided evidence that low diet quality, compared to high diet quality, was associated with a 30% increased risk of type 2 diabetes regardless of genetic risk. These findings support public health efforts that emphasize the consumption of healthy dietary patterns to prevent diabetes.

(Summary submitted by Jordi Merino, PhD, Center for Genomic Medicine)

Press Releases

New Insights on the Importance of Skull Channels for Brain Health
Featuring Matthias Nahrendorf, MD, PhD

Channels allow “brain water” to exit the brain and be screened by immune cells in the skull’s bone marrow.

Brain Connectivity Changes Revealed in Individuals With Pre-Clinical Alzheimer’s Disease
Featuring Yakeel Quiroz-Gaviria, PhD

Accumulation of amyloid-β and tau proteins are related to brain network changes years before symptoms.

A Unique Machine-learning Model Predicts Homelessness Among U.S. Soldiers Before Their Transition to Civilian Life
Featuring Katherine A. Koh, MD, MSc

A study by a Mass General-led team could lead to more targeted strategies to prevent homelessness among military personnel.

New Tool More Accurately Uses Genomic Data to Predict Disease Risk Across Diverse Populations
Featuring Yunfeng Ruan, PhD, and Tian Ge, PhD

Integrating data from different ancestries reduces bias in predicting disease risk.

Starting Screening Before Age 50 Is Found to Significantly Reduce the Risk and Incidence of Colorectal Cancer in Women
Featuring Wenjie Ma, ScD, and Andrew T. Chan, MD, MPH

Research from a Mass General study could have major healthcare implications on both individual and population-wide scales.

Skin Drug Treatments May Regress Dangerous Birthmarks and Prevent Melanoma
Featuring David Fisher, MD, PhD

Congenital giant nevi, which are often treated with disfiguring surgeries, carry an increased risk of skin cancer.

Novel Biomaterial Prevents Rejection of Transplants for Type 1 Diabetes
Featuring Ji Lei, MD, MBA, MSc, and James F. Markmann, MD, PhD

Clinical trial is planned based on results from preclinical study.

New Clinical Support Software Improves Efficiency and Quality of Care in the Operating Room
Featuring Karen C. Nanji, MD, MPH

Preventing medication administration errors and improving efficiency during surgery enhances patient care.

Scientists Develop and Monitor Two Approaches to Fix Blood Vessel Abnormalities That Make Tumors Difficult to Treat
Featuring Rakesh K. Jain, PhD

Combining the approaches may be a powerful anti-cancer strategy.

Medication Treatment of Pediatric Psychiatric Disorders Reduces the Later Onset of Substance Use Problems
Featuring Timothy Wilens, MD

Early and longer-lasting treatment reduces risk of substance use disorder most significantly.

Blog Posts

Conversations on Mental Health: Sharmin Ghaznavi, MD, PhD & The Center for the Neuroscience of Psychedelics
Featuring Sharmin Ghaznavi, MD, PhD

Mass General researchers are testing the psychedelic compound psilocybin as a therapeutic for treatment-resistant depression.

How A New Tool Can Help the Media Responsibly Report on Suicide
Featuring Chloe Chang Sorensen

TEMPOS is a user-friendly rating scale that can be used to assess adherence to reporting recommendations.

Humans of MGRI: Sarasa Tohyama, PhD
Featuring Sarasa Tohyama, PhD

Our next guest in the series is Sarasa Tohyama, PhD, a postdoctoral research fellow in the lab of Vitaly Napadow, PhD, at the Spaulding Rehabilitation Hospital and Mass General Martinos Center for Biomedical Imaging.

Remembering Elizabeth Robinson Scovil, a Pioneering Nurse, Health Communicator and Women’s Advocate
Scovil was one of the first nurses to be formally trained at Mass General and was a prolific author and advice columnist for women.

Mass General Expert Explains How You Can Reduce Your Risk of a Stroke
Featuring Natalia Rost, MD, MPH

The good news is that most strokes are preventable, treatable and beatable, says Natalia Rost, MD, MPH, chief of the Stroke Division.

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Snapshot of Science for May 2022