Snapshot of Science for February 2022

Welcome to our Snapshot of Science for February 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:

32 new studies published in high-impact journals, along with 28 summaries submitted by the research teams
18 new research-related press releases from the Mass General Public Affairs office
7 posts from the Mass General Research Institute blog

Publications

Lipoprotein(a) Levels Do Not Fluctuate Over Time
Repeat Measures of Lipoprotein(a) Molar Concentration and Cardiovascular Risk
Trinder M, Paruchuri K, Haidermota S, Bernardo R, Zekavat SM [et al.], Natarajan P
Published in Journal of the American College of Cardiology on Tuesday, February 22, 2022 | *Summary available

A Woman's Reproductive History Can Predict Future Heart Disease
Pregnancy and Reproductive Risk Factors for Cardiovascular Disease in Women
O'Kelly AC, Michos ED, Shufelt CL, Vermunt JV, Minissian MB [et al.], Honigberg MC
Published in Circulation Research on Friday, February 18, 2022 | *Summary available

Combination Treatment for Prostate Cancer Shows Promise
Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer
Smith MR, Hussain M, Saad F, Fizazi K [et al.], Tombal B; ARASENS Trial Investigators
Published in New England Journal of Medicine on Thursday, February 17, 2022

Understanding the Role of Rare Gene Variants in Cardiometabolic Disease
Analysis of Rare Genetic Variation Underlying Cardiometabolic Diseases and Traits among 200,000 Individuals in the UK Biobank
Jurgens SJ, Choi SH, Morrill VN, Chaffin M, Pirruccello JP [et al.], Ellinor PT
Published in Nature Genetics on Thursday, February 17, 2022 | *Summary available

Sex Differences in Biomarkers for Cardiovascular Disease
Sexual Dimorphism in Cardiovascular Biomarkers: Clinical and Research Implications
Lau ES, Binek A, Parker SJ, Shah SH, Zanni MV [et al.], Ho JE
Published in Circulation Research on Thursday, February 17, 2022 | *Summary available

New Insights into RNA and the Origin of Life
Nonenzymatic Assembly of Active Chimeric Ribozymes from Aminoacylated RNA Oligonucleotides
Radakovic A, DasGupta S, Wright TH, Aitken HRM, Szostak JW
Published in PNAS on Tuesday, February 15, 2022 | *Summary available

Tisagenlecleucel Is Safe & Effective for Patients With Primary CNS Lymphoma
Safety and Efficacy of Tisagenlecleucel in Primary CNS Lymphoma: A phase I/II clinical trial
Frigault MJ, Dietrich J, Gallagher KME, Roschewski MJ, Jordan JT [et al.], Chen YB
Published in Blood on Tuesday, February 15, 2022 | *Summary available

Patients With Multiple Myeloma Suffer Poor Quality of Life
Quality of Life, Psychological Distress, and Prognostic Perceptions in Patients with Multiple Myeloma
O'Donnell EK, Shapiro YN, Yee AJ, Nadeem O, Hu BY [et al.], El-Jawahri A
Published in Cancer on Tuesday, February 15, 2022 | *Summary available

Preeclampsia Can Lead to Cardiovascular Issues Later in Life
Microvascular Outcomes in Women With a History of Hypertension in Pregnancy
Honigberg MC, Zekavat SM, Raghu VK, Natarajan P
Published in Circulation on Tuesday, February 15, 2022 | *Summary available

Masks and Vaccinations Lower COVID-19 Infections in Schools
Model-Estimated Association Between Simulated US Elementary School-Related SARS-CoV-2 Transmission, Mitigation Interventions, and Vaccine Coverage Across Local Incidence Levels
Giardina J, Bilinski A, Fitzpatrick MC, Kendall EA, Linas BP [et al.], Ciaranello AL
Published in JAMA Network Open on Monday, February 14, 2022 | *Summary available

Lighting-Up Ovarian Cancer for Surgery
Fast and Durable Intraoperative Near-infrared Imaging of Ovarian Cancer Using Ultrabright Squaraine Fluorophores
Fukuda T, Yokomizo S, Casa S, Monaco H, Manganiello S [et al.], Choi HS
Published in Angewandte Chemie International Edition English on Saturday, February 12, 2022 | *Summary available

Restoring Gene Function to Supress Liver Cancer, Enhance Immunotherapy
Combining p53 mRNA nanotherapy with immune checkpoint blockade reprograms the immune microenvironment for effective cancer therapy
Xiao Y, Chen J, Zhou H, Zeng X [et al.], Duda DG, Shi J.
Published in Nature Communications on Tuesday, February 9, 2022 | *Summary available

Diabetes Drug Can Lower Risk of Cardiac Issues
Stress Cardiac Biomarkers, Cardiovascular and Renal Outcomes, and Response to Canagliflozin
Vaduganathan M, Sattar N, Xu J, Butler J, Mahaffey KW [et al.], Januzzi JL Jr
Published in Journal of the American College of Cardiology on Tuesday, February 8, 2022 | *Summary available

Newborns Benefit from Maternal Flu Vaccination During Pregnancy
Dissecting Fc Signatures of Protection in Neonates Following Maternal Influenza Vaccination in a Placebo-controlled Trial
Boudreau CM, Burke JS 4th, Shuey KD, Wolf C, Katz J [et al.], Alter G
Published in Cell Reports on Tuesday, February 8, 2022 | *Summary available

Maternal Antibodies from COVID-19 Vaccination Persist in the Infant
Durability of Anti-Spike Antibodies in Infants After Maternal COVID-19 Vaccination or Natural Infection
Shook LL, Atyeo CG, Yonker LM, Fasano A, Gray KJ, Alter G, Edlow AG
Published in JAMA on Monday, February 7, 2022 | *Summary available

Medication Can Help Hearts Grow to Protect Against Heart Failure
lncExACT1 and DCHS2 Regulate Physiological and Pathological Cardiac Growth
Li H, Trager LE, Liu X, Hastings MH, Xiao C [et al.], Rosenzweig A
Published in Circulation on Friday, February 4, 2022 | *Summary available

New Treatment for Advanced Prostate Cancer
Niraparib in Patients with Metastatic Castration-resistant Prostate Cancer and DNA Repair Gene Defects (GALAHAD): A Multicentre, Open-label, Phase 2 Trial
Smith MR, Scher HI, Sandhu S, Efstathiou E [et al.], Fizazi K; GALAHAD investigators
Published in The Lancet Oncolonogy on Friday, February 4, 2022 | Press Release

Postponing Elective Surgery During the Pandemic Reduced Mortality Rates
Outcomes and Their State-level Variation in Patients Undergoing Surgery With Perioperative SARS-CoV-2 Infection in the USA: A Prospective Multicenter Study
COVIDSurg Collaborative
Published in Annals of Surgery on Tuesday, February 1, 2022 | *Summary available

Postponing Elective Surgery in Patients With COVID-19 Infections Reduced Post Surgery Complications
The Risk of Postoperative Complications After Major Elective Surgery in Active or Resolved COVID-19 in the United States
Deng JZ, Chan JS, Potter AL, Chen YW, Sandhu HS [et al.], Yang CJ
Published in Annals of Surgery on Tuesday, February 1, 2022 | *Summary available

Vaccine Hesitancy Among Racial Minorities Suggest Disparities in Vaccine Access
Self-reported COVID-19 Vaccine Hesitancy and Uptake Among Participants from Different Racial and Ethnic Groups in the United States and United Kingdom
Nguyen LH, Joshi AD, Drew DA, Merino J [et al.], Chan AT; COPE Consortium
Published in Nature Communications on Tuesday, February 1, 2022 | *Summary available

Mechanism Links Male Adolescent TBI to Later Neurodegeneration
Repetitive Mild Closed Head Injury in Adolescent Mice Is Associated With Impaired Proteostasis, Neuroinflammation, and Tauopathy
Wu L, Kalish BT, Finander B, Cao T, Jin G [et al.], Whalen MJ
Published in The Journal of Neuroscience on Tuesday, February 1, 2022 | *Summary available

New Imaging Technique to Visualize Microtubule Activity
Atomic Force Microscopy Reveals Distinct Protofilament-scale Structural Dynamics in Depolymerizing Microtubule Arrays
Wijeratne SS, Marchan MF, Tresback JS, Subramanian R
Published in PNAS on Tuesday, February 1, 2022 | *Summary available

Injectable HIV Prevention Treatment May Cost More than Generic Pill Treatment
Cost-Effectiveness of Long-Acting Injectable HIV Preexposure Prophylaxis in the United States : A Cost-Effectiveness Analysis
Neilan AM, Landovitz RJ, Le MH, Grinsztejn B, Freedberg KA [et al.], Walensky RP
Published in Annals of Internal Medicine on Tuesday, February 1, 2022 | *Summary available

Counties With More Primary Care Physicians Had Higher COVID-19 Vaccination Rates
Association of Primary Care Physicians Per Capita With COVID-19 Vaccination Rates Among US Counties
Lo CH, Chiu L, Qian A, Khan MZ, Alhassan HA [et al.] , Chan AT
Published in JAMA Network Open on Tuesday, February 1, 2022 | *Summary available

Improved Access to Acute Stroke Care
Estimated Population Access to Acute Stroke and Telestroke Centers in the US, 2019
Zachrison KS, Cash RE, Adeoye O, Boggs KM, Schwamm LH [et al], Camargo CA Jr
Published in JAMA Network Open on Tuesday, February 1, 2022 | *Summary available

Study of Beirut Port Explosion Helps Emergency Preparedness
The Beirut Port Explosion Injuries and Lessons Learned: Results of the Beirut Blast Assessment for Surgical Services (BASS) Multicenter Study
Gebran A, Abou Khalil E, El Moheb M, Albaini O, El Warea M [et al.], Kaafarani HMA
Published in Annals of Surgery on Tuesday, February 1, 2022 | *Summary available

Improving Outcome Predictions in Pancreatic Cancer Patients
A Combination of Biochemical and Pathological Parameters Improves Prediction of Postresection Survival After Preoperative Chemotherapy in Pancreatic Cancer: The PANAMA-score
Hank T, Sandini M, Ferrone CR, Ryan DP, Mino-Kenudson M [et al.], Castillo CF
Published in Annals of Surgery on Tuesday, February 1, 2022

Healthy Eating Can Lower Risk of Gout in Women
Adherence to 2020 to 2025 Dietary Guidelines for Americans and the Risk of New-Onset Female Gout
Yokose C, McCormick N, Lu N, Joshi AD, Curhan G, Choi HK
Published in JAMA Internal Medicine on Monday, January 31, 2022 | *Summary available

Inflammation, Fibrosis and Healing in the Colon
Colon Stroma Mediates an Inflammation-driven Fibroblastic Response Controlling Matrix Remodeling and Healing
Jasso GJ, Jaiswal A, Varma M, Laszewski T, Grauel A [et al.], Graham DB
Published in PLoS Biology on Thursday, January 27, 2022 | *Summary available

Identifying Patients at High Risk of Attempting Suicide
Prediction of Suicide Attempts Using Clinician Assessment, Patient Self-report, and Electronic Health Records
Nock MK, Millner AJ, Ross EL, Kennedy CJ, Al-Suwaidi M [et al.], Kessler RC
Published in JAMA Network Open on Thursday, January 27, 2022

Community-Level Social Support Lowers Rates of Depression
Community-Level Social Support Infrastructure and Adult Onset of Major Depressive Disorder in a South Asian Postconflict Setting
Axinn WG, Choi KW, Ghimire DJ, Cole F, Hermosilla S [et al.], Smoller JW
Published in JAMA Psychiatry on Wednesday, January 26, 2022 | *Summary available

Medication Does Not Increase Death Rate for Patients With Chronic Kidney Disease and Gout
Allopurinol Initiation and All-Cause Mortality Among Patients With Gout and Concurrent Chronic Kidney Disease: A Population-Based Cohort Study
Wei J, Choi HK, Neogi T, Dalbeth N, Terkeltaub R [et al.], Zhang Y
Published in Annals of Internal Medicine on Tuesday, January 25, 2022 | *Summary available

Race and Variability in Advanced Dementia Care
Association of Nursing Home Organizational Culture and Staff Perspectives With Variability in Advanced Dementia Care: The ADVANCE Study
Palan Lopez R, Hendricksen M, McCarthy EP, Mazor KM, Roach A [et al.], Mitchell SL
Published in JAMA Internal Medicine on Monday, January 24, 2022 | *Summary available

New Tool Study Human Cognitive Processes
Large-scale Neural Recordings with Single Neuron Resolution Using Neuropixels Probes in Human Cortex
Paulk AC, Kfir Y, Khanna AR, Mustroph ML, Trautmann EM [et al.], Cash SS.
Published in Published in Nature Neuroscience on February 1, 2022 | *Summary available

Publication Summaries

Lipoprotein(a) is a molecule that exists in the blood that is structurally similar to low-density lipoprotein (LDL or "bad cholesterol"). High levels of LDL or lipoprotein(a) are associated with increased risk of cardiovascular diseases such heart attacks and strokes. However, unlike LDL, lipoprotein(a) may be relatively stable throughout a patient’s life and not require repeat measurement. This study assessed the stability of repeat lipoprotein(a) measurements and the association between lipoprotein(a) instability with incident cardiovascular disease among 16,017 unrelated UK Biobank participants. Intraindividual lipoprotein(a) measurements were highly correlated regardless of time between testing and lipoprotein(a) instability was not significantly associated with cardiovascular disease. These findings suggest that a single measurement of lipoprotein(a), rather than repeat testing, is an efficient method to inform cardiovascular risk.

(Summary submitted by Mark Trinder, MD/PhD candidate, University of British Columbia)

Heart disease is the leading cause of death in women worldwide. Women face well-recognized risk factors for heart disease (e.g., high blood pressure, diabetes) as well as unique sex-specific risk factors. Key stages of a woman’s reproductive history can influence her risk of future heart disease. Our review highlights how menstrual history, pregnancy history, and menopause history (among other reproductive factors) can all influence a woman’s future risk of heart disease. For example, whether a woman developed high blood pressure during pregnancy, or whether she breastfed, both influence her risk of future heart disease. Unfortunately, many women—and many doctors—don’t fully recognize this. It is essential that a woman’s reproductive history be reviewed to best understand her unique risk of heart disease.

(Summary submitted by Anna C. O’Kelly, MD, MPhil, Department of Medicine)

Cardiometabolic diseases, such as heart failure and diabetes, are leading causes of death worldwide. While these common diseases have a genetic basis, the role of rare gene mutations in the overall population has been unclear. Using data on over 200,000 people from the UK Biobank, we studied the role of rare mutations in 83 diseases and traits. We found a striking risk associated with mutations in both known and newly identified cardiometabolic genes. We also found that between 1% to 2.4% of the population carried disease-causing mutations. Our findings have identified cardiometabolic disease genes that can help us to both better understand these diseases and to serve as new potential therapeutic targets.

(Summary submitted by Patrick Ellinor, MD, PhD, Cardiology Division, Department of Medicine)

Heart disease differs between men and women, but we still do not understand why these differences exist. Biomarkers are laboratory-measured markers of normal biologic processes that can be used for disease screening, diagnosis, and risk prediction. This review summarizes differences in biomarkers between men and women, focusing on biomarkers of heart injury, inflammation, obesity and fibrosis. We review how sex chromosomes, hormones, body size and composition, inflammation and sociocultural contributions all contribute to differences in biomarkers between men and women. Finally, we offer recommendations for future proposed research areas and clinical applications of biomarkers to improve the care of men and women with heart disease.

(Summary submitted by Emily Lau, MD, Cardiology Division, Department of Medicine)

The emergence of a primordial ribosome from the RNA world would have required access to aminoacylated RNA substrates. Generating such substrates without enzymes is inefficient, and it remains unclear how they could be selected for in a prebiotic milieu. In our study, we identify a possible role for aminoacylated RNA in ribozyme assembly. We show that aminoacylation of short RNAs greatly accelerates their assembly into functional ribozymes by forming amino acid bridges in the phosphodiester backbone. Our work therefore addresses two key challenges within the origin-of-life field: The rationale for the initial RNA aminoacylation and the assembly of functional ribozymes.

(Summary submitted by Aleksandar Radakovic)

Tisagenlecleucel Is Safe & Effective for Patients With Primary CNS Lymphoma
Safety and Efficacy of Tisagenlecleucel in Primary CNS Lymphoma: A Phase I/II Clinical Trial
Frigault MJ, Dietrich J, Gallagher KME, Roschewski MJ, Jordan JT [et al.], Chen YB
Published in Blood on Tuesday, February 15, 2022

Primary central nervous system lymphoma (PCNSL) is a rare but aggressive disease that can affect any part of the brain or central nervous system. Despite optimal management with high-dose chemotherapy, most patients have disease progression which is associated with poor survival. Immunotherapies with CAR T-cells have shown impressive results in patients with lymphoma but have not been studied in PCNSL. We here report the first prospective clinical trial of using CAR T-cells in PCNSL. Treatment was safe and well tolerated and the majority of patients showed a response to therapy, with a subset of patients with complete remission, paving the path for a novel and promising therapy option in this challenging disease.

(Summary submitted by Jorg Dietrich, MD, PhD, Mass General Cancer Center, Department of Neurology)

We enrolled 180 patients with multiple myeloma (60 newly diagnosed, 60 who had received 2-3 lines, and 60 with ≥4 lines of therapy). Quality of life, symptom burden, and fatigue scores did not differ by lines of therapy. There were also no statistically significant differences in psychological distress by line of therapy. The rates of clinically significant depression, anxiety, and post-traumatic stress disorder symptoms were 23.9%, 23.9%, and 24.4%, respectively. Most patients (84.7%) reported that their oncologist told them their cancer was incurable but only 30.6% acknowledged that they are terminally ill, and 42.0% reported that they thought their cancer was incurable.

(Summary submitted by Elizabeth O'Donnell, MD, Mass General Cancer Center, Department of Medicine)

Previous Preeclampsia Can Lead to Cardiovascular Issues Later in Life
Microvascular Outcomes in Women With a History of Hypertension in Pregnancy
Honigberg MC, Zekavat SM, Raghu VK, Natarajan P
Published in Circulation on Tuesday, February 15, 2022

Gestational hypertension and preeclampsia are pregnancy complications characterized by high blood pressure. Both have been linked to increased risk of heart disease. To understand why, our team used machine learning to define features of the microvasculature in the eyes in ~20,000 women from the UK Biobank who were >20 years post-pregnancy. We also analyzed protein levels in the urine, which is a marker of kidney microvascular health. We found that women with previous preeclampsia had impaired microvascular health in both the eyes and kidneys. This suggests that microvascular disease may be an important mechanism of accelerated cardiovascular aging in women with previous preeclampsia and suggests new avenues for research to prevent CVD.

(Summary submitted by Michael C. Honigberg, MD, MPP, Cardiology Division, Department of Medicine)

In this study, we used a computer model of how SARS-CoV-2 is transmitted among students and educators/staff at school and in their households. Using readily available data—vaccination rates and community COVID-19 case counts—we identified the risk of in-school transmission, number of additional SARS-CoV-2 infections, and SARS-CoV-2 hospitalizations that might be expected if masks were removed. We also provided these estimates over a wide range of possible values for the effectiveness of masks and vaccines in preventing infection. This study highlights that to determine what level of mitigation—including masks—is needed, decision-makers must first clearly articulate their goals. This study then provides quantitative information about likely outcomes to guide decisions that must be made in the absence of empiric data.

(Summary submitted by Andrea L. Ciaranello, MD, MPH, Division of Infectious Diseases, Department of Medicine)

Lighting-Up Ovarian Cancer For Surgery
Fast and Durable Intraoperative Near-infrared Imaging of Ovarian Cancer Using Ultrabright Squaraine Fluorophores
Fukuda T, Yokomizo S, Casa S, Monaco H, Manganiello S [et al.], Choi HS
Published in Angewandte Chemie International Edition English on Saturday, February 12, 2022

Successful ovarian cancer surgery has been well known to contribute to a good patient prognosis. However, complete surgical removal of ovarian cancer, which typically forms disseminated small tumors, remains challenging because surgeons still rely on visual inspection and palpation. To improve ovarian cancer surgery, we developed a novel fluorescence molecule (asymmetric squaraine), which accumulates in ovarian cancer rapidly and is retained in lysosomes in cancer cells. Fluorescence imaging using this molecule realized a high contrast, real-time visualization of a mouse model of ovarian cancer for a long time (up to 24 hours). This imaging method would provide surgeons with an indispensable tool for optimal ovarian cancer surgery.

(Summary submitted by Satoshi Kashiwagi, MD, PhD, Gordon Center for Medical Imaging, Department of Radiology)

During malignant transformation, cancers acquire mutations and gain the ability to evade the immune system. Some of these mutations lead to loss of function of tumor suppressor genes. The tumor suppressor gene p53 is mutated in many cancers, yet effectively restoring its function for treatment remains an unmet need. This preclinical study shows that using mRNA to restore p53 expression—in combination with immune checkpoint blockade to reactivate anti-tumor immunity—can globally reprogram the cellular and molecular components in established liver cancers. This new combinatorial approach could be an effective strategy for treating cancers with loss of p53 function.

(Summary submitted by Dan G. Duda, DMD, PhD, FAIMBE, FAAAS, GI Radiation Oncology, Edwin L. Steele Laboratories for Tumor Biology)

Canagliflozin is a drug called an SGLT2 inhibitor, which is a relatively new class of drug for treating diabetes that has significant benefits to lower risk for cardiovascular events. We evaluated several cardiac biomarkers circulating in the blood of people treated with canagliflozin and found that not only did the drug favorably lower concentrations of these prognostic biomarkers, but also we were able to show that levels of these blood tests BEFORE treatment predicted the benefit of the drug. This suggests biomarker testing might be used to personalize care with SGLT2 inhibitors, allowing us to target the highest risk individuals with the most to benefit.

(Summary submitted by James Januzzi, Jr, MD, Department of Medicine, Division of Cardiology)

Newborns are uniquely vulnerable to influenza infection and illness. One strategy to protect newborns is maternal vaccination during pregnancy. We studied the influenza-specific antibody responses in mothers and infants across vaccine and placebo recipients during a clinical trial in Nepal. Vaccination boosted influenza-specific antibody levels and the ability of antibodies to recruit the antiviral power of the immune system. While overall antibody levels did not differ across mother:infant pairs that were protected or were infected with influenza, antibodies able to direct the antiviral activity of the immune system, via enhanced binding to antibody-Fc-receptors, were enriched in mother:infant pairs that resisted Influenza. These data provide insights on the mechanisms of protection against influenza and provide clues for the design of future vaccines able to protect women and their children.

(Summary submitted by Carolyn Boudreau, PhD, formerly of the Ragon Institute of MGH, MIT, and Harvard)

COVID-19 vaccination in pregnancy generates protective antibodies that pass from mother to baby. Understanding how long maternal antibodies last in infants is important because COVID-19 vaccines are not currently planned for administration to infants younger than 6 months of age, and COVID-19 infections in this age group can be severe. In this study, we found that the majority (57%) of infants born to vaccinated mothers had detectable antibodies at 6 months of age, compared with only 8% of infants born to mothers infected with COVID-19 during pregnancy. This is encouraging news for pregnant individuals who are vaccinated or considering vaccination.

(Summary submitted by Lydia Shook, MD, Department of Obstetrics and Gynecology)

Helping Hearts Grow to Protect Against Heart Failure
lncExACT1 and DCHS2 Regulate Physiological and Pathological Cardiac Growth
Li H, Trager LE, Liu X, Hastings MH, Xiao C [et al.], Rosenzweig A
Published in Circulation on Friday, February 4, 2022

Heart failure, a growing public health challenge that afflicts >60M people around the world, often develops after abnormal heart growth. However, the heart also grows in response to exercise, which paradoxically protects against heart failure. We have discovered one explanation for these very different outcomes in an RNA molecule, lncExACT1, which increases in disease but decreases in exercised hearts. Blocking lncExACT1 with inhibitors similar to FDA-approved drugs reproduces many features of exercised hearts including improving cardiac function in multiple disease models. Investigators are optimistic these results can be translated into new exercise-inspired therapeutic approaches.

(Summary submitted by Haobo Li, PhD, and Anthony Rosenzweig, MD, Department of Medicine)

We conducted a nationwide research project as part of the COVIDSurg Collaborative to collect data from over 1,500 patients admitted to 70 hospitals across 27 states to evaluate the outcomes of patients with COVID-19 who underwent surgery. The study showed that more than one out of 10 patients died after surgery and about 4 out of 10 developed respiratory complications. Certain patient groups were at higher risk for death; these include elderly patients ≥70-year-old, male sex, those undergoing emergent surgery, those with medical conditions such as cancer, respiratory and heart comorbidities. Interestingly, elective surgery cancelation orders were associated with an 85% reduction in mortality in those who underwent elective surgery. We concluded that postponing elective surgery and adopting non-operative management, when reasonable, should be considered in the U.S during the pandemic peaks.

(Summary submitted by Haytham M. Kaafarani, MD, MPH, Department of Surgery)

In this national analysis, we found that patients who had COVID-19 and require non-emergent, elective surgery may have a lower risk of postoperative complication if they can wait to get their operation eight weeks after their recovery from COVID-19. It is important to note though, that for certain cancer patients, delaying surgery can lead to worse long-term survival because of cancer growth or spread occurring during the delay. The balance between the risk of postoperative complications and the risk of worse overall survival associated with delayed surgery needs to be carefully discussed in a multi-disciplinary setting with the patient and the patient’s surgeon and doctors before deciding on whether surgery should be delayed.

(Summary submitted by Chi-Fu Jeffrey Yang, MD, Thoracic Surgery)

Using the COVID Symptom Study smartphone app developed to rapidly conduct population-scale COVID-19 investigations, we performed a multi-national investigation of over 1.2 million individuals to confirm the presence of widespread vaccine hesitancy among racial and ethnic minority individuals. We were also among the first to demonstrate that differences in vaccine uptake in minority populations were not fully explained by higher rates of vaccine hesitancy. This finding strongly suggests important disparities in vaccine access.

(Summary submitted by Long H. Nguyen, MD, Department of Medicine)

Mechanism Links Male Adolescent TBI to Later Neurodegeneration
Repetitive Mild Closed Head Injury in Adolescent Mice Is Associated with Impaired Proteostasis, Neuroinflammation, and Tauopathy
Wu L, Kalish BT, Finander B, Cao T, Jin G [et al.], Whalen MJ
Published in The Journal of Neuroscience on Tuesday, February 1, 2022

Epidemiological studies link repetitive mild traumatic brain injury (TBI) with later life dementia and neurodegenerative disease. However, the cellular and molecular mechanisms linking mild TBI to neurodegeneration are unknown. Using an adolescent mouse model of repetitive closed head injury and single nuclear RNA sequencing, we show that males, but not females, develop progressive cognitive deficits associated with transcriptional and protein changes indicative of impaired neuronal proteostasis. The data are the first to provide a direct link between repetitive mild TBI in adolescence and development of later life neurodegeneration, with new potential therapeutic targets involving inflammatory signaling pathways.

(Summary submitted by Michael J. Whalen, MD, Department of Pediatrics)

Just like how highways organize our macroscopic world, the cytoskeleton organizes the cellular cytoplasm. Microtubules, cylindrical protein polymers, are used to construct micron-sized cytoskeletal arrays with different architectures for diverse cellular functions. Typically, imaging methods which investigate dynamic microtubule-organization are restricted to single microtubules. This is akin to trying to work out how multi-lane highways are built using a DIY manual for single-lane street construction. Here, we demonstrate that a technique called Atomic Force Microscopy permits visualization of individual microtubules within complex arrays and our work reveals how microtubule arrays are precisely sculpted by cellular machinery for different functions.

(Summary submitted by Sitara Wijeratne, PhD, Department of Genetics)

Long-acting injectable HIV pre-exposure prophylaxis (PrEP)—an injection given every two months to prevent HIV—was recently found to be effective at preventing HIV. However, a highly effective, generic oral medication costs $1/day. How much then, should we be willing to pay for injectable PrEP? Using a simulation model, we assessed the maximum price premium of injectable PrEP over generic oral PrEP. We found that injectable PrEP would have the most value in people unable to take a daily pill. The newly announced price of injectable PrEP is more than three times the amount our study estimated, raising concerns that unless priced to reflect its value above generic pills, the people who need injectable PrEP most may be left behind.

(Summary submitted by Anne M. Neilan, MD, MPH, Infectious Disease Unit, Department of Pediatrics)

Maximal population uptake of COVID-19 vaccines has been hindered by vaccine hesitancy. Reports and studies suggest that individuals who are vaccine hesitant are more willing to take advice from their primary care physicians (PCPs). This cross-sectional study of 2,739 counties and county equivalents in the U.S., using data from the U.S. Centers for Disease Control and Prevention and state health departments as of August 23, 2021, found that the number of PCPs per 100,000 population was independently associated with higher COVID-19 vaccination rates among U.S. counties, even in rural areas and more conservative states. These findings support incorporating PCPs into vaccination campaigns.

(Summary submitted by Chun-Han Lo, MD, MPH, Department of Medicine)

Acute stroke care is time-critical. However previous estimates suggested that ~20% of the U.S. population lacked access to disability-reducing, life-saving stroke care. In an updated analysis using data from the National Emergency Department (ED) Inventory–USA and the U.S .Census, an estimated 96% of the population is now within 60-minutes of an ED with acute stroke capabilities (defined as EDs in acute stroke ready hospitals or stroke centers, and EDs with telestroke capabilities). The results underscore the investments that have been made in improving stroke systems of care and the valuable role of telestroke for addressing rural disparities in access.

(Summary submitted by Kori Sauser Zachrison, MD, MSc, FACEP, FAHA, Department of Emergency Medicine)

The Beirut port blast in August 2020 was the largest urban explosion since Hiroshima and Nagasaki. Shortly after, Mass General led the Beirut Blast Assessment for Surgical Services (BASS) collaborative across four of the largest Beirut hospitals to study the pattern of injuries and their management. Out of 1,818 patients, 30 died in the ED, 11 died during hospitalization, and 51 had long-term disability. Main lessons learned included: The importance of having key hospital functions (e.g., laboratory, operating room) underground; the non-adaptability of electronic medical records to disasters; the ED overwhelming with mild injuries, delay in arrival of the severely injured; and the need for realistic disaster drills.

(Summary submitted by Anthony Gebran, MD, Department of Surgery)

Higher adherence to one of four healthy dietary patterns consistent with the recommendations of the USDA’s 2020-2025 Dietary Guidelines for Americans significantly reduces the risk of new onset gout among women by 12%-32%. The healthy dietary patterns studied using prospectively collected data from the Nurses’ Health Study included the Dietary Approaches to Stop Hypertension (DASH), Mediterranean, Prudent, and Alternative Healthy Eating Index (AHEI) diets. On the contrary, high adherence to an unhealthy Western diet enriched with fatty and processed foods was associated with a 49% increased risk of new set gout among women. Many of the healthy dietary patterns included in this analysis have added cardiovascular benefits, such as lowering blood pressure or cholesterol. Therefore, women at risk of developing gout can choose from one of several dietary patterns according to their comorbidities and preferences to simultaneously reduce their cardiovascular and gout risk.

(Summary submitted by Chio Yokose, MD, Department of Medicine)

We generated a single-cell transcriptomic atlas of the intestinal stromal compartment in mice. We also identified inflammation-associated fibroblasts producing IL-11 and mucosa-associated fibroblasts expressing Adamdec1, which is required for tissue remodeling and healing during colitis.

(Summary submitted by Daniel Graham, PhD, Department of Medicine)

Depression is a leading cause of disability worldwide, but efforts to prevent depression have focused on a limited set of individual-level interventions. We studied a large cohort of individuals in a high-risk, low-income population followed over 10 years. We found that the availability of community-level social support infrastructure decreased the risk of incident depression by nearly 50%. This study suggests that investment in community-level social support can provide substantial benefit in preventing depression and improving population mental health.

(Summary submitted by Jordan W. Smoller, MD, ScD, Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine)

Allopurinol is a commonly used medication to lower serum urate (SU) for gout. However, two recent randomized clinical trials found that allopurinol potentially increased risk of death among patients with chronic renal disease (CKD) but without gout. Using a large primary care database from England we found that among patients with gout and CKD, initiation of allopurinol treatment was not associated with an increased risk of mortality, with the 5-year mortality rate being 4.9 and 5.8 per 100 person-years in 5,277 allopurinol initiators and 5,277 matched non-initiators. Neither “achieving target SU level” with allopurinol nor “allopurinol dose escalation” was associated with increased mortality. These findings provide reassurance that allopurinol does not have an apparent detrimental effect on mortality in patients with both gout and CKD.

(Summary submitted by Yuqing Zhang, DSc, Division of Rheumatology, Allergy, and Immunology, The Mongan Institute)

Variability of care for nursing home residents with advanced dementia is well documented but poorly understood. Black nursing home residents are often subject to the use of more aggressive interventions that often do not benefit nor comfort residents with advanced dementia. By interviewing 169 nursing home staff from 14 nursing homes, we were able to identify organizational factors and staff perceptions that result in variability in advanced dementia care under the following domains; implicit and explicit values, physical environment, care processes, and decision-making. This study revealed staff in all participating nursing homes had preconceptions towards the care of Black residents, and identified several factors that, if addressed, may reduce disparities and achieve equitable advanced dementia care.

(Summary submitted by Jenna Ryan Locke, MGH Institute of Health Professions)

The advent of a powerful new technology, the Neuropixels probe, provides a powerful high-resolution dynamic 'movie' of ongoing electrical dynamics of neural activity which we previously did not have access to. We arrived at two protocols for recording human brain activity using the Neuropixels probe. Following adjustments to the operating room environment, the researchers were able to record from 202 individually identifiable neurons in the human cortex using a single Neuropixels probe to be provide a blueprint for clinicians and researchers for how to implement the use of this device in the operating room and a powerful tool for studying human cognitive processes and their dysfunction at unprecedented spatiotemporal resolution.

(Summary submitted by Yangling Chou, PhD, Department of Neurology)

Press Releases

Suicidal Thoughts Can Help Identify Teens With a Variety of Treatable Psychosocial Problems
Featuring Juliana Holcomb

Study offers pediatricians new guidance for responding to suicidal ideation.

Researchers Restore Function in a Gene That Can Suppress Liver Cancer and Enhance Immunotherapy
Featuring Dan G. Duda, DMD, PhD

A team builds on COVID-19 mRNA vaccine technology to target specific pathways driving hepatocellular carcinoma.

COVID-19-Associated Strokes Link to Higher Disability and Death Risk
Featuring Adam A. Dmytriw, MD, MPH, MSc

During the first wave of the pandemic, patients with COVID-19 who experienced strokes caused by blockage of blood flow to brain tissues were more likely to die or have serious complications compared with non-infected stroke patients.

Study Shows Persistent Antibodies in Infants after COVID-19 Vaccination in Pregnancy
Featuring Andrea Edlow, MD, MSc, Alessio Fasano, MD

A study showed vaccination during pregnancy resulted in more lasting antibody levels in infants, when compared to babies born to unvaccinated, COVID-infected mothers.

In Helping Smokers Quit, Combining Treatments Is Key
Featuring Nancy Rigotti, MD

A new clinical review provides guidance to physicians and the public about the most effective tobacco cessation treatments.

Most People With Prior SARS-CoV-2 Infection or Vaccination Have T Cell Immune Responses Against Omicron Variant Despite Low Antibody Responses
Featuring Gaurav D. Gaiha, MD, Dphil

Booster vaccines can enhance T cell responses to help protect against severe COVID-19.

Researchers Devise Sex-cell Precursors With Staying Power
Featuring Toshi Shioda, MD, PhD

Scientists have developed a durable stand-in for human germ cell precursors that can be used to ethically study human development and reproductive tract cancers.

Knowledge of Racism’s Impact on Health Is Key for Physicians to Intervene, Study Finds
Featuring Sherri-Ann Burnett-Bowie, MD, MPH

A new study finds that while the majority of internal medicine faculty and trainees believe that racism has pernicious effects on health and society, fewer than half reported speaking out against racism they observed in the hospital. Education and creating safe spaces to discuss racism may increase individuals’ willingness to report racist behaviors and policies.

High-Resolution Probe May Help Unlock Secrets of Brain Function and Neurological Diseases
Featuring Angelique Paulk, PhD

The probe records activity of neurons in the human brain with unprecedented clarity and precision.

For Successful Hospital-at-Home Programs, Crucial Technologies Are Within Reach
Featuring Jared Conley, MD, PhD, MPH

Researchers offer lessons learned on employing the critical technologies to make hospital care at home more efficient and scalable.

Three-Drug Combination Prolongs Survival in Men With Metastatic, Hormone-sensitive Prostate Cancer
Featuring Matthew R. Smith, MD, PhD

A phase 3 trial demonstrates multiple benefits of adding the androgen-receptor inhibitor darolutamide to standard therapy.

Are Pandemic-Related Stressors Impacting Uninfected People’s Brain Health?
Featuring Marco L. Loggia, PhD

New study reveals that living through the COVID-19 pandemic may trigger brain inflammation that contributes to fatigue, concentration difficulties and depression.

Analysis Offers New Insights on the Placebo Effect and How to Harness Its Therapeutic Potential
Featuring Emiliano Santarnecchi, PhD

Researchers developed a “map” of brain regions activated by the placebo effect; several regions overlap with areas targeted by brain-stimulation therapy for depression. These findings have important implications for interpreting placebo-controlled clinical trial results and suggest that the placebo effect could be leveraged as a therapeutic tool.

Researchers Identify a Promising Drug for Treating Serious COVID-19 Complication in Children
Featuring Alessio Fasano, MD, Lael Yonker, MD

Study shows rapid improvement in children with MIS-C treated with drug first developed for celiac disease.

Newly Diagnosed Diabetes in Patients With COVID-19 May Simply Be a Transitory Form of the Blood Sugar Disorder
Featuring Sara Jane Cromer, MD, Deborah Wexler, MD, MSc

Researchers shed light on whether newly diagnosed diabetes in COVID-19 patients is truly new or merely previously undiagnosed

Engaging in Comprehensive Advance Care Planning Improves Participation Among Older Patients
Featuring Angelo Volandes, MD, MPH

New research shows that using a comprehensive approach to engage patients in Advance Care Planning (ACP) during the COVID-19 pandemic effectively improves the opportunity for ACP discussions and documentation as well as equitable healthcare delivery.

Adaptive HEALEY ALS Platform Trial Hopes to Bring New Treatments to Patients Faster
Featuring Merit Cudkowicz, MD, Sabrina Paganoni, MD, PhD

First-of-its-kind trial design expedites drug testing and expands patient access to new investigational products.

Do Hospitals That Conduct Research Provide Better Care for Patients?
Featuring David M. Shahian, MD

Analysis reveals that hospitals that publish research studies have lower patient mortality rates for numerous medical conditions and procedures, as well as higher patient satisfaction scores.

Blog Posts

Heart Health Month: Untangling the Connections Between Stress and Cardiovascular Disease

Featuring Michael Osborne, MD and Ahmed Tawakol, MD

Michael Osborne, MD, and Ahmed Tawakol, MD, are working to learn more about the connections between stress and heart disease, and to identify new treatment strategies.

Study Finds More Efforts Are Needed to Increase Diversity Among Cancer Clinicians

Featuring Sophia Kamran, MD

A new study highlights the need for more initiatives to ensure successful recruitment and retention of URM individuals throughout the academic promotional pipeline.

Heart Health Month: Looking to Nature for Better Ways to Preserve Donor Hearts
Featuring Shannon Tessier, PhD

Shannon Tessier, PhD, is drawing inspiration from nature to devise new strategies to preserve donor hearts for transplant.

Spike in Alcohol Consumption During COVID-19 Could Have Long-Term Health Consequences
Featuring Jagpreet Chhatwal, PhD

A simulation model projects a worrying rise in alcohol-related liver disease and death as a result of drinking increases during the COVID-19 pandemic.

Heart Health Month: How Cardiac Imaging Can Give Us a Better Understanding of Heart Failure
Featuring Christopher Nguyen, PhD

=Christopher Nguyen, PhD, is using advanced cardiac imaging to help develop new therapies for heart failure.

Heart Health Month: Reducing Health-Related Anxiety in Patients With Heart Disease
Featuring Ami Bhatt, MD

=Ami Bhatt, MD, is studying how resilience programs can help reduce anxiety in patients with cardiac disease.

Heart Health Month: Reducing the Risks for Pregnant Women With Heart Disease
Featuring Nandita Scott, MD

Nandita Scott, MD, and the team at the Corrigan Women's Heart Health Program are working to reduce the impact of cardiovascular diseases in pregnancy.

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Snapshot of Science for February 2022