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1
Otero, Tiffany M. N., D. Dante Yeh, Ednan K. Bajwa, Ruben J. Azocar, Andrea L. Tsai, Donna M. Belcher, and Sadeq A. Quraishi. "Elevated Red Cell Distribution Width Is Associated With Decreased Ventilator-Free Days in Critically Ill Patients." Journal of Intensive Care Medicine 33, no. 4 (June 1, 2016): 241–47. http://dx.doi.org/10.1177/0885066616652612.
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Introduction: Elevated red cell distribution width (RDW) is associated with mortality in a variety of respiratory conditions. Recent data also suggest that RDW is associated with mortality in intensive care unit (ICU) patients. Although respiratory failure is common in the ICU, the relationship between RDW and pulmonary outcomes in the ICU has not been previously explored. Therefore, our goal was to investigate the association of admission RDW with 30-day ventilator-free days (VFDs) in ICU patients. Methods: We performed a retrospective analysis from an ongoing prospective, observational study. Patients were recruited from medical and surgical ICUs of a large teaching hospital in Boston, Massachusetts. The RDW was assessed within 1 hour of ICU admission. Poisson regression analysis was used to investigate the association of RDW (normal: 11.5%-14.5% vs elevated: >14.5%) with 30-day VFD, while controlling for age, sex, race, body mass index, Nutrition Risk in the Critically Ill score, the presence of chronic lung disease, Pao2/Fio2 ratio, and admission levels of hemoglobin, mean corpuscular volume, phosphate, albumin, C-reactive protein, and creatinine. Results: A total of 637 patients comprised the analytic cohort. Mean RDW was 15 (standard deviation 4%), with 53% of patients in the normal range and 47% with elevated levels. Median VFD was 16 (interquartile range: 6-25) days. Poisson regression analysis demonstrated that ICU patients with elevated admission RDW were likely to have 32% lower 30-day VFDs compared to their counterparts with RDW in the normal range (incidence rate ratio: 0.68; 95% confidence interval: 0.55-0.83: P < .001). Conclusions: We observed an inverse association of RDW and 30-day VFD, despite controlling for demographics, nutritional factors, and severity of illness. This supports the need for future studies to validate our findings, understand the physiologic processes that lead to elevated RDW in patients with respiratory failure, and determine whether changes in RDW may be used to support clinical decision-making.
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Price, Donald L., Patrick D. Barnes, George A. Taylor, and C. D. Robson. "Radiologic-Pathologic Conference of Children's Hospital Boston: Pineal region mass in a neonate." Pediatric Radiology 27, no. 10 (October 14, 1997): 829–31. http://dx.doi.org/10.1007/s002470050247.
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Ecklund, Kirsten, G. A. Taylor, and Deborah H. Schofield. "Radiologic-Pathologic Conference of Children's Hospital Boston: Abdominal mass in a prepubertal girl." Pediatric Radiology 27, no. 10 (October 14, 1997): 832–34. http://dx.doi.org/10.1007/s002470050248.
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Paoletti, Leanne J., Jessica Bradford, and Lawrence C. Paoletti. "A Serotype VIII Strain among Colonizing Group B Streptococcal Isolates in Boston, Massachusetts." Journal of Clinical Microbiology 37, no. 11 (1999): 3759–60. http://dx.doi.org/10.1128/jcm.37.11.3759-3760.1999.
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Maternal colonization with group B Streptococcus (GBS) is a risk factor for neonatal GBS disease. Whereas serotypes Ia, Ib, II, III, and V are prevalent in the United States, types VI and VIII predominate in Japan. Recently, a serotype VIII strain was detected among 114 clinical GBS isolates from a Boston, Mass., hospital.
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Dwek, J. R., H. P. W. Kozakewich, and G. A. Taylor. "Radiologic-Pathologic Conference of Children's Hospital Boston: Chest wall mass in an infant with eczema." Pediatric Radiology 26, no. 2 (February 1996): 165–67. http://dx.doi.org/10.1007/bf01372101.
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Medina, L. S., Patrick D. Barnes, Michael J. Donovan, and George A. Taylor. "Radiologic-Pathologic Conference of Children's Hospital Boston: Intraconal mass in the orbit of an infant." Pediatric Radiology 27, no. 8 (August 18, 1997): 682–84. http://dx.doi.org/10.1007/s002470050211.
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Bloom, D. A., Deborah Schofield, and Fredric A. Hoffer. "Radiologic-Pathologic Conference of Children's Hospital Boston: A palpable pelvic mass in an adolescent girl." Pediatric Radiology 27, no. 11 (November 17, 1997): 888–91. http://dx.doi.org/10.1007/s002470050263.
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Robson, C. D., P. D. Barnes, M. L. Rodriguez, and G. A. Taylor. "Radiologic-Pathologic Conference of Children's Hospital Boston: Scalp mass in a child following treatment for craniopharyngioma." Pediatric Radiology 26, no. 3 (March 1996): 236–38. http://dx.doi.org/10.1007/bf01405308.
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Hojman, Horacio, Rishi Rattan, Rob Osgood, Mengdi Yao, and Nikolay Bugaev. "Securing the Emergency Department During Terrorism Incidents: Lessons Learned From the Boston Marathon Bombings." Disaster Medicine and Public Health Preparedness 13, no. 4 (March 12, 2019): 791–98. http://dx.doi.org/10.1017/dmp.2018.148.
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ABSTRACTTerrorist incidents that target hospitals magnify morbidity and mortality. Before a real or perceived terrorist mass casualty incident threatens a hospital and its providers, it is essential to have protocols in place to minimize damage to the infrastructure, morbidity, and mortality. In the years following the Boston Marathon bombings, much has been written about the heroic efforts of survivors and responders. Far less has been published about near misses due to lack of experience responding to a mass casualty incident resulting from terrorism. After an extensive review of the medical literature and published media in English, Spanish, and Hebrew, we were unable to identify a similar event. To the best of our knowledge, this is the first reported experience of a bomb threat caused evacuation of an emergency department in the United States while actively responding to multiple casualty terrorist incidents. We summarized the chronology of the events that led to a bomb threat being identified and the subsequent evacuation of the emergency department. We then reviewed the problematic nature of our response and described evidence-based policy changes based on data from health care, law enforcement, and counterterrorism. (Disaster Med Public Health Preparedness. 2019;13:791–798)
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Castro, Adham do Amaral e., Thelma Larocca Skare, Paulo Afonso Nunes Nassif, Alexandre Kaue Sakuma, and Wagner Haese Barros. "Sonographic diagnosis of carpal tunnel syndrome: a study in 200 hospital workers." Radiologia Brasileira 48, no. 5 (October 2015): 287–91. http://dx.doi.org/10.1590/0100-3984.2014.0069.
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AbstractObjective:To describe the prevalence of carpal tunnel syndrome in a sample of 200 healthy hospital workers, establishing the respective epidemiological associations.Materials and Methods:Two hundred individuals were submitted to wrist ultrasonography to measure the median nerve area. They were questioned and examined for epidemiological data, body mass index, carpal tunnel syndrome signs and symptoms, and submitted to the Boston carpal tunnel questionnaire (BCTQ) to evaluate the carpal tunnel syndrome severity. A median nerve area ≥ 9 mm2 was considered to be diagnostic of carpal tunnel syndrome.Results:Carpal tunnel syndrome was diagnosed by ultrasonography in 34% of the sample. It was observed the association of carpal tunnel syndrome with age (p < 0.0001), paresthesia (p < 0.0001), Tinel's test (p < 0.0001), Phalen's test (p< 0.0001), BCTQ score (p < 0.0001), and years of formal education (p < 0.0001). Years of formal education was the only variable identified as an independent risk factor for carpal tunnel syndrome (95% CI = 1.03 to 1.24).Conclusion:The prevalence of carpal tunnel syndrome in a population of hospital workers was of 34%. The number of years of formal education was the only independent risk factor for carpal tunnel syndrome.
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Dai, Jun, Yafen Guo, Quan Zhou, Xiang-Jie Duan, Jinhua Shen, and Xueqing Zhang. "The relationship between red cell distribution width, serum calcium ratio, and in-hospital mortality among patients with acute respiratory failure: A retrospective cohort study of the MIMIC-IV database." Medicine 103, no. 15 (April 12, 2024): e37804. http://dx.doi.org/10.1097/md.0000000000037804.
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To investigate the impact of RDW/CA (the ratio of red cell distribution width to calcium) on in-hospital mortality in patients with acute respiratory failure (ARF). This retrospective cohort study analyzed the data of 6981 ARF patients from the Medical Information Mart for Intensive Care (MIMIC-IV) database 2.0. Critically ill participants between 2008 and 2019 at the Beth Israel Deaconess Medical Center in Boston. The primary outcome of interest was in-hospital mortality. A Cox proportional hazards regression model was used to determine whether the RDW/CA ratio independently correlated with in-hospital mortality. The Kaplan–Meier method was used to plot the survival curves of the RDW/CA. Subgroup analyses were performed to measure the mortality across various subgroups. After adjusting for potential covariates, we found that a higher RDW/CA was associated with an increased risk of in-hospital mortality (HR = 1.17, 95% CI: 1.01–1.35, P = .0365) in ARF patients. A nonlinear relationship was observed between RDW/CA and in-hospital mortality, with an inflection point of 1.97. When RDW/CA ≥ 1.97 was positively correlated with in-hospital mortality in patients with ARF (HR = 1.554, 95% CI: 1.183–2.042, P = .0015). The Kaplan–Meier curve indicated the higher survival rates for RDW/CA < 1.97 and the lower for RDW/CA ≥ 1.97 after adjustment for age, gender, body mass index, and ethnicity. RDW/CA is an independent predictor of in-hospital mortality in patients with ARF. Furthermore, a nonlinear relationship was observed between RDW/CA and in-hospital mortality in patients with ARF.
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Naef, Andreas P. "Claude E. Welch, A twentieth-century surgeon. My life in the Massachusetts General Hospital. Boston, Mass., Massachusetts General Hospital, 1992. XX, 392 S. Illustr. Portr. $ 24.95. ISBN 0-88135-181-4." Gesnerus 50, no. 3-4 (November 25, 1993): 303–4. http://dx.doi.org/10.1163/22977953-0500304036.
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Ho, Peter T. C., Judy A. Estroff, Harry Kozakewich, Robert C. Shamberger, Craig W. Lillehei, Holcombe E. Grier, and Lisa Diller. "Prenatal Detection of Neuroblastoma: A Ten-Year Experience From the Dana-Farber Cancer Institute and Children's Hospital." Pediatrics 92, no. 3 (September 1, 1993): 358–64. http://dx.doi.org/10.1542/peds.92.3.358.
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Objectives. To assess the relative frequency of, the clinical and pathological correlates in, and the prognosis of the subset of infants with neuroblastoma who were identified initially by prenatal ultrasonography. Design. Retrospective review of all patients with neuroblastoma evaluated between 1982 and 1992. Setting. Large, urban, tertiary care children's hospital in Boston, Massachusetts. Patients. Eleven infants with neuroblastoma initially detected with prenatal sonograms were identified. Results. Nine patients had adrenal tumors; two had thoracic paraspinal tumors. Typical diagnostic evidence for neuroblastoma including a palpable abdominal mass and elevations in urinary catecholamines were not commonly seen postnatally. These patients had multiple favorable prognostic indicators including low stage of disease (10/11), favorable biological markers including cellular DNA content (5/5) and N-myc oncogene copy number (5/5), and histopathology suggestive for neuroblastoma in situ (7/11). All patients were treated by surgical resection. One patient exhibited progression of disease postoperatively, but demonstrated a complete clinical response to multiagent chemotherapy. Overall survival in our population was excellent with no deaths seen at a mean follow-up of 37 months (range 3 to 120 months). Conclusions. Patients with neuroblastoma identified by prenatal ultrasonography generally, although not exclusively, follow a clinically favorable course in which surgical resection is curative. Chemotherapy is not indicated unless substantial progression of disease occurs.
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Randolph, Judson. "Treatment of Mixed Tumors of the Kidney in Childhood, by Robert E. Gross, MD, and Edward B. D. Neuhauser, MD,Pediatrics, 1950;6:843–852." Pediatrics 102, Supplement_1 (July 1, 1998): 209–10. http://dx.doi.org/10.1542/peds.102.s1.209.
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This fundamental paper by a surgeon, Dr Gross, and a radiologist and radiotherapist, Dr Neuhauser, cleaned up the existing information and conflicting results of therapy for Wilms' tumor through 1947. There is a careful review of literature, comments about existing suggestions of preoperative radiation versus postoperative radiation versus radiation only and versus surgery without radiation. The authors then carefully analyze the experience at Boston Children's Hospital over the period from 1914 to 1947. This material is carefully broken down into three periods, 1914 to 1930, 1931 to 1939, and 1940 to 1947. During period I, 1914 to 1930, 27 cases of Wilms' tumor were seen and four cures were obtained for a survival rate of 14.9%. Beginning in 1931, under the able leadership of Dr William E. Ladd, a vigorous approach to the surgery for children with Wilms' tumor was undertaken. The program consisted of a wide transabdominal incision rather than the more classic approach to kidney surgery by a flank incision. This surgical exposure allowed prompt identification and control of the renal vessels and removal, in most cases, of the entire tumor and kidney mass without rupture of the encapsulated tumor. Additionally, Dr. Ladd insisted on careful fluid and blood replacement before and during surgery and a meticulous approach to the anesthestic management of the child undergoing surgery. In previous experience at Boston Children's and other reported centers, there had been a large number of intraoperative deaths. After 1932, there were no deaths from the surgery at Children's Hospital in Boston. In the 1931 to 1939 experience, 31 patients were operated on and ten cures were achieved for a survival rate of 32.2%. Beginning in 1940, Dr Gross and Dr Neuhauser instituted a program of immediate surgery and postoperative radiation to the bed of the tumor. Thirty-eight children were so treated with a survival rate of 47.3%. This group of patients was subsequently followed for 2½ years so that cures, recurrences, and deaths could be accurately reported. This patient material also emphasized that babies in the first 12 months of life had a far better outlook than did older subjects. The authors also emphasized that if recurrences were to occur, they were usually evident within 9 months after operative removal and radiation therapy. Postoperative radiation therapy was given in daily doses of 200r alternately using three portals, anteriorly, laterally, and posteriorly over the tumor bed reaching a total of 4000 to 5000r using a 200KV machine.
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Wagner, Cynthia, Sarah Marchina, Judith A. Deveau, Colleen Frayne, Kim Sulmonte, and Sandeep Kumar. "Risk of Stroke-Associated Pneumonia and Oral Hygiene." Cerebrovascular Diseases 41, no. 1-2 (November 20, 2015): 35–39. http://dx.doi.org/10.1159/000440733.
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Background: Pneumonia is a major complication of stroke, but effective prevention strategies are lacking. Since aspiration of oropharyngeal secretions is the primary mechanism for development of stroke-associated pneumonia, strategies that decrease oral colonization with pathogenic bacteria may help curtail pneumonia risk. We therefore hypothesized that systematic oral care protocols can help decrease pneumonia risk in hospitalized stroke patients. In this study, we investigated the impact of a systematic oral hygiene care (OHC) program in reducing hospital-acquired pneumonia in patients with acute-subacute stroke. Methods: This study compared the proportion of pneumonia cases in hospitalized stroke patients before and after implementation of a systematic OHC intervention. All patients hospitalized with acute ischemic stroke or intracerebral hemorrhage admitted to a large, urban academic medical center in Boston, Mass., USA from May 31, 2008, to June 1, 2010 (epoch prior to implementation of OHC), and from January 1, 2012, to December 31, 2013 (epoch after full implementation of OHC), who were 18 years of age and hospitalized for ≥2 days were eligible for inclusion. The cohort in the first epoch constituted the control group whereas the cohort in the second epoch formed the intervention group. Multivariate logistic regression was used to control for confounders. The main outcome measure was hospital-acquired pneumonia, defined via International Classification of Diseases, Ninth Revision, Clinical Modification codes. Results: The cohort comprised 1,656 admissions (707 formed historical controls; 949 were in the intervention group). The unadjusted incidence of hospital-acquired pneumonia was lower in the group assigned to OHC compared to controls (14 vs. 10.33%; p = 0.022) with an unadjusted OR of 0.68 (95% CI 0.48-0.95; p = 0.022). After adjustment for influential confounders, the OR of hospital-acquired pneumonia in the intervention group remained significantly lower at 0.71 (95% CI 0.51-0.98; p = 0.041). Conclusion: In this large hospital-based cohort of patients admitted with acute stroke, systematic OHC use was associated with decreased odds of hospital-acquired pneumonia.
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Gobishangar, Sreekanthan, Sundaramoorthy Iyer T. Sarma, and Suwaminathan Thiruvarangan. "Association between baseline characteristics of carpal tunnel syndrome and its relation to psychometric properties of the Boston carpal tunnel questionnaire." Journal of Musculoskeletal Surgery and Research 7 (November 6, 2023): 293–97. http://dx.doi.org/10.25259/jmsr_156_2023.
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Objectives: Carpal tunnel syndrome (CTS) generally causes functional disabilities and consequently develops socioeconomic burdens for individuals and our community in the long run. The negative consequences are more recorded in developing nations. Therefore, early addressing the disorder is essential to eliminate the negative impacts on any health-care system. Methods: This descriptive cross-sectional study was conducted on patients with CTS attending the professorial surgical clinics at Teaching Hospital Jaffna. The demographic and clinical presentation while a self-reported Boston Carpal Tunnel Questionnaire (BCTQ) was used to assess the severity of symptoms and functional status of the wrist and hand. Results: This study involved 63 respondents whose mean age and body mass index were 55.4 ± 12.4 years and 25.6 ± 3.1, respectively. The larger proportion was female (74.6%) and the majority’s civil status was married (90.5%). Menial and skilled jobs were 46.6% and 31.7%, respectively, whereas the remaining were professionals. The right-hand dominance was 93.7%, although 57.1% had the right hand affected. There was a significant association (r = 0.739 and P = 0.0001) between the clinical tests and the severity of symptoms score. Conclusion: This study outcomes of CTSs severity and functional status with the BCTQ recommend that this tool and its scales indicate the association between CTSs baseline characteristics and impairments resulting from CTS in the clinical context.
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Lowry, Kristen C., Judy A. Estroff, and Reza Rahbar. "The Presentation and Management of Fibromatosis Colli." Ear, Nose & Throat Journal 89, no. 9 (September 2010): E4—E8. http://dx.doi.org/10.1177/014556131008900902.
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We conducted a systematic chart review to identify all in-fants with fibromatosis colli who had been seen at Children's Hospital in Boston from January 1999 through December 2004. We found 7 such cases, which involved 4 boys and 3 girls, aged 1 to 3.5 weeks at presentation. We compiled information on each patient's birth history, presenting signs and symptoms, significant medical history, imaging findings, management, follow-up, and outcome. Six of the 7 patients presented with a neck mass, and the remaining patient presented with neck “fullness.” Five patients developed torticollis at some point. All patients were treated conservatively with physiotherapy. Five patients experienced a complete resolution of signs and symptoms, and the other 2 experienced improvement. Based on our findings, we recommend that early management of fibromatosis colli include observation and physiotherapy to prevent or reverse torticollis and the craniofacial asymmetry that can result. Similarly attractive is the opportunity that physiotherapy provides for parents to involve themselves in the care of their newborn. It is important, therefore, to quickly identify fibromatosis colli as such in order to avoid unnecessary expenditures of resources and to promptly begin conservative treatment.
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Laposata, Martha E., Michael Laposata, Elizabeth M. Van Cott, Dion S. Buchner, Mohammed S. Kashalo, and Anand S. Dighe. "Physician Survey of a Laboratory Medicine Interpretive Service and Evaluation of the Influence of Interpretations on Laboratory Test Ordering." Archives of Pathology & Laboratory Medicine 128, no. 12 (December 1, 2004): 1424–27. http://dx.doi.org/10.5858/2004-128-1424-psoalm.
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Abstract Context.—Complex coagulation test panels ordered by clinicians are typically reported to clinicians without a patient-specific interpretive paragraph. Objectives.—To survey clinicians regarding pathologist-generated interpretations of complex laboratory testing panels and to assess the ability of the interpretations to educate test orderers. Design.—Surveys were conducted of physicians ordering complex coagulation laboratory testing that included narrative interpretation. Evaluation of order requisitions was performed to assess the interpretation's influence on ordering practices. Setting.—Physicians ordering coagulation testing at a large academic medical center hospital in Boston, Mass, and physicians from outside hospitals using the academic medical center as a reference laboratory for coagulation testing. Outcome Measures.—Physician surveys and evaluation of laboratory requisition slips. Results.—In nearly 80% of responses, the ordering clinicians perceived that the interpretive comments saved them time and improved the diagnostic process. Moreover, the interpretations were perceived by ordering clinicians to help prevent a misdiagnosis or otherwise impact the differential diagnosis in approximately 70% of responses. In addition, interpretations appeared to be able to train the ordering clinicians as to the standard ordering practices. Conclusions.—The results demonstrate physician satisfaction with an innovative information delivery approach that provides laboratory diagnostic interpretation and test-ordering education to clinicians in the context of their daily workflow.
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Ilinski, Adrian, Kiana Mahdaviani, Michael Fishman, Michael Cassidy, and Naomi Ko. "Abstract P2-26-01: Prospective breast biopsy collection at an urban safety-net hospital serving a diverse patient population." Cancer Research 83, no. 5_Supplement (March 1, 2023): P2–26–01—P2–26–01. http://dx.doi.org/10.1158/1538-7445.sabcs22-p2-26-01.
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Abstract Background: Despite advances in breast cancer imaging, research and treatment, higher mortality among racial/ethnic minority and low-income populations persists. Consent and enrollment of diverse and vulnerable patients into breast cancer research is critical. Given this urgent need for diversity in breast cancer research, successful collection and banking of fresh biospecimens from diverse patients is key to ameliorating some of the cancer disparities. Given our access to a unique and vulnerable patient population, we developed and implemented a clinical information and biospecimen repository for patients evaluated in the breast radiology and breast oncology outpatient clinics at Boston Medical Center (BMC). Our goal was to consent patients for donation of percutaneous breast biopsy samples, surgical tissue, and blood to develop a breast cancer biospecimen bank. Our long-term goal is to provide high-yield human samples for translational research studies in breast cancer from a diverse and vulnerable patient population. Methods: We designed a multi-disciplinary team of clinical providers and basic science researchers to envision a breast cancer biospecimen bank for research. Key stakeholders were identified, workflow was arranged, IRB obtained, and research staff trained. Patients presenting with suspicious mass on breast imaging (BI-RADS 4C and 5 categories) were eligible to enroll. Two percutaneous biopsy cores were obtained for research at the time of ultrasound guided biopsy. We leveraged the Hematology Oncology translational research program at Boston Medical Center and pilot finding to launch the project. Results: Since initiation in April 2021, we approached 68 patients and consented 44, for a successful consent rate of 64.7%. Of the 44 patients consented, 22 (50.0%) identified themselves as Black/African American, 11 (25.0%) as White/Caucasian, 10 (22.73%) as Hispanic and 1 (2.27%) as Asian. Of all patients enrolled, 41 (93.2%) had a breast malignancy, of which 27 (70.7%) were hormone-sensitive and 7 (17.1%) were TNBC. Additionally, of the 44 patients on study, only 9 (20.4%) had commercial insurance or managed care plan on the day of the consent. In total, 84 percutaneous biopsy cores were collected from 42 patients. Corresponding surgical tissue, plasma, serum and PBMCs were also obtained. Conclusion: Our program demonstrates that the enrollment of diverse and vulnerable breast cancer patients onto cancer research is achievable. We successfully created a breast biopsy program to provide access to diverse human samples for breast cancer translational research studies. Currently this repository serves to address many ongoing translational projects to understand: 1) the gap in knowledge of inherent differences in tumor biology and tumor environment, 2) metabolic regulation in the breast cancer microenvironment, and 3) heterogeneity of tumors and its effects on clinical outcomes and microenvironment interactions. Citation Format: Adrian Ilinski, Kiana Mahdaviani, Michael Fishman, Michael Cassidy, Naomi Ko. Prospective breast biopsy collection at an urban safety-net hospital serving a diverse patient population [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-01.
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Power^, Phoebe C., Kevin X. Liu^, Susan N. Chi, Karen D. Wright, Karen J. Marcus, Daphne A. Haas-Kogan, David Ebb, Torunn I. Yock, Shannon M. MacDonald*, and Kee Kiat Yeo*. "GCT-14. TREATMENT APPROACH FOR METASTATIC INTRACRANIAL GERMINOMA: A MULTI-INSTITUTIONAL EXPERIENCE." Neuro-Oncology 26, Supplement_4 (June 18, 2024): 0. http://dx.doi.org/10.1093/neuonc/noae064.269.
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Abstract BACKGROUND Germinoma is the most common CNS germ cell tumor in children. Treatment with 24Gy craniospinal irradiation (CSI) with boost to 40Gy alone results in excellent survival irrespective of disease stage. For localized germinoma, recent studies have demonstrated the efficacy of neoadjuvant chemotherapy in decreasing the field/dose of radiation therapy (RT) needed for cure. For metastatic germinoma however, the optimal RT approach when combined with chemotherapy is unclear. Herein, we present our experience in treating patients with metastatic germinoma. METHODS We performed a retrospective, IRB-approved study of patients with metastatic germinoma diagnosed between 2001-2023 at Boston Children’s Hospital, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Mass General Hospital. Clinical features, treatment plan, and outcomes were collected and analyzed using the Kaplan-Meier method and Fisher’s exact test. RESULTS Twenty-eight patients with metastatic germinoma were identified. Median age at diagnosis was 15.9 years (range:6.2-25.9). Metastasis was intracranial in 20, craniospinal in three and CSF-only in five patients. Six patients received CSI only. Twenty-two patients received neoadjuvant chemotherapy and CSI. Median number of chemotherapy cycles was 4 (range:3-6). Seventeen patients had complete response, four patients had partial response, and one patient had progressive disease with chemotherapy. All patients went on to receive CSI, with median dose of 21Gy (range:18-36Gy) with median IF boost to 36Gy (range:30-51.6Gy). Median duration of follow-up was 11 years (range:0.3-25.3). There were no recurrences or deaths within the cohort. Analysis of long-term outcomes data revealed no significant differences in frequency of endocrinopathies, CNS vasculopathies, or memory loss between the doses of RT. CONCLUSIONS Our data show that neoadjuvant chemotherapy followed by CSI is associated with excellent overall survival in patients with metastatic germinoma. Importantly, our experience suggests that in combination with neoadjuvant chemotherapy, 21Gy CSI may be sufficient as a curative dose in this patient population.
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Galan, Mark, Young Bae Kim, and Jonathan L. Hecht. "Does Physiologic Breakdown Mask Significant Pathology in Endometrial Biopsies? A Retrospective Case-Control Study." Archives of Pathology & Laboratory Medicine 130, no. 12 (December 1, 2006): 1847–49. http://dx.doi.org/10.5858/2006-130-1847-dpbmsp.
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Abstract Context.—Adequacy criteria for endometrial biopsy samples do not exist. Objective.—To assess the sensitivity of endometrial sampling for detecting neoplasia in the setting of extensive glandular and stromal breakdown. Design.—Retrospective case-control study. Surgical pathology records between 1996 and 2005 at Beth Israel Deaconess Medical Center (Boston, Mass) were searched for endometrial samples with diagnoses containing the key words “menstrual” or “extensive breakdown.” Hospital records for these women were parsed for demographics, clinical indications, and follow-up with rebiopsy within 6 months. Age cutoffs enriched the population for women at higher risk for carcinoma. A control group, consisting of 2 age-matched control patients for each test patient, was also studied; each control patient had an endometrial sample taken within a 6-month period and was not diagnosed with extensive breakdown, menstrual endometrium, or neoplasia on initial sampling. Results.—Fifty-four cases were identified. The primary biopsy reports had benign descriptive diagnoses (ie, proliferative, secretory, polyp). Follow-up biopsies showed benign pathology in all cases and specific causes of bleeding—including polyp, leiomyoma, or endometritis—in 28 (52%) of 54. In the control group, neoplasia was found in 2 of the 108 follow-up biopsies. Only 5 other controls had specific diagnoses; all were polyps. Conclusions.—Extensive breakdown or menstrual-pattern endometrium may mask other specific benign pathologies but does not commonly mask cancer.
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Resnick, Cory M., Jason K. Middleton, Carly E. Calabrese, Karan Ganjawalla, and Bonnie L. Padwa. "Retropalatal Cross-Sectional Area Is Predictive of Obstructive Sleep Apnea in Patients With Syndromic Craniosynostosis." Cleft Palate-Craniofacial Journal 57, no. 5 (October 24, 2019): 560–65. http://dx.doi.org/10.1177/1055665619882571.
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Objective: There is a high rate of obstructive sleep apnea (OSA) in patients with syndromic craniosynostosis (SCS). Little is known about the airway anatomy in this population. The purpose of this study is to characterize the 3 dimensional (3D) upper airway in patients with SCS with and without OSA. Design: This is a retrospective study of patients with SCS treated at Boston Children’s Hospital from 2000 to 2015. Patients were divided into OSA and no-OSA groups based on polysomnography. Predictor variables included age, sex, body mass index (BMI), and 3D upper airway measurements. The primary outcome variable was the presence or absence of OSA. Secondary outcome variables were apnea–hypopnea index and oxygen saturation nadir. Descriptive and bivariate statistics were computed, and significance was set as P < .05. Results: There were 24 patients: 16 in the OSA group and 8 in the no-OSA group. The 2 groups did not differ significantly by age, BMI, or syndromic diagnosis. The presence of OSA was associated with a smaller minimum retropalatal cross-sectional area (minRPCSA; P < .001). In a logistic regression model controlling for age, sex, and upper airway length, minRPCSA was the primary predictor of OSA ( P ≤ .002). Receiver operating characteristic analysis determined minRPCSA = 55.3 mm2 to be the optimal diagnostic threshold for OSA, with sensitivity = 100% and specificity = 87.5% ( P < .001). Conclusion: A minRPCSA ≤55.3 mm2 is predictive of the presence of OSA in patients with SCS.
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Zapaishchykova, Anna, Divyanshu Tak, Zezhong Ye, Sridhar Vajapeyam, Ceilidh Smith, Kevin X. Liu, Hugo J. W. L. Aerts, et al. "IMG-06. IMAGING-BASED, TEMPORALIS MUSCLE THICKNESS AS A BIOMARKER IN CHILDREN WITH GLIOMAS." Neuro-Oncology 26, Supplement_4 (June 18, 2024): 0. http://dx.doi.org/10.1093/neuonc/noae064.343.
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Abstract BACKGROUND Sarcopenia, or lean muscle loss, causes morbidity and early mortality in pediatric cancer patients and survivors. Sarcopenic patients who are also obese have a particularly morbid metabolic condition that cannot be identified by body mass index (BMI) alone. Temporalis muscle thickness (TMT) on T1-weighted MRI provides a direct assessment of lean muscle mass. In this study, we determined how TMT was associated with nutritional and survival outcomes in children with gliomas using an automated deep-learning pipeline that calculates TMT on MRI and provides age-and sex-specific TMT percentiles (iTMT). METHODS We analyzed a cohort of 343 patients and 1,673 scans (244 low-grade gliomas(LGG) and 99 high-grade gliomas (HGG)) diagnosed between 2000-2023 at Boston Children’s Hospital/Dana-Farber Cancer Institute, who had linked longitudinal MRI and clinical data available. We calculated and compared age-adjusted iTMT, BMI, weight percentiles, and serum albumin. Sarcopenic obesity in glioma survivors was defined as sarcopenic iTMT (<5th %tile) and obese BMI (>95th %tile). RESULTS iTMT was significantly correlated with BMI (N=1,574 scans, Spearman r=0.34, p=4e-45) and weight (N=1,574 scans, r=0.21, p=1e-17), but not serum albumin (N=84 scans, r=-0.04, p=0.66) at any given time point. Of all patients, 113(36.4%) had sarcopenic obesity during at least one time point. For HGG patients, those with less than the median survival time (550 days) had significantly lower baseline iTMT (median: 6th %tile vs. 33rd %tile, p=0.01). For LGG patients, symptoms of malnutrition at diagnosis were associated with a trend toward lower iTMT (N=244, 19th %tile vs.28th %tile, p=0.07). CONCLUSION Our study demonstrates that iTMT is an independent biomarker for malnutrition and survival for pediatric gliomas and can identify patients with sarcopenic obesity. iTMT assessment on routine clinical MRI could be a practical way to monitor muscle status and guide supportive interventions in children with brain tumors.
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Lee-Lewandrowski, Elizabeth, Daniel Corboy, Kent Lewandrowski, Julia Sinclair, Steven McDermot, and Theodore I. Benzer. "Implementation of a Point-of-Care Satellite Laboratory in the Emergency Department of an Academic Medical Center." Archives of Pathology & Laboratory Medicine 127, no. 4 (April 1, 2003): 456–60. http://dx.doi.org/10.5858/2003-127-0456-ioapsl.
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Abstract Context.—Emergency department (ED) overcrowding has reached crisis proportions in the United States. Many hospitals are seeking to identify process reengineering efforts to reduce crowding and ED patient length of stay (LOS). Objectives.—To investigate the impact of a point-of-care testing (POCT) satellite laboratory in the ED of a large academic medical center. Setting.—The ED of the Massachusetts General Hospital, Boston, Mass. Design and Outcome Measures.—Evaluation of physician satisfaction, turnaround time (TAT), and ED LOS before and after implementation of a POCT laboratory. ED LOS was measured by patient chart audits. TAT was assessed by manual and computer audits. Clinician satisfaction surveys measured satisfaction with test TAT and test accuracy. Results.—Blood glucose, urine human chorionic gonadotropin, urine dipstick, creatine kinase–MB, and troponin tests were performed in the ED POCT laboratory. Test TAT declined an average of 87% after the institution of POCT. The ED LOS decreased for patients who received pregnancy testing, urine dipstick, and cardiac markers. Although these differences were not significant for individual tests, when the tests were combined, the decreased LOS was, on average, 41.3 minutes (P = .006). Clinician satisfaction surveys documented equivalent satisfaction with test accuracy between the central laboratory and the POCT laboratory. These surveys also documented dissatisfaction with central laboratory TAT and increased satisfaction with TAT of the POCT program (P < .001). Conclusions.—The POCT satellite laboratory decreased test TAT and decreased ED LOS. There was excellent satisfaction with test accuracy and TAT.
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Yeo, Dannel, Vera Klemm, Payal Saxena, Althea Bastian, Heidi Strauss, Charbel Sandroussi, Sara Wahlroos, Peter Grimison, and John E. J. Rasko. "Abstract C011: Detection of circulating tumor cells for the early detection of pancreatic cancer." Cancer Research 84, no. 2_Supplement (January 16, 2024): C011. http://dx.doi.org/10.1158/1538-7445.panca2023-c011.
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Abstract Introduction The majority of pancreatic cancer patients are diagnosed with advanced, metastatic disease. Biomarkers to detect pancreatic cancer at earlier stages could drastically improve the poor survival rates. Circulating tumor cells (CTCs) are tumor cells that disseminate or are shed into the vascular system and have been detected in patients at pre-malignant stages. However, detecting these rare cells accurately and reliably remains a challenge. The AccuCyte-CyteFinder system uses density-based enrichment of blood nucleated cells followed by detection of CTCs using fluorescence staining, whole slide scanning and automated image analysis. This study aimed to examine whether CTCs could be used to identify patients with pancreatic lesions likely to malignant. Methods 50 patients undergoing an endoscopic ultrasound procedure for a pancreatic mass were recruited at the Royal Prince Alfred Hospital, Sydney, Australia or Chris O’Brien Lifehouse, Sydney, Australia. Peripheral blood was collected prior to the procedure and processed for CTCs on the AccuCyte-CyteFinder platform using a CK+ EpCAM+ CD45- staining panel. Results 28% (14/50) were found to have an intraductal papillary mucinous neoplasm (IPMN), 10% (5/50) pancreatic ductal adenocarcinoma (PDAC), 6% (3/50) pancreatic neuroendocrine tumor (PNET), 42% (21/50) non-neoplastic pancreatic cyst, and 14% (7/50) normal (no mass found). CTCs were highest in the PDAC group with an average of 5 cells/ml, followed by the IPMN (3 cells/ml), pancreatic cyst (2.5 cells/ml), and PNET (0 cells/ml). 86% (12/14) of IPMN patients had detectable CTCs. 2 IPMN patients with CTC counts of more than 5 cells/ml resulted in a resected sample having high-grade dysplasia while 3 IPMN patients with no/low CTC counts resulted in a resected sample having low-grade dysplasia. There was no correlation with the size of the pancreatic mass and CTC number. Conclusions CTCs could be detected in patients with pre-malignant pancreatic cancer and could determine malignancy. CTCs could potentially be used to detect pancreatic cancer early however, larger patient numbers and longer follow-up are required to validate these findings. Citation Format: Dannel Yeo, Vera Klemm, Payal Saxena, Althea Bastian, Heidi Strauss, Charbel Sandroussi, Sara Wahlroos, Peter Grimison, John E.J. Rasko. Detection of circulating tumor cells for the early detection of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C011.
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Jernigan, Sarah C., Jay G. Berry, Dionne A. Graham, Stuart B. Bauer, Lawrence I. Karlin, Nedda M. Hobbs, R. Michael Scott, and Benjamin C. Warf. "Risk factors of sudden death in young adult patients with myelomeningocele." Journal of Neurosurgery: Pediatrics 9, no. 2 (February 2012): 149–55. http://dx.doi.org/10.3171/2011.11.peds11269.
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Object Although survival for patients with myelomeningocele has dramatically improved in recent decades, the occasional occurrence of sudden, unexplained death in young adult patients with myelomeningocele has been noted by the authors. This study was undertaken to determine risk factors for sudden death in this population. Methods The authors performed a retrospective chart review of patients born between 1978 and 1990 who received care at Children's Hospital Boston. The relationship between sudden death and patient demographics, presence of CSF shunt and history of shunt revisions, midbrain length as a marker for severity of hindbrain malformation, seizures, pulmonary and ventilatory dysfunction, body mass index, scoliosis, renal dysfunction, and cardiac disease was evaluated using the t-test, Fisher exact test, and logistic regression analysis. Results The age range for 106 patients in the study cohort was 19–30 years, with 58 (54.7%) women and 48 (45.3%) men. Six patients, all of whom were young women, experienced sudden death. In multivariate analysis, female sex, sleep apnea, and midbrain elongation ≥ 15 mm on MR imaging remained significantly associated with a higher risk of sudden death. These risk factors were cumulative, and female patients with sleep apnea and midbrain length ≥ 15 mm had the greatest risk (adjusted risk ratio 24.0, 95% CI 7.3–79.0; p < 0.05). No other comorbidities were found to significantly increase the risk of sudden death. Conclusions Young adult women with myelomeningocele are at significantly increased risk of sudden death in the setting of midbrain elongation and sleep apnea. Further investigation is needed to determine the benefit of routine screening to identify at-risk patients for closer cardiopulmonary monitoring and treatment.
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Mack, J. W., E. F. Cook, J. Wolfe, H. E. Grier, P. D. Cleary, and J. C. Weeks. "Understanding of prognosis among parents of children with cancer: Parental optimism and the role of the parent-physician interaction." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 6033. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.6033.
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6033 Background: Patients often overestimate their chances of surviving cancer. Factors that contribute to accurate understanding of prognosis among parents of children with cancer are not known. Methods: We conducted a cross-sectional survey of 194 parents of children with cancer (overall response rate 70%), treated at the Dana-Farber Cancer Institute and Children’s Hospital, Boston, Mass, and the children’s physicians. Our main outcome measure was agreement between parent and physician ratings of the child’s likelihood of cure. Results: The majority of parents (61%) were more optimistic about the likelihood of their child’s cure than their child’s physician was. Most parents, however, believed that their opinions about prognosis either matched (70%) or were more pessimistic (26%) than those of their physicians. When physicians were confident in their knowledge of the child’s prognosis, parent and physician perceptions of prognosis were more likely to agree (OR 2.55, P = .004). Parents whose role in decision-making matched their ideal role were more likely to give prognostic estimates that agreed with physician perceptions of prognosis (OR 1.89, P = .019). In contrast, parent confidence in knowledge (OR .07, P < .0001), coping strategies (disengagement, OR .31, P = .007; reliance on emotional support from others, OR .31, P = .029), and use of intuition to understand prognosis (OR .51, P = .012), were associated with overestimation of likelihood of cure. Conclusions: Many parents overestimate their children’s chances of being cured of cancer. Neither physician nor parent attributes alone account for this finding; rather, successful communication about prognosis requires that physicians relate to parents’ individual communication and decision-making needs. No significant financial relationships to disclose.
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Zhu, Jia, Henry A. Feldman, Christine Chordas, Ari J. Wassner, Peter E. Manley, and Laurie E. Cohen. "Undernutrition and Pubertal Timing in Female Survivors of Medulloblastoma and Other Embryonal Tumors." Journal of Clinical Endocrinology & Metabolism 105, no. 10 (July 24, 2020): e3650-e3659. http://dx.doi.org/10.1210/clinem/dgaa475.
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Abstract Context Children with brain tumors may have pubertal onset at an inappropriately young chronologic age. Hypothalamic-pituitary irradiation ≥18Gy has been found to be a risk factor; age at irradiation is associated with pubertal timing. However, the underlying mechanisms are unknown. Objective To determine the impact of body mass index (BMI) and catch-up growth on pubertal timing in females treated for medulloblastoma and other embryonal tumors. Design, Setting, and Patients Retrospective cohort analysis of 90 female patients treated for medulloblastoma and other embryonal tumors at Dana-Farber Cancer Institute/Boston Children’s Hospital from 1996 to 2016. Eighteen individuals met inclusion criteria, with a mean ± SD follow-up period of 11.9 ± 3.4 years. Main Outcome Measures Multiple linear regression models for age at pubertal onset and bone age discrepancy from chronologic age at pubertal onset assessed the joint influences of age at irradiation, hypothalamic irradiation dose, undernutrition duration, BMI standard deviation score (SDS) at pubertal onset, and catch-up BMI SDS. Results The mean ± SD age of pubertal onset was 9.2 ± 1.3 years and hypothalamic radiation dose was 31.9 ± 9.9 Gy. There was a direct relationship between age at irradiation and age at pubertal onset (β = 0.323 ± 0.144 [standard error] year per year; P = 0.04) that was significantly attenuated after adjusting for BMI SDS at pubertal onset (P = 0.5) and catch-up BMI SDS (P = 0.08), suggesting that BMI is a mediator. Conclusions Both absolute and catch-up BMI SDS at pubertal onset are significant mediators of pubertal timing and bone age discrepancy in pediatric medulloblastoma and other embryonal tumors, and thus, are targetable risk factors to optimize pubertal timing.
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Okereke, Olivia, Vivian Anable Eme, Keliane Totten, Joseph Locascio, Alison Simmons, Nancy Carpenter, and Anthony Weiner. "A STAKEHOLDER-PARTNERED APPROACH TO INEQUITIES AFFECTING HOME HEALTH CARE WORKERS, OLDER ADULTS, AND CAREGIVERS." Innovation in Aging 7, Supplement_1 (December 1, 2023): 549. http://dx.doi.org/10.1093/geroni/igad104.1802.
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Abstract Home health aides (HHAs) provide on-site support for homebound older adults with cognitive impairments, while lessening strain on familial caregivers. However, HHAs face structural challenges in work-related transportation. Massachusetts General Hospital (MGH) researchers partnered with community and corporate stakeholders to inform a study evaluating whether on-demand transportation for HHAs via Uber rides will: 1) Improve metrics among HHAs (total visits, total unique patients, hours/week and days/week worked, missed visit/no-show rates, work satisfaction); 2) Increase racial, ethnic, socioeconomic and geographic diversity of older adults with cognitive impairments receiving homecare. Community partner CCHERS (Center for Community Health Education Research Services) helps residents of public/publicly-assisted housing in high-need areas of Greater Boston gain training and entry-level employment in healthcare as HHAs. Through its collaborations with other groups (e.g., Mothers for Justice & Equality, HomeCare Aide Council, Mass HomeCare Alliance), CCHERS identified that lack of affordable, accessible, reliable transportation was among the most-cited barriers affecting HHAs and equitable homecare delivery. Corporate partner Uber Health, through work in preliminary social-impact case studies, identified the platform’s central ride-coordination approach as preferred by Black and Hispanic women in the 18-45y age group (~80% of the local HHA workforce). MGH researchers’ study goals and metrics were informed by input of partners. With its community-engaged approach, innovative partnerships, and focus on achieving equity objectives to benefit patients and homecare workers alike, this project has potential for strong local impacts and future implications for state and/or national policies to provide high-quality, equitable homecare by directly addressing employment transportation-related barriers.
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Dashti, H. S., B. Cade, G. Stutaite, R. Saxena, S. Redline, and E. Karlson. "1164 Prospective Associations Between Sleep Duration, Variability and Timing and Diseases from an Electronic Health Record Biobank in 24,065 Individuals." Sleep 43, Supplement_1 (April 2020): A444—A445. http://dx.doi.org/10.1093/sleep/zsaa056.1158.
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Abstract Introduction Implementation of electronic health records (EHR) across healthcare systems linking clinical to survey data has enabled systematic assessments of longitudinal relationships between sleep traits and diseases classified by PheWAS codes where ICD-9/10 codes are collapsed to categories based on clinical similarity. In the Partners Biobank, a hospital-based virtual cohort from Mass General Brigham in greater Boston, MA, we aimed to assess associations between sleep traits and incident diseases. Methods Self-reported weekday/weekend bed and wake times from a survey at consent were used to derive sleep traits. Incident diseases were defined as two incident PheWAS codes on separate dates ≥1y after consent. Cox proportional hazards models compared short (<7h) and long (≥9h) sleep duration, with 7-8h (referent group), adjusted for age, gender, race/ethnicity, and employment status, then further adjusted for BMI. Similarly, sleep midpoint (midpoint between weekend wake/bed times), sleep debt (difference in weekend/weekday sleep duration), and social jetlag (difference in weekend/weekday sleep midpoint) were assessed. Results The analytical sample consisted of 24,065 adults (mean sleep duration =8.12h) seeking regular care with sleep data. Participants had a total of 7,513,649 ICD codes of which incident 323,946 ICD codes mapped to 137,137 PheWAS codes. Over a median follow-up of 2.73 years (interquartile range: 1.82-3.98), participants sleeping <7h had a significantly higher risk of incident Acute pain [hazard ratio(95% confidence interval)=1.46(1.2-1.78)], Tobacco use disorder [1.42(1.18-1.71)], Sciatica [1.72(1.3-2.27)], and Edema [1.69(1.25-2.28)]. Each additional hour of later sleep midpoint and increased sleep debt and social jetlag associated with higher risk of incident Major depressive disorder [midpoint:1.30(1.14-1.49); debt:1.23(1.09-1.38); jetlag:1.54(1.27-1.84)]. Associations retained significance upon further adjustment for BMI, except for Edema, and no other associations were observed at the Bonferroni threshold (P=0.0125). Conclusion Our findings in a large hospital-based virtual cohort support unique inter-relationships between sleep duration/timing on somatic, behavioral, and mental health outcomes. Support H.S.D. and R.S. are supported by NIDDK grant R01DK107859. B.C. is supported by K01-HL135405-01. S.R. and R.S. are partially supported by R35 NHLBI HL 135816.
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See, Alfred Pokmeng, Louise E. Wilkins-Haug, Carol B. Benson, Wayne Tworetzky, and Darren B. Orbach. "Percutaneous transuterine fetal cerebral embolisation to treat vein of Galen malformations at risk of urgent neonatal decompensation: study protocol for a clinical trial of safety and feasibility." BMJ Open 12, no. 5 (May 2022): e058147. http://dx.doi.org/10.1136/bmjopen-2021-058147.
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IntroductionAlthough endovascular techniques have improved outcomes in vein of Galen malformations (VOGM), there is still a high rate of morbidity and mortality, particularly among cases with decompensation in the neonatal period. The dimension of the draining venous sinus on fetal imaging correlates with the risk of neonatal decompensation. In fetuses within this high-risk group who do not have end-organ injury, there is a theoretical therapeutic opportunity to reduce the arteriovenous shunt before the normal physiological changes of birth precipitate decompensation. This study investigates the safety and potential benefit of treating a VOGM in utero, which has not been previously studied.Methods and analysisThis study aims to enroll 20 subjects: pregnant women with a fetus harbouring a high-risk VOGM (defined on MRI by a narrowest medial-lateral width greater than 8 mm in the draining venous sinus). Unfortunately, the subset of fetuses with in utero end-organ injury is ineligible, because the late stage of pathology is not amenable to recovery from a cerebrovascular intervention, likely not even in utero. This study aims to alter the physiology before such developments accrue.At or after 23 weeks of gestation, a transuterine transposterior fontanelle needle puncture to the torcular allows ultrasound-guided deployment of coils to embolise the draining venous malformation.This study has 97.5% power to detect major safety events at 30% or greater, and 80% power to detect a reduction in the rate of neonatal intervention from 80% to 30%. In the staged study design, an interval evaluation after 11 patients invokes study termination if safety events occur above the allowed threshold.Ethics and disseminationThe institutional review boards at Mass General Brigham and Boston Children’s Hospital (BCH) reviewed and approved this protocol. The BCH Department of Radiology and a patient family philanthropic donation fund this study. The trial results will be published in peer-reviewed journals and presented at scientific conferences.Trial registration numberNCT04434729
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Mack, J. W., E. F. Cook, J. Wolfe, H. E. Grier, P. D. Cleary, and J. C. Weeks. "Hope and prognostic disclosure." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 6510. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.6510.
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6510 Background: Physicians sometimes selectively convey prognostic information to support patients’ hopes. However, the relationship between prognostic disclosure and hope is not known. Methods: We surveyed 194 parents of children with cancer (overall response rate 70%) in their first year of cancer treatment at the Dana-Farber Cancer Institute and Children’s Hospital, Boston, Mass, and the children’s physicians. We evaluated relationships between parents’ recall of prognostic disclosure by the physician and the extent to which physician communications “always” made them feel hopeful. A five-item index of prognostic disclosure assessed whether prognostic information was provided in any form, in quantitative terms, and in written form, whether the physician gave prognostic information before the parent asked, and whether parents wanted additional prognostic information beyond what they had already received. Results: Parents were less likely to report hopeful communication when the child’s likelihood of cure was low (OR .70 per category of decreasing likelihood of cure, P=.0003). However, parents who reported having received more extensive prognostic information were more likely to report hopeful communication, even when the prognosis was poor. In a multivariable model, parental report that physician communication “always” made them feel hopeful was associated with increased prognostic disclosure (OR 1.67 per element of disclosure, P=.009) and higher perceived communication quality (OR 5.39, P<.0001). In contrast, communication-related hope was inversely associated with the child’s likelihood of cure (OR .67, P=.006). Conclusions: Although physicians sometimes selectively convey prognostic information to preserve hope, we found no evidence that prognostic disclosure makes parents less hopeful. Instead, disclosure of prognosis by the physician can support hope for parents of children with cancer, even when the child’s prognosis is poor. No significant financial relationships to disclose. [Table: see text]
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Healey, Elizabeth A., Patrick D. Barnes, William J. Kupsky, Michael R. Scott, Stephen E. Sallan, Peter McL Black, and Nancy J. Tarbell. "The Prognostic Significance of Postoperative Residual Tumor in Ependymoma." Neurosurgery 28, no. 5 (May 1, 1991): 666–72. http://dx.doi.org/10.1227/00006123-199105000-00005.
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Abstract Between 1970 and 1989, 29 patients with intracranial ependymomas were evaluated and treated at the Children's Hospital in Boston. With a median follow-up of 82 months, the actuarial survival rates at 5 and 10 years were 61 ± 10% and 46 ± 12%, respectively. Anaplastic histological findings were uncommon (2 of 29). Initial postoperative radiotherapy was given to 25 patients, with a median tumor dose of 5360 cGy. With a median time to recurrence of 22 months, local failure (within 2 cm of original enhancing mass) was the predominant pattern of relapse (15 of 16 failures). The presence of radiographic residual disease seen on postoperative magnetic resonance imaging or computed tomographic scans was the most important prognostic variable for patients with intracranial ependymoma. Analysis of the 19 patients who underwent postoperative imaging revealed a 75 ± 15% 5-year freedom from progressive disease for 9 patients with no residual disease. as compared with 0% freedom from progressive disease for the 10 patients with gross residual disease (P = 0.03). In contrast, the surgical assessment of residual disease was not significant (P = 0.4). Age at presentation was also a significant prognostic factor. The overall actuarial survival rate at 12 years for infants 24 months or younger at diagnosis was 0%, as compared with 62 ± 13% for older patients (P = 0.03). For non-anaplastic ependymomas, complete surgical resection followed by local-field, high-dose (>54 Gy) radiotherapy appears to offer the greatest chance for long-term survival. Because of the markedly reduced survival rate for patients with radiologically apparent postoperative disease, maximal surgical resection and novel therapeutic endeavors appear warranted for this high-risk group. Future protocols should use postoperative imaging, not operative reports, to stratify patients with ependymoma.
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Wollborn, Laura, James W. Webber, Sudhanshu Mishra, Chad B. Sussman, Cameron E. Comrie, Daniel G. Packard, Allison Vitonis, et al. "Abstract B044: Serum miRNA expression in ovarian cancer patients is independent of histological subtype and FIGO stage." Cancer Research 84, no. 5_Supplement_2 (March 4, 2024): B044. http://dx.doi.org/10.1158/1538-7445.ovarian23-b044.
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Abstract Background: Serum miRNAs have been proposed as potential biomarkers for the early detection of ovarian cancer (OC). The heterogenous histological subtypes of ovarian cancer show different morphologic and genetic alterations influencing outcome and survival. We aimed to evaluate if serum miRNA levels differ with histological OC subtype and FIGO stage. Methods: We included women with histological confirmed OC from three study sets: 36 specimens from the Mass General Brigham Biobank collected between 2012 and 2019, 51 specimens from women in the pelvic mass study treated at the Brigham and Women’s Hospital (BWH) or Massachusetts General Hospital (MGH) between 1998 and 2009 and 93 specimens from Aspira Women’s Heath collected between 2007 and 2012. Data from 1790 women without OC from the Mass General Brigham Biobank collected between 2012 and 2019 were used as controls. Serum levels of a focused panel of 179 circulating miRNAs were measured by flow cytometry using the Abcam Fireplex® assay. Differences in miRNA serum profiles were analyzed according to histological subtypes and early (FIGO stage I/II) vs. late stages (FIGO stage III/IV) by univariate analysis, adjusting for multiple comparisons using Bonferroni correction. Results: The study population of OC patients showed a median age range of 50-59 years and 70.2% were postmenopausal, while women in the control group were younger (median age range of 40-49 years) and 48.3% were postmenopausal. Among the study subjects, most OC were of epithelial origin (174 OC (96.1%)) and consisted of the following histological subtypes: 87 (48.1%) serous, 29 (16.0%) endometrioid, 15 (8.3%) clear cell, 18 (9.9%) mucinous, 1 (0.6%) transitional cell, 24 (13.3%) other epithelial OC, and 7 (3.9%) non-epithelial OC. Most patients were diagnosed with advanced stage disease (59.1%) and showed a high-grade histology (59.7%). Univariate analysis showed significant changes in circulating miRNA profiles for epithelial OC compared to the control group with significant changes in 133/179 miRNAs (corrected p<0.05). No significant changes in miRNA expressions were detected comparing serous vs. non-serous epithelial OC and comparing any histological epithelial subtype (serous, endometrioid, clear cell or mucinous OC) to all other OCs in the study population. Further sub-group analyses comparing early vs. late-stage OCs among serous epithelial and non-serous epithelial OC did not reveal any significant differences in miRNA profiles, either. Conclusion: Ovarian cancers show a distinct miRNA profile, but different histological epithelial OC subtypes and tumor stages cannot be distinguished by miRNA expression levels. Detection of OC by miRNAs as potential biomarkers can be performed independent of histological subtype and tumor stage. Citation Format: Laura Wollborn, James W. Webber, Sudhanshu Mishra, Chad B. Sussman, Cameron E. Comrie, Daniel G. Packard, Allison Vitonis, Stephanie Alimena, Ryan Phan, Todd Pappas, Daniel W. Cramer, Dipanjan Chowdhury, Kevin M. Elias. Serum miRNA expression in ovarian cancer patients is independent of histological subtype and FIGO stage [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B044.
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Leon, Armando R., Seena Koshy, Pablo Perez, Sucely Garcia, Nancy Sandoval, Francisco M. Marty, Johanna Samayoa, and Sophia Koo. "711. A Unique Breath Secondary Metabolite Volatile Signature for the Diagnosis of Histoplasmosis." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S454—S455. http://dx.doi.org/10.1093/ofid/ofab466.908.
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Abstract Background Histoplasmosis is a common endemic fungal infection in the Americas, causing significant morbidity and mortality, particularly in immunocompromised patients. Existing diagnostic methods are limited in their sensitivity (especially in pulmonary histoplasmosis) and turnaround time. Methods We examined prospectively collected breath samples from 84 patients with suspected histoplasmosis 3/2019 - 2/2020 at Hospital Roosevelt (HR; Guatemala City, Guatemala, n = 56) and suspected invasive fungal disease 1/2018 - 10/2019 at Brigham and Women’s Hospital (BWH; Boston, MA, USA, n = 28) using thermal desorption gas chromatography-tandem mass spectrometry (TDU-GC-MS/MS). Patients were evaluated for histoplasmosis and other infections according to the local standard of care – of note, 18/56 patients at HR did not have Histoplasma urine antigen testing. Results Median age was 44 years, 60 (71%) were male, 23 (27%) had HIV, 15 (18%) had hematologic malignancy. 7 patients were diagnosed with histoplasmosis over the study period (4 at HR, 5 at BWH), with a clinical syndrome + positive Histoplasma urine or serum antigen test, with some patients also having yeast forms on tissue biopsy. 3 patients had disseminated and 4 pulmonary histoplasmosis. 4 patients with histoplasmosis had co-infections – 2 tuberculosis (TB), 1 influenza, and 1 Pneumocystis jirovecii (PJP) pneumonia. 4 patients were receiving antifungal therapy active against Histoplasma at the time of their first breath sample. We found 3 sesquiterpenes: (A) cyperene, (B) 1R,4aR,8aR)-2,5,5,8a-Tetramethyl-4,5,6,7,8,8a-hexahydro-1H-1,4a-methanonaphthalene, and (C) viridiflorol in patients with histoplasmosis, that distinguished these patients from those with other pneumonia (TB, coccidioidomycosis, invasive aspergillosis, mucormycosis, PJP, bacterial pneumonia) with 100% sensitivity and 70% (95% CI 59, 80) specificity. Figure 1. TDU GC-MS/MS spectral comparison in histoplasmosis vs. the other invasive mycoses aspergillosis or mucormycosis. A: Cyperene; B: (1R,4aR,8aR)-2,5,5,8a Tetramethyl-4,5,6,7,8,8a-hexahydro-1H-1,4a-methanonaphthalene; C: viridiflorol; D: 1H-Indene, 2,3,3a,4-tetrahydro-3,3a,6-trimethyl-1-(1-methylethyl)-; E: β-funebrene; F: trans-α-bergamotene; G: eremophilene; H: spathulenol; I: cedrene; J: cedranoxide, 8,14- Conclusion Conclusion: Patients with histoplasmosis have a unique secondary metabolite breath signature that can be used for the noninvasive diagnosis of pulmonary and disseminated histoplasmosis. Many patients in this cohort did not undergo urine antigen testing or other diagnostic workup for histoplasmosis, which may have affected our specificity estimates. Disclosures Francisco M. Marty, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator)
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Gross, Bradley A., Edward R. Smith, and R. Michael Scott. "Cavernous malformations of the basal ganglia in children." Journal of Neurosurgery: Pediatrics 12, no. 2 (August 2013): 171–74. http://dx.doi.org/10.3171/2013.5.peds1335.
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Object Cavernous malformations (CMs) of the basal ganglia are relatively rare lesions that can lead to considerable neurological impairment because of their eloquent location. The authors reviewed the clinical course and surgical outcome of a series of children with basal ganglia CMs. Methods The authors retrospectively reviewed the operative experience of the senior author (R.M.S.) and the 1997–2011 database of Boston Children's Hospital for children with CM of the basal ganglia (which includes CM of the caudate and/or lentiform nucleus and excludes CM of the thalamus). They evaluated baseline demographics, presenting signs, operative outcomes, and condition at long-term follow-up visits and compared these characteristics among patients who underwent surgery and those who were observed. Results Of 180 children with a diagnosis of CM, 11 (6%) had CM of the basal ganglia. The mean age at diagnosis was 9.3 years, and the male/female ratio was 1.8:1. Presenting signs were as follows: hemorrhage (8 children), incidental lesions (2), and seizures (1); 2 children had choreiform movement disorders. Treatment was observation or surgery. Observation was chosen for 5 children either because the lesions were asymptomatic (2 children) or because the risk for neurological dysfunction after attempted excision was believed to be high (3 children). These 5 children were observed over a combined total of 30.4 patient-years; none experienced neurological deterioration or symptomatic hemorrhage from their lesions. The other 6 children underwent microsurgical resection of the lesion because they were symptomatic from hemorrhage or increasing mass effect. All 6 of these children had hemorrhagic lesions, of which the smallest dimension was at least 1.5 cm. Of these 6 lesions, 5 were excised completely, and over a combined total of 46 patient-years of follow-up, no rebleeding or late neurological deterioration after surgery was reported. Conclusions In this patient population, the natural history of small and asymptomatic CMs of the basal ganglia was benign. The children with large (> 1.5 cm) symptomatic lesions underwent excision; neurological impairment was apparently minimal, and no hemorrhage or neurological deterioration occurred later.
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Kumar, Anita J., Darcy Banco, Elise Steinberger, Shital Makim, and Susan Parsons. "3070 Time to Diagnostic Resolution After an Abnormal Screening Mammogram: a Single-Center Experience in an Underserved Hospital." Journal of Clinical and Translational Science 3, s1 (March 2019): 97. http://dx.doi.org/10.1017/cts.2019.221.
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OBJECTIVES/SPECIFIC AIMS: The study aims to identify patient and provider factors associated with delay in diagnostic resolution after an abnormal screening mammogram, with an emphasis on whether patients who spoke Chinese as their primary language sustained longer times to resolution. Primary outcome is to identify what proportion of patients achieve diagnostic resolution after abnormal screening mammogram within 90 days. Secondary outcome is to identify whether Chinese-speaking patients experience longer times to diagnostic resolution. METHODS/STUDY POPULATION: We performed a single-center retrospective cohort study at Tufts Medical Center (TMC), a tertiary care hospital that serves as the primary referral site for the Chinatown neighborhood in Boston. We included patients who underwent screening mammogram between 10/1/2015-9/30/2016 which was resulted as BIRADS-0 (non-diagnostic). Diagnostic resolution was defined as BIRADS-1, 2, or 3 imaging or definitive biopsy. We collected data on patient demographics (age, insurance plan, race/ethnicity, primary language, history of cancer), provider characteristics (referring provider location), and post-referral testing. Insurance was categorized as private-only or subsidized. Poverty was categorized using the American Fact Finder database, with a binary variable of <20% of ≥20% people in poverty for a given zip code. We performed descriptive statistics for all variables. We will perform multivariable Cox regression analyses to determine whether Chinese-speaking patients experience longer time to diagnostic resolution, adjusting for age, referring provider type, insurance status, poverty, and breast cancer history. We will use p<0.05 for our threshold for significance. RESULTS/ANTICIPATED RESULTS: We identified 386 patients who met inclusion criteria. Over half (55.9%) of patients were Caucasian, the mean age of study patients was 59 years, and 22% of patients were classified as poor. English was the most commonly spoken primary language (77.7%), while 15.3% of patients identified a Chinese dialect as their primary language. Most patients solely used private insurance for their medical care (73.1%). Majority of patients (83%) presented after undergoing a routine screening mammography, but a considerable proportion (14.4%) had prior breast cancer or a palpable mass. Most patients were referred for their screening mammogram by a hospital-based provider at TMC (85%), of which 77% of TMC referrals were from primary care. We also noted a limited number of referrals from community health centers, private practices and other PCP’s (Table 1). We will calculate median time to diagnostic resolution after screening mammogram and the proportion of patients who achieve resolution within 90 days. We will also calculate time to initiation of diagnostic workup, and whether this differed among Chinese-speaking patients, subsidized patients, or among those who were referred from outside of TMC. We will complete Cox multivariable analysis to identify if Chinese-speaking patients experience longer time to diagnostic resolution, adjusting for age, insurance status, Primary care provider location, poverty, and prior history of breast cancer. We will a priori test for an interaction between primary care provider within Tufts and Chinese as primary language to identify if a PCP within TMC modifies the relationship between Chinese language and time to resolution. DISCUSSION/SIGNIFICANCE OF IMPACT: The proposed study will identify whether disparities exist in time to achieving diagnostic resolution. Specifically, we will identify if patients who are primarily Chinese-speaking experience longer time to resolution. Our results will potentially provide the foundation for a patient navigation program to attenuate existing disparities by providing additional support for Chinese speaking patients in breast imaging workup.
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Hull, Leland E., David Cheng, Mie H. Hallman, M. L. Rieu-Werden, and Jennifer S. Haas. "Association of Patient and Site-of-Care Characteristics With Reproductive Carrier Screening Timing in a Large Integrated Health System." JAMA Network Open 5, no. 11 (November 8, 2022): e2240829. http://dx.doi.org/10.1001/jamanetworkopen.2022.40829.
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ImportanceReproductive genetic carrier screening can be performed prior to or during pregnancy to assess a reproductive couple’s risk of having a child with a recessively inherited disorder. Although professional societies endorse preconception screening as preferable to prenatal screening to allow for greater reproductive choice, implementation of preconception screening is challenging.ObjectiveTo determine how carrier screening timing varies by multilevel factors associated with health care delivery including patient, clinician, and location across a large integrated health care system.Design, Setting, and ParticipantsThis cross-sectional study used a mixed-methods approach including (1) quantitative analysis of multilevel factors associated with the timing of reproductive carrier screening and (2) qualitative analyses of data from interviews conducted with clinicians ordering carrier screenings. The setting was the Mass General Brigham, a large integrated health care system in the greater Boston, Massachusetts area. Participants included adult female patients who completed reproductive carrier screening performed by Myriad Women’s Health between October 1, 2018, to September 30, 2019.ExposuresSite of care (ordering clinical location and hospital affiliate), ordering clinician specialty, and patient characteristics, including age at date of test collection, self-reported race and ethnicity, primary insurance payor, and number of comorbidities.Main Outcomes and MeasuresThe primary outcome was the timing of carrier screening (preconception vs prenatal). A series of 4 multilevel logistic regression models were fitted to measure the relative contribution of site, clinician, and patient-level factors on the timing of screening. Interviews with ordering clinicians (N = 9) were analyzed using a framework approach to explore barriers to preconception screening.ResultsAmong 6509 adult female patients who completed carrier screenings, 770 (12%) were Asian, 352 (5%) were Hispanic, 640 (10%) were non-Hispanic Black, 3844 (59%) were non-Hispanic White, 858 (13%) were other or multiple races and ethnicities, and 2611 (40%) were aged 31 to 35 years; 4701 (63%) had prenatal screening and 2438 (37%) had preconception screening; screenings were ordered by 161 distinct clinicians across 32 clinical locations affiliated with 4 hospitals. In model 1, adjusted for hospital (fixed effect), clinic and clinician (random effects), 49% of the variability in timing was associated with clinician-level effects (intraclass correlation coefficient [ICC], 0.49) and 28% was associated with clinic-level effects (ICC, 0.28). Clinician specialty explained the greatest amount of variation in screening timing. Interviewed clinicians (N = 9) supported preconception screening but cited several barriers to offering population-based preconception screening.Conclusions and RelevanceIn this cross-sectional study, multilevel factors were associated with carrier screening timing. These findings suggest that increasing access to preconception screening may involve engaging specific medical specialties.
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Kildušis, Edvinas, and Gintautas Brimas. "The Impact of an Educational 3D Virtual Reality Video Method on Bowel Preparation for Colonoscopy: First Results." Lietuvos chirurgija 23, no. 2 (June 12, 2024): 108–15. http://dx.doi.org/10.15388/lietchirur.2024.23(2).4.
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Objective. Adequate bowel preparation is essential for diagnostic, screening, surveillance, and therapeutic colonoscopy. 3D virtual reality (3D-VR) has the characteristics of depth, interactivity and visuality and is widely used in medicine, so it can be used for patient education and training. The aim of our study is to determine the impact of using 3D virtual reality video for patients education on bowel preparation before colonoscopy. Materials and methods. A prospective, blind, randomized clinical trial was launched at the Republican Vilnius University Hospital (RVUL) on 07.03.2021, which included 50 outpatients who had indications for colonoscopy until 28.02.2022. Patients were randomly assigned to control and experimental groups. The first group was given the bowel preparation information in the standard form used by RVUL – in writing, and the second – in a 3D virtual reality video. The content of the information provided to both groups was the same. The quality of bowel preparation was assessed based on the Boston and Ottawa bowel preparation scales. Results. Of the 50 outpatients who participated in the study, 26 were assigned to the control group, 24 to the study group. The patients of both groups were identical in terms of sex, age, body mass index, comorbidities. The mean (SD) BBPS score was statistically significantly lower in the control group compared to the 3D-VR video group (5.96(±1) vs. 7.58(±1.47); p < 0.001). The mean (SD) scores of OBPS were higher in the control group (6.58(±2.44) than in the study group 1.83(±2.32); p < 0.001). The rate of adequate bowel preparation in the 3D-VR video group was higher than in the control group (18(69.23%) vs. 23(95.83%); the difference was statistically significant (p = 0.024)). The rate of terminal ileum intubation in the control group was 50% compared to 83.33% in the 3D-VR video group (p = 0.02).The mean (SD) colonoscopy time was statistically significantly shorter in the 3D-VR video group 23.04(±3.66) minutes and 16.5(±4.28) minutes, p = <0.001. Conclusions. Patients who were informed by 3D-VR method before colonoscopy had statistically significantly better bowel preparation, as well as reduced procedure time and possibly increased detection rates of polyps and adenomas.
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Wheeler, Alexindra, Harry PW Kozakewich, Kumar Shashi, and Whitney Eng. "Pulmonary Infantile Hemangioma: Clinical and Histopathological Review of Eight Cases." Blood 138, Supplement 1 (November 5, 2021): 4209. http://dx.doi.org/10.1182/blood-2021-153745.
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Abstract Introduction Infantile hemangioma (IH) is the most common benign vascular tumor of childhood. It typically appears as a single cutaneous mass in the head, neck, and trunk area. IH that does not arise in the skin most commonly presents in the liver. The lesion emerges shortly after birth, rapidly enlarges within the first six months of life, and then spontaneously involutes by 5-10 years of age. Risk factors associated with IH complications include lesional size, location, and growth characteristics. Pulmonary IH is rare with limited reports of clinical presentations and outcomes. Methods An IRB-approved, retrospective review of pediatric patients with a diagnosis of pulmonary IH was conducted. Cases were identified within the Department of Pathology at Boston Children's Hospital from surgical or autoptic specimens evaluated between 1918 and 2021. Analysis of histopathological slides confirmed pulmonary IH in eight infants. We describe the diagnostic workup, radiological, and histopathological findings of these eight patients. Results All patients presented with symptoms of respiratory distress, including tachypnea, subcostal retractions, and hypoxia. The median age at initial symptoms was 1.5 months (range, birth to 12 months). Five patients had a single pulmonary hemangioma ranging in size from 0.2 to 8.0 cm; three patients had multiple pulmonary hemangiomas. Four patients had co-occurrence of multifocal hepatic IH. The median age at histologic diagnosis of pulmonary IH was 6.5 months (range, 5 weeks to 16 months). Glucose transporter-1 (GLUT-1) immunostaining was positive in seven cases. Chest radiography demonstrated nonhomogeneous, mass-like consolidative opacities or rounded nodules. Treatment was primarily supportive. Three patients received medical therapy; two were treated with interferon, and one received propranolol. The infant treated with propranolol responded well with decreased lesional size and resolution of respiratory symptoms. Half of the patients in the cohort died; causes of death included cardiac failure from hepatic involvement, sepsis, hemorrhage, and liver failure. Conclusions Although IH is a common childhood tumor, IH of the lung is rare. Most (80%) IHs are focal, with hepatic co-involvement in 50-60% cases (Zavras et al. Eur J Pediatr, 2020; Hinen et al. Front Pediatr, 2020). Given that all patients who had concomitant hepatic hemangiomas died-albeit before the widespread availability of medical therapy-the presence of hepatic hemangiomas may confer high risk of complications. Patients with hepatic hemangiomas presented with pulmonary symptoms. Biopsy may be necessary to confirm the diagnosis of pulmonary IH and inform treatment. In this series, only treatment with propranolol or surgical resection was curative. Pulmonary IH should be considered in the differential diagnosis of infants with unexplained pulmonary masses, especially when accompanied by hepatic IH. Early recognition is critical for patients to receive proper and potentially life-saving treatment. Disclosures No relevant conflicts of interest to declare.
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Leiva, Orly, Umberto Campia, Julia Snyder, Briana Barns, Samantha Rizzo, Candrika Khairani, Hanny Al-Samkari, et al. "Increased Risk of Thrombosis in Patients with Myeloproliferative Neoplasms Compared with the General Population Hospitalized with COVID-19." Blood 138, Supplement 1 (November 5, 2021): 1508. http://dx.doi.org/10.1182/blood-2021-151801.
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Abstract Background: Coronavirus disease-2019 (COVID-19) is an inflammatory, multisystem infectious disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2) and is associated with increased risk of thrombosis, particularly among critically ill patients. The myeloproliferative neoplasms (MPNs) include Philadelphia chromosome-negative (Ph-negative) MPNs polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF), and Philadelphia-chromosome positive chronic myeloid leukemia (CML). Patients with MPNs, especially PH-negative, have increased risk of thrombotic complications. Given the increased propensity of thrombosis and prognostic significance of thrombosis in both COVID and MPNs, defining the risk of thrombotic complications in this patient population compared to the general population is important. Methods: Using an institutional database within the Mass General Brigham integrated health network, we retrospectively analyzed 63 consecutive patients with MPN who were ≥ 18 years old and tested positive for SARS-COV-2 infection based on polymerase chain reaction (PCR) testing from March 1, 2020 to January 1, 2021. We compared patients admitted to the hospital in our "MPN cohort" with patients admitted to the hospital from a separate COVID-19 (non-MPN cohort) Mass General Brigham registry of 1114 consecutive patients who tested positive for SARS-COV-2 infection based on PCR testing from March 13, 2020 to April 3, 2020. Care was taken to ensure the cohorts were mutually exclusive. The 90-day primary outcome for MPN cohort was a composite of all-cause death, any thrombosis (composite of arterial and venous thromboembolism [VTE]), International Society on Thrombosis and Haemostasis (ISTH) defined major and clinically relevant non-major bleeding. To identify risk factors for primary outcome in MPN cohort we used a multivariable logistic regression using age, sex, hospital admission status, MPN type, cytoreduction for MPN, hypertension, smoking status, baseline anticoagulation (AC), prior thrombosis (stroke, myocardial infarction or VTE) as co-variables. The 90-day outcomes of interest in our MPN vs non-MPN cohort analysis were any thrombosis, death, ISTH major and clinically relevant non-major bleeding and readmission for any reason. To assess impact of MPN status in hospitalized patients in our MPN vs non-MPN comparison, we used a multivariable logistic regression using age, sex, race, Hispanic ethnicity, ICU admission, treatment with steroids and/or Remdesivir, baseline AC and aspirin use, prior thrombosis (stroke, myocardial infarction or VTE), diabetes, heart failure, admission hematocrit, platelet count and D-dimer as co-variables. Continuous variables were compared using student t-test and categorical variables were compared using Fischer's Exact Test with a p value of < 0.05 considered significant. Results: Of the 63 patients with MPN (23 with PV, 17 ET, 4 PMF, 15 CML, 4 other), 27 (43%) were admitted to the hospital for COVID-19 and 5 (8%) required ICU admission. The mean age of all MPN patients was 66, 84% were White, 8% Black and 10% Hispanic. Primary 90-day outcome occurred in 12 (19%) of MPN patients. In multivariable analysis, only admission to hospital was associated with increased odds of composite (aOR 21.11, 95% CI 2.38 - 546.40), Figure 1A. In patients with (n = 27) and without MPN (n = 399) who were admitted to the hospital, patients with MPN were older (mean age 70 vs 61, p = 0.0076), more likely to be White (89% vs 54%, p = 0.0004) and less likely to be Hispanic (7% vs 29%, p = 0.0158), less likely to be admitted to the ICU (19% vs 43%, p = 0.0138), and more likely to be treated with corticosteroids (30% vs 14%, p = 0.025) or remdesivir (41% vs 13%, p < 0.0001). After multivariable logistic regression, diagnosis of MPN was significantly associated with increased odds of thrombosis (aOR 5.38, 95% CI 1.15-25.38) and readmission (aOR 6.28, 95% CI 1.60-24.88), but not bleeding (aOR 3.51, 95% CI 0.62-18.87) or death (aOR 4.29, 95% CI 0.95-18.99), Figure 1B. Conclusions: Thrombotic complications are common in patients with MPN and COVID-19, particularly if hospitalized for COVID-19. After multivariable analysis, MPN patients admitted for COVID-19 had a significantly increased risk of thrombotic complications compared with non-MPN patients. Figure 1 Figure 1. Disclosures Al-Samkari: Dova/Sobi: Consultancy, Research Funding; Novartis: Consultancy; Argenx: Consultancy; Rigel: Consultancy; Amgen: Research Funding; Agios: Consultancy, Research Funding; Moderna: Consultancy. Rosovsky: Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Inari: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees. Fathi: Agios/Servier: Consultancy, Other: Clinical Trial Support; BMS: Consultancy, Other: Clinical Trial Support; AbbVie: Consultancy, Other: Clinical Trial Support; Pfizer: Consultancy; Trillium: Consultancy; Kura: Consultancy; Blueprint Medicines Corporation: Consultancy; Genentech: Consultancy; Novartis: Consultancy; Trovagene: Consultancy; Daiichi Sankyo: Consultancy; Novartis: Consultancy; Morphosys: Consultancy; Kite: Consultancy; Foghorn: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Seattle Genetics: Consultancy; NewLink Genetics: Consultancy; Forty Seven: Consultancy; Ipsen: Consultancy. Goldhaber: Bayer: Consultancy, Research Funding; Boehringer-Ingelheim: Consultancy, Research Funding; BMS: Research Funding; Boston Scientific BTG EKOS: Research Funding; Daiichi: Research Funding; Janssen: Research Funding; Pfizer: Consultancy, Research Funding; Agile: Consultancy. Piazza: Portola: Research Funding; Bayer: Research Funding; Amgen: Research Funding; BMS: Research Funding; Janssen: Research Funding; BSC: Research Funding. Hobbs: Celgene/Bristol Myers Squibb: Consultancy; Novartis: Consultancy; Merck: Research Funding; Constellation Pharmaceuticals: Consultancy, Research Funding; Bayer: Research Funding; Incyte Corporation: Research Funding; AbbVie.: Consultancy.
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Simione, Meg, Holly M. Frost, Haley Farrar-Muir, Man Luo, Jazmin Granadeño, Carlos Torres, Alexy Arauz Boudreau, et al. "Evaluating the Implementation of the Connect for Health Pediatric Weight Management Program." JAMA Network Open 7, no. 1 (January 25, 2024): e2352648. http://dx.doi.org/10.1001/jamanetworkopen.2023.52648.
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ImportanceAdoption of primary care interventions to reduce childhood obesity is limited. Progress in reducing obesity prevalence and eliminating disparities can be achieved by implementing effective childhood obesity management interventions in primary care settings.ObjectiveTo examine the extent to which implementation strategies supported the uptake of research evidence and implementation of the Connect for Health pediatric weight management program.Design, Setting, and ParticipantsThis quality improvement study took place at 3 geographically and demographically diverse health care organizations with substantially high numbers of children living in low-income communities in Denver, Colorado; Boston, Massachusetts; and Greenville, South Carolina, from November 2019 to April 2022. Participants included pediatric primary care clinicians and staff and families with children aged 2 to 12 years with a body mass index (BMI) in the 85th percentile or higher.ExposuresPediatric weight management program with clinician-facing tools (ie, clinical decision support tools) and family-facing tools (ie, educational handouts, text messaging program, community resource guide) along with implementation strategies (ie, training and feedback, technical assistance, virtual learning community, aligning with hospital performance metrics) to support the uptake.Main Outcomes and MeasuresPrimary outcomes were constructs from the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) Framework examined through parent, clinician, and leadership surveys and electronic health record data to understand the number of children screened and identified, use of the clinical decision support tools, program acceptability, fidelity to the intervention and implementation strategies, and program sustainability.ResultsThe program screened and identified 18 333 children across 3 organizations (Denver Health, 8480 children [46.3%]; mean [SD] age, 7.97 [3.31] years; 3863 [45.5%] female; Massachusetts General Hospital (MGH), 6190 children [33.8%]; mean [SD] age, 7.49 [3.19] years; 2920 [47.2%] female; Prisma Health, 3663 children [20.0%]; mean [SD] age, 7.33 [3.15] years; 1692 [46.2%] female) as having an elevated BMI. The actionable flagging system was used for 8718 children (48%). The reach was equitable, with 7843 children (92.4%) from Denver Health, 4071 children (65.8%) from MGH, and 1720 children (47%) from Prisma Health being from racially and ethnically minoritized groups. The sites had high fidelity to the program and 6 implementation strategies, with 4 strategies (67%) used consistently at Denver Health, 6 (100%) at MGH, and 5 (83%) at Prisma Health. A high program acceptability was found across the 3 health care organizations; for example, the mean (SD) Acceptability of Intervention Measure score was 3.72 (0.84) at Denver Health, 3.82 (0.86) at MGH, and 4.28 (0.68) at Prisma Health. The implementation strategies were associated with 7091 (39%) uses of the clinical decision support tool. The mean (SD) program sustainability scores were 4.46 (1.61) at Denver Health, 5.63 (1.28) at MGH, and 5.54 (0.92) at Prisma Health.Conclusions and RelevanceThese findings suggest that by understanding what strategies enable the adoption of scalable and implementation-ready programs by other health care organizations, it is feasible to improve the screening, identification, and management of children with overweight or obesity and mitigate existing disparities.
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Melanson, Stacy. "Clinical Benefits of Direct-to-Definitive Testing for Monitoring Compliance in Pain Management." January 2018 1, no. 21;1 (November 14, 2018): E583—E592. http://dx.doi.org/10.36076/ppj.2018.6.e583.
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Background: The technical advantages of direct-to-definitive liquid chromatographytandem mass spectrometry (LC-MS/MS) urine testing for monitoring patient compliance in pain management are well known. However, the design and implementation of LC-MS/MS methods are more controversial, including factors such as determining appropriate cutoffs, specimen processing (e.g., specimen hydrolysis), reporting of qualitative and/or quantitative results, and test menu. Objectives: The objective of the research was to compare the clinical performance of our previous urine pain toxicology panel, a combination of immunoassay (IA) screens and LC-MS/MS, to our current pain toxicology panel, which features direct-to-definitive LC-MS/MS for 34 drugs and metabolites. Study Design: Six months of results from our previous pain toxicology panel were compared to 5.5 months of results from our current pain toxicology panel, enabling us to make conclusions regarding clinical performance. Setting: The research took place at Brigham and Women’s Hospital in Boston, MA. Methods: The percentage of false positive IA results was evaluated for our previous pain toxicology panel. The positivity rates for each drug and/or metabolite were calculated for both the previous and current panels, including rates of detection of both prescribed and illicit drugs. The turnaround time (TAT), direct and send-out costs associated with each approach, as well as projected cost savings were also determined. Results: False positive rates with IA ranged from 0% to 29%; the highest false positive rate was seen for 6-acetylmorphine (6-AM). The elimination of IA, addition of metabolites, and/or lowering of cutoffs increased the detection rate of 6-AM, benzoylecgonine (cocaine metabolite), fentanyl, morphine, and oxycodone. The ability to differentiate compliance from simulated compliance improved after eliminating specimen hydrolysis. The TAT improved significantly and projected yearly cost savings with the current panel was $95,003 (USD). In our opinion, qualitative results appeared sufficient to assess compliance in the majority of cases. Limitations: Our study was performed in a single academic center in a specific geographic region; therefore, our results may not be generalizable to other types of centers or regions. Conclusion: Direct-to-definitive LC-MS/MS testing has several clinical benefits, including reduction of false positive results, improved assessment of patient compliance, decreased TAT, and increased detection of drug use and abuse. Cost savings were also realized using this approach. Key words: Direct-to-definitive, LC-MS/MS, immunoassay, sensitivity, cost, pain management, turnaround time, patient compliance
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Webber, James W., Laura Wollborn, Sudhanshu Mishra, Allison Vitonis, Daniel W. Cramer, Ryan Phan, Todd Pappas, Dipanjan Chowdhury, and Kevin M. Elias. "Abstract A045: Improving the diagnostic accuracy of an ovarian cancer triage test using a joint miRNA-protein model." Cancer Research 84, no. 5_Supplement_2 (March 4, 2024): A045. http://dx.doi.org/10.1158/1538-7445.ovarian23-a045.
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Abstract Background: Multianalyte protein assays that combine several protein biomarkers with an individual’s menopausal status can aid in the preoperative prediction of ovarian cancer among women presenting with an adnexal mass. Serum microRNAs (miRNAs) are another class of biomarkers which have also shown potential to discriminate ovarian cancer cases from benign lesions or healthy controls. Here we investigate the complementarity of miRNA and protein-based approaches. Methods: The population consisted of serum samples from n=678 total study subjects. The training set was provided by Aspira Women’s Health, comprising n=568 women undergoing preoperative evaluation for an adnexal mass (n=333 benign and n=235 malignant). An independent, external validation set (n=110) comprised study subjects enrolled in prospective collection protocols at Brigham and Women’s Hospital, including n=59 subjects with benign masses or healthy controls and n=51 ovarian cancer cases. Among the 51 cases in the validation set, n=20 were FIGO Stage I/II and n=31 were FIGO Stage III/IV. Histologies included n=34 serous and n=17 non-serous. All samples underwent miRNA profiling using a custom 179-miRNA panel optimized for serum analysis using the Fireplex® circulating miRNA assay (Abcam, Cambridge, MA). Proteins were measured using ELISA kits by Aspira. Seven proteins were provided for each patient, including CA-125, as well as age and menopausal status. To reduce the dimensionality of the miRNA data, we employed a forward regression algorithm, which selects a subset of miRNA to optimize linear separation between cases and controls. The miRNA panel was combined with the protein and metadata to train a neural network to diagnose ovarian cancer. We used receiver operating characteristic curves to compare the effectiveness of models trained on miRNA + protein + metadata (joint) vs miRNA alone vs protein + metadata as assessed by the area under the curve (AUC). Results: The joint model produced an AUC 0.95 on the validation set. The miRNA and protein + metadata models offered an AUC of 0.84 and 0.9, respectively. By histology, the joint model offered the highest sensitivity among cancers which were serous and early-stage (89%) and among early-stage cancers overall (90%) when compared to miRNA alone (56% and 80%) or protein+metadata (67% and 65%). Conclusions: These results suggest that miRNA, protein, and metadata are complimentary tools, and the proposed model, which uses all data types simultaneously, is shown to offer the optimal AUC on the external validation set, when compared to the same model trained on miRNA alone or proteins and metadata. The joint model appears to be particularly effective for early-stage, high-risk histologies. This data will be useful to inform ovarian cancer screening and early detection efforts. Citation Format: James W. Webber, Laura Wollborn, Sudhanshu Mishra, Allison Vitonis, Daniel W. Cramer, Ryan Phan, Todd Pappas, Dipanjan Chowdhury, Kevin M. Elias. Improving the diagnostic accuracy of an ovarian cancer triage test using a joint miRNA-protein model [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A045.
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Zlotta, Alexandre R., Leslie K. Ballas, Andrzej Niemierko, Katherine Lajkosz, Cynthia Kuk, Gus Miranda, Michael Drumm, et al. "Multi-institutional matched comparison of radical cystectomy to trimodality therapy for muscle-invasive bladder cancer." Journal of Clinical Oncology 40, no. 6_suppl (February 20, 2022): 433. http://dx.doi.org/10.1200/jco.2022.40.6_suppl.433.
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433 Background: Prior randomized controlled trials (RCT) comparing bladder preservation to radical cystectomy (RC) for muscle invasive bladder cancer (MIBC) closed early due to lack of accrual. Given that no future RCTs are foreseen, and in the absence of level 1 data, we aimed to provide the best evidence possible on outcomes of matched cohorts comparing trimodality therapy (TMT, maximal transurethral resection of bladder tumor followed by concurrent chemoradiation) to RC in order to guide management. Methods: This retrospective analysis included 703 patients with MIBC clinical stage T2-T3/4aN0M0 MIBC urothelial carcinoma of the bladder, 421 RC and 282 TMT who would have been eligible for both TMT or RC, treated at the Massachusetts General Hospital, Boston; Princess Margaret Cancer Centre, Toronto; and University of Southern California, Los Angeles between 2005-2017. To compare homogeneous cohorts, all patients included in this analysis had solitary tumors < 7 cm, no or unilateral hydronephrosis, and no multifocal carcinoma in situ. Treatment propensity scores were estimated using logistic regression, and patients were matched 3:1 with replacement. Covariates included age, sex, clinical T stage, hydronephrosis, (neo)adjuvant chemotherapy, body mass index, smoking history, and ECOG status. Overall survival (OS) was estimated with adjusted Cox models; cancer-specific survival (CSS), distant failure-free survival, pelvic nodal failure-free survival and metastasis-free survival (combined distant and pelvic nodal failure) were estimated with adjusted competing risk models. Our primary endpoint of interest was metastasis-free survival. The analysis was performed as intent-to-treat. Results: The 3:1 matched cohort comprised of 1,116 patients (834 RC vs 282 TMT). After matching, age (71.3 vs 71.6), cT2 clinical stage (88 vs 90%), presence of hydronephrosis (12 vs 10%), and use of (neo)adjuvant chemotherapy (60 vs 65%) were similar between RC and TMT cohorts. Salvage cystectomy was performed in 38 patients (13%) treated by TMT. At 5 years, metastasis-free (73 vs 78%, p = 0.07), distant failure-free (78 vs 82%, p = 0.14), and pelvic nodal failure-free (96 vs 94%, p = 0.33) survival were not statistically different between RC and TMT, whereas CSS and OS favored TMT (78 vs 85%, p = 0.02; 70 vs 78%, p < 0.001). Outcomes for RC and TMT were not different among centers. Final pT stage in the RC patients was: pT0 14%, pT1 7%, pT2 29%, pT3/4 42% and N+ 24%. Peri RC mortality was 2.1% and median number of nodes removed was 40. NMIBC recurrence occurred in 57/278 (20.5%) TMT patients. Conclusions: This large multi-institutional contemporary study provides the best evidence to date, in the absence of randomized trials, supporting TMT for select patients with MIBC. Oncologic outcomes seem to be equivalent between TMT and RC, affirming the position that TMT should be offered as an effective alternative.
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Costello, Nancy, Rebecca Sutton, Madeline Jones, Mackenzie Almassian, Amanda Raffoul, Oluwadunni Ojumu, Meg Salvia, Monique Santoso, Jill R. Kavanaugh, and S. Bryn Austin. "ALGORITHMS, ADDICTION, AND ADOLESCENT MENTAL HEALTH: An Interdisciplinary Study to Inform State-level Policy Action to Protect Youth from the Dangers of Social Media." American Journal of Law & Medicine 49, no. 2-3 (July 2023): 135–72. http://dx.doi.org/10.1017/amj.2023.25.
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AbstractA recent Wall Street Journal investigation revealed that TikTok floods child and adolescent users with videos of rapid weight loss methods, including tips on how to consume less than 300 calories a day and promoting a “corpse bride diet,” showing emaciated girls with protruding bones. The investigation involved the creation of a dozen automated accounts registered as 13-year-olds and revealed that TikTok algorithms fed adolescents tens of thousands of weight-loss videos within just a few weeks of joining the platform. Emerging research indicates that these practices extend well beyond TikTok to other social media platforms that engage millions of U.S. youth on a daily basis.Social media algorithms that push extreme content to vulnerable youth are linked to an increase in mental health problems for adolescents, including poor body image, eating disorders, and suicidality. Policy measures must be taken to curb this harmful practice. The Strategic Training Initiative for the Prevention of Eating Disorders (STRIPED), a research program based at the Harvard T.H. Chan School of Public Health and Boston Children’s Hospital, has assembled a diverse team of scholars, including experts in public health, neuroscience, health economics, and law with specialization in First Amendment law, to study the harmful effects of social media algorithms, identify the economic incentives that drive social media companies to use them, and develop strategies that can be pursued to regulate social media platforms’ use of algorithms. For our study, we have examined a critical mass of public health and neuroscience research demonstrating mental health harms to youth. We have conducted a groundbreaking economic study showing nearly $11 billion in advertising revenue is generated annually by social media platforms through advertisements targeted at users 0 to 17 years old, thus incentivizing platforms to continue their harmful practices. We have also examined legal strategies to address the regulation of social media platforms by conducting reviews of federal and state legal precedent and consulting with stakeholders in business regulation, technology, and federal and state government.While nationally the issue is being scrutinized by Congress and the Federal Trade Commission, quicker and more effective legal strategies that would survive constitutional scrutiny may be implemented by states, such as the Age Appropriate Design Code Act recently adopted in California, which sets standards that online services likely to be accessed by children must follow. Another avenue for regulation may be through states mandating that social media platforms submit to algorithm risk audits conducted by independent third parties and publicly disclose the results. Furthermore, Section 230 of the federal Communications Decency Act, which has long shielded social media platforms from liability for wrongful acts, may be circumvented if it is proven that social media companies share advertising revenues with content providers posting illegal or harmful content.Our research team’s public health and economic findings combined with our legal analysis and resulting recommendations, provide innovative and viable policy actions that state lawmakers and attorneys general can take to protect youth from the harms of dangerous social media algorithms.
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Kadin, Marshall E., Helen Hu, Elena Elena Shklovskaya, Anand Deva, Mark Dooner, and Haiying Xu. "Abstract A08: Diagnosis of breast implant associated anaplastic large cell lymphoma by analysis of cytokines in peri-implant effusions." Blood Cancer Discovery 3, no. 5_Supplement (September 6, 2022): A08. http://dx.doi.org/10.1158/2643-3249.lymphoma22-a08.
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Abstract Introduction: Breast implant associated anaplastic large cell lymphoma (BIA-ALCL) was recently recognized by the WHO as a lymphoma presenting a median of 8 years after insertion of breast implants for reconstructive surgery following breast cancer, for prophylactic mastectomy due to high genetic risk of breast cancer, e.g. BRACA1/2 mutations, or for other cosmetic reasons. The American Society of Plastic Surgeons BIA-ALCL Global Network reports there are 1,158 known cases of BIA-ALCL and 35 deaths across 46 countries worldwide as of January 28, 2022. Approximately 80% of Australian women present with a peri-implant effusion whereas in the USA, 30% present with a mass +/- lymphadenopathy. Five-year overall survival is 90.1% when disease is confined to a peri-implant effusion and capsule but 72.4% when disease extends beyond the capsule. Therefore, we set out to develop a diagnostic test for early disease detection in peri-implant effusions. Experimental procedure: Our initial publications from the USA and Italy revealed higher mean concentrations of IL-9, IL-10 and IL-13 in BIA-ALCL than in more common benign effusions due to capsule contracture, leakage, trauma and infection. To validate these findings in a larger number of patients, mostly from another geographic region (Australia), we evaluated cryopreserved peri-implant effusions of 25 patients with BIA-ALCL and 30 patients with benign seromas collected at Macquarie University Medical School in Sydney AU and Rhode Island Hospital in the USA. Informed consent and Institutional approvals were obtained. Cytokine concentrations were determined with the Biolegend Human Th Cytokine 12 plex multianalyte flow assay kit (Cat. No. 741028), San Diego, USA. Results: The results show that mean levels of IL-9, IL-10 and IL-13 were elevated 72-, 716- and 22-fold, respectively, in BIA-ALCL compared to benign effusions, and each cytokine separated the two groups with little overlap (P < 0.0001), Mann-Whitney test. For IL-10, there was 92% sensitivity, 100% specificity, Youden Index (YIA08_92), cut-off value 150pg/ml; for IL-9, 96% sensitivity, 80% specificity (YI=76) cut-off value 88pg/ml; for IL-13, 76% sensitivity, 96.7% specificity, (YI= 72.7) cut-off value 714pg/ml. Furthermore, the geometric mean of the 3 cytokines has an area under the Receiver Operated Curve (AUROC) value of 0.9947 with 100% sensitivity and 96% specificity (Youden index of 96). Only one other cytokine, IFNgamma, showed significant diagnostic value.Conclusions: Measurement of a panel of 12 cytokines representing different T helper subsets discriminates with high sensitivity and specificity peri-implant effusions of BIA-ALCL from benign peri-implant effusions, facilitating early diagnosis with potential for curative surgery. The consistent cytokine profile of IL-9, IL-10 and IL-13 in malignant peri-implant effusions in this and 2 previous studies of 40 patients across 3 continents suggest that a specific immune response to unique etiologic agent(s) is an early event in the pathogenesis of BIA-ALCL. Citation Format: Marshall E Kadin, Helen Hu, Elena Elena Shklovskaya, Anand Deva, Mark Dooner, Haiying Xu. Diagnosis of breast implant associated anaplastic large cell lymphoma by analysis of cytokines in peri-implant effusions [abstract]. In: Proceedings of the Third AACR International Meeting: Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2022 Jun 23-26; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2022;3(5_Suppl):Abstract nr A08.
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Weinacht, Katja G. "Linking Oxidative Stress to Cell Fate-Ipsc-Based Disease Modeling Identifies New Therapeutic Target in Reticular Dysgenesis." Blood 124, no. 21 (December 6, 2014): 227. http://dx.doi.org/10.1182/blood.v124.21.227.227.
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Reticular Dysgenesis (RD) is one of the most serious forms of severe combined immune deficiency (SCID). It is characterized by complete absence of circulating lymphocytes and neutrophils. In addition, patients suffer from sensorineural hearing loss. Before newborn screening for SCID was implemented, the majority of patients succumbed to infection long before hematopoietic cell transplantation (HCT) could be attempted. To this date, the prognosis for RD remains grim. RD is caused by mutations in the mitochondrial ADP-generator Adenylate Kinase 2 (AK2). AK1 is a cytosolic protein that may compensate in various tissues for the lack of AK2. However, AK1 is not expressed in leukocytes and the stria vascularis of the inner ear [1]. While this observation may explain where AK2 defects manifest, the molecular mechanisms how AK2 defects take effect, remain largely obscure. Significant obstacles to elucidating disease pathology have been the lack of a suitable animal models and the unavailability of patient specimens. Using skin fibroblasts from an RD-patient we have recently identified at Boston Children’s Hospital [2], we have generated induced pluripotent stem cells (iPSC) with homozygous loss of function mutation in AK2. In-vitro myeloid differentiation of AK2-mutated iPSCs recapitulates the characteristic maturation arrest at the promyelocyte stage observed in-vivo in patients with this condition. AK2 is expressed in the intermitochondrial space and serves as primary mitochondrial ADP generator by promoting the reversible reaction AMP + ATP = 2 ADP. Maintenance of adequate levels of ADP is critical to support ATP synthase activity. Using Mass Spectrometry, we have shown that decreased AK2 activity leads to an increase in the AMP/ADP ratio in iPS-derived myeloid cells, indicating that AK2 is indispensable in maintaining ADP supply in the myeloid lineage. We have also performed transcriptome analysis of AK2- mutated myeloid cells compared to control and found a significant down regulation of ATP-dependant transporters. Based on this data, we hypothesized that in patients with RD, ADP-depletion in myeloid progenitors leads to stage 4 respiration, a well defined state in mitochondrial biology, in which the ATP-synthase lacks substrate and decreases its activity. This causes a reduction in proton flux from the intermitochondrial space back into the matrix, transient rise in membrane potential, and an escalation in the formation of reactive oxygen species (ROS). The cell responds by activating “inducible uncoupling”, the opening of alternative proton pores, which allows proton flux back into the matrix, bypassing the ATP-synthase and foregoing the use of energy stored in the proton gradient. While this represents a cellular rescue mechanism in response to acute oxidative stress, extended oxidative-stress-induced uncoupling eventually leads to a decline in proton gradient and membrane potential and ultimately in demise of the cell. To test this hypothesis, we have added Glutathione, the primary endogenous cellular antioxidant, to the culture conditions. We also tested G-CSF and all-trans-retinoic acid (ATRA), agents known to promote promyelocyte differentiation to mature neutrophils in other conditions. While G-CSF had no, and ATRA clearly deleterious effects on myeloid maturation in AK2-mutated cells, Glutathione led to a significant improvement in differentiation, allowing development of mature neutrophils in-vitro. Our results suggest that cell fate in RD is linked to oxidative stress and identify antioxidants as a possible therapeutic approach that may help reduce early mortality due to severe infections in patients with RD. Disclosures No relevant conflicts of interest to declare.
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Ruban, Aruchuna, Michael A. Glaysher, Alexander D. Miras, Anthony P. Goldstone, Christina G. Prechtl, Nicholas Johnson, Jia Li, et al. "A duodenal sleeve bypass device added to intensive medical therapy for obesity with type 2 diabetes: a RCT." Efficacy and Mechanism Evaluation 7, no. 6 (November 2020): 1–130. http://dx.doi.org/10.3310/eme07060.
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Background The EndoBarrier® (GI Dynamics Inc., Boston, MA, USA) is an endoluminal duodenal–jejunal bypass liner developed for the treatment of patients with obesity and type 2 diabetes mellitus. Meta-analyses of its effects on glycaemia and weight have called for larger randomised controlled trials with longer follow-up. Objectives The primary objective was to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level reduction of ≥ 20%. The secondary objectives were to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level of < 42 mmol/mol, blood pressure of < 135/85 mmHg, and the effectiveness on total body weight loss. Additional secondary outcomes were to investigate the cost-effectiveness and mechanism of action of the effect of a duodenal–jejunal bypass liner on brain reward system responses, insulin sensitivity, eating behaviour and metabonomics. Design A multicentre, open-label, randomised controlled trial. Setting Imperial College Healthcare NHS Trust and University Hospital Southampton NHS Foundation Trust. Participants Patients aged 18–65 years with a body mass index of 30–50 kg/m2 and with inadequately controlled type 2 diabetes mellitus who were on oral glucose-lowering medications. Interventions Participants were randomised equally to receive intensive medical therapy alongside a duodenal–jejunal bypass liner device (n = 85) or intensive medical therapy alone for 12 months (n = 85), and were followed up for a further 12 months. Results There was no significant difference between groups in the percentage of patients achieving the glycaemic primary or secondary outcomes [primary outcome at 12 months: duodenal–jejunal bypass liner group 54.5% vs. control group 55.2% (odds ratio 0.93, 95% confidence interval 0.44 to 1.98; p = 0.85); primary outcome at 24 months: duodenal–jejunal bypass liner group 39.7% vs. control group 36.5% (odds ratio 1.13, 95% confidence interval 0.52 to 2.47; p = 0.75)]. Significantly more patients in the duodenal–jejunal bypass liner group than in the control group lost > 15% of their total body weight (duodenal–jejunal bypass liner group 24.2% vs. control group 3.7%; odds ratio 8.33, 95% confidence interval 1.78 to 39.0; p = 0.007) and achieved blood pressure targets (duodenal–jejunal bypass liner group 68.2% vs. control group 44.4%; odds ratio 2.57, 95% confidence interval 1.21 to 5.48; p = 0.014). These differences were observed at 12 months but not at 24 months. There were more adverse events in the duodenal–jejunal bypass liner group, including one liver abscess. The increase in peripheral insulin sensitivity was superior in the duodenal–jejunal bypass liner group. Spectroscopic analyses of plasma, urine and faeces revealed several distinct metabolic perturbations in the duodenal–jejunal bypass liner group but not in the control group. Brain reward responses to food cues were not different between groups. The number of mean quality-adjusted life-years gained was similar in both groups and the additional costs of the duodenal–jejunal bypass liner may outweigh the value of the health benefits by £2560 per patient treated. Conclusions The results show that the endoluminal duodenal–jejunal bypass liner was not superior to intensive medical therapy for glycaemic control and was associated with more adverse events. The duodenal–jejunal bypass liner was associated with significant weight loss and improvement in cardiometabolic parameters at 12 months but not at 24 months. Economic evaluation showed that the bypass liner was not cost-effective for glycaemic control or for weight loss. Trial registration Current Controlled Trials ISRCTN30845205. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 6. See the NIHR Journals Library website for further project information. This study was executed with the support of GI Dynamics Inc. and with the kind support of Nutricia Advanced Medical Nutrition for providing oral nutritional supplements.
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Kosyakovsky, Leah B., Emily Somerset, Angela J. Rogers, Michael Sklar, Jared R. Mayers, Augustin Toma, Yishay Szekely, et al. "Machine learning approaches to the human metabolome in sepsis identify metabolic links with survival." Intensive Care Medicine Experimental 10, no. 1 (June 17, 2022). http://dx.doi.org/10.1186/s40635-022-00445-8.
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Abstract Background Metabolic predictors and potential mediators of survival in sepsis have been incompletely characterized. We examined whether machine learning (ML) tools applied to the human plasma metabolome could consistently identify and prioritize metabolites implicated in sepsis survivorship, and whether these methods improved upon conventional statistical approaches. Methods Plasma gas chromatography–liquid chromatography mass spectrometry quantified 411 metabolites measured ≤ 72 h of ICU admission in 60 patients with sepsis at a single center (Brigham and Women’s Hospital, Boston, USA). Seven ML approaches were trained to differentiate survivors from non-survivors. Model performance predicting 28 day mortality was assessed through internal cross-validation, and innate top-feature (metabolite) selection and rankings were compared across the 7 ML approaches and with conventional statistical methods (logistic regression). Metabolites were consensus ranked by a summary, ensemble ML ranking procedure weighing their contribution to mortality risk prediction across multiple ML models. Results Median (IQR) patient age was 58 (47, 62) years, 45% were women, and median (IQR) SOFA score was 9 (6, 12). Mortality at 28 days was 42%. The models’ specificity ranged from 0.619 to 0.821. Partial least squares regression-discriminant analysis and nearest shrunken centroids prioritized the greatest number of metabolites identified by at least one other method. Penalized logistic regression demonstrated top-feature results that were consistent with many ML methods. Across the plasma metabolome, the 13 metabolites with the strongest linkage to mortality defined through an ensemble ML importance score included lactate, bilirubin, kynurenine, glycochenodeoxycholate, phenylalanine, and others. Four of these top 13 metabolites (3-hydroxyisobutyrate, indoleacetate, fucose, and glycolithocholate sulfate) have not been previously associated with sepsis survival. Many of the prioritized metabolites are constituents of the tryptophan, pyruvate, phenylalanine, pentose phosphate, and bile acid pathways. Conclusions We identified metabolites linked with sepsis survival, some confirming prior observations, and others representing new associations. The application of ensemble ML feature-ranking tools to metabolomic data may represent a promising statistical platform to support biologic target discovery.