Brigham and Women's Hospital

Silicone is utilized widely in medical devices for its compatibility with tissues and bodily fluids, making it a versatile material for implants and wearables. To effectively bond silicone devices to biological tissues, a reliable adhesive is required to create a strong and long‐lasting interface. This study introduces BioAdheSil, a silicone‐based bioadhesive designed to provide robust adhesion on both sides of the interface, facilitating bonding between dissimilar substrates, namely silicone devices and tissues. The adhesive's design focuses on two key aspects: wet tissue adhesion capability and tissue‐infiltration‐based long‐term integration. BioAdheSil is formulated by mixing soft silicone oligomers with siloxane coupling agents and absorbents for bonding the hydrophobic silicone device to hydrophilic biological tissues. Incorporation of biodegradable absorbents eliminates surface water and controls porosity, while silane crosslinkers provide interfacial strength. Over time, BioAdheSil transitions from non‐permeable to permeable through enzyme degradation, creating a porous structure that facilitates cell migration and tissue integration, potentially enabling long‐lasting adhesion. Experimental results demonstrate that BioAdheSil outperforms commercial adhesives and elicits no adverse response in rats. BioAdheSil offers practical utility for adhering silicone devices to wet tissues, including long‐term implants and transcutaneous devices. In this study, we demonstrate its functionality through applications such as tracheal stents and LVAD (Left Ventricular Assist Device) lines. This article is protected by copyright. All rights reserved

Objectives National societies recommend against performing routine daily laboratory testing without a specific indication. Unnecessary testing can lead to patient harm, such as hospital-acquired anemia. The objective of this study was to reduce repeat complete blood counts (CBCs) after initial testing. Methods This was a quality improvement initiative implemented across 11 safety net hospitals in New York City. A best practice advisory (BPA) was implemented that asked the user to remove a CBC if the last 2 CBCs within 72 hours had normal white blood cell and platelet counts and unchanged hemoglobin levels. The outcome measure was the rate of CBCs per 1000 patient days preintervention (January 8, 2020, to December 22, 2020) to postintervention (December 23, 2020, to December 7, 2021). The process measure was the acceptance rate of the BPA, defined as the number of times the repeat CBC order was removed through the BPA divided by the total number of times the BPA triggered. Results Across 11 hospitals, repeat CBC testing decreased by 12.3% (73.05 to 64.04 per 1000 patient days, P < .001). Six of the 11 hospitals exhibited statistically significant decreases, ranging from a 10% to 48.9% decrease of repeat CBCs. The overall BPA action rate was 20.0% (24,029 of 119,944 repeat CBCs). Conclusions This low-effort, electronic health record–based intervention can effectively reduce unnecessary laboratory testing.

Cancer treatment has dramatically changed over the last decade with the development of immunotherapy. Therapies including immune cytokines, immune checkpoint inhibition, intratumoral therapies, and cellular therapies are already widely used in the oncology clinic. Active development continues in these areas and in the development of vaccines, bispecific therapies, and more refined cellular therapies. In this review, we will examine the role that immune therapy has in cancer treatment and explore areas of future development.

COVID-19 has led to marked increases in healthcare worker distress. Studies of these phenomena are often limited to a particular element of distress or a specific subset of healthcare workers. We administered the Moral Injury Symptom Scale for Healthcare Professionals, Copenhagen Burnout Inventory, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 via online survey to 17,000 employees of a large academic medical center between December 2021 and February 2022. A total of 1945 participants completed the survey. Across all roles, the prevalence of moral injury, burnout, depression, and anxiety were 40.9%, 35.3%–60.6%, 25.4%, and 24.8%, respectively. Furthermore, 8.1% had been bothered by thoughts that they would be better off dead or of hurting themselves for “several days” or more frequently. Healthcare workers across all roles and practice settings are experiencing unsustainable levels of distress, with 1 in 12 regularly experiencing thoughts of self-harm.

At the end of gestation, fetal skeleton rapidly accumulates calcium, and bone development continues in offspring postnatally. To accommodate, maternal skeletal physiology is modulated in a serotonin‐dependent manner. Selective serotonin reuptake inhibitors (SSRIs) are generally considered safe for treatment of major depressive disorder, postpartum depression, and other psychiatric illnesses during the peripartum period, but because serotonin affects bone remodeling, SSRIs are associated with decreased bone mass across all ages and sexes, and the impact of SSRIs during fetal and postnatal development has not been fully investigated. In the present study, our aim was to examine developmental fluoxetine exposure on offspring skeleton and to assess varying degrees of impact depending on dose and window of exposure in short‐term and long‐term contexts. We established that a low dose of lactational fluoxetine exposure caused a greater degree of insult to offspring bone than either a low dose during fetal and postpartum development or a high dose during lactation only in mice. We further discovered lasting impacts of developmental fluoxetine exposure, especially during lactation only, on adult bone and body composition. Herein, we provide evidence fluoxetine exposure during early development may have detrimental effects on the skeleton of offspring at weaning and into adulthood.

Background Prior research has demonstrated that low- and low-middle-income countries (LLMICs) bear a higher burden of critical illness and have a higherrate of mortality from critical illness than high-income countries (HICs). Thereis a pressing need for improved critical care delivery in LLMICs to reduce thisinequity. This systematic review aimed to characterise the range of critical careinterventions and services delivered within LLMIC health care systems as re -ported in the literature. Methods A search strategy using terms related to critical care in LLMICs was implemented in multiple databases. We included English language articles withhuman subjects describing at least one critical care intervention or service in anLLMIC setting published between 1 January 2008 and 1 January 2020. Results A total of 1620 studies met the inclusion criteria. Among the included studies, 45% of studies reported on pediatric patients, 43% on adults, 23% oninfants, 8.9% on geriatric patients and 4.2% on maternal patients. Most of thecare described (94%) was delivered in-hospital, with the remainder (6.2%) tak-ing place in out-of-hospital care settings. Overall, 49% of critical care describedwas delivered outside of a designated intensive care unit. Specialist physiciansdelivered critical care in 60% of the included studies. Additional critical care wasdelivered by general physicians (40%), as well as specialist physician trainees(22%), pharmacists (16%), advanced nursing or midlevel practitioners (8.9%),ambulance providers (3.3%) and respiratory therapists (3.1%). Conclusions This review represents a comprehensive synthesis of critical caredelivery in LLMIC settings. Approximately 50% of critical care interventionsand services were delivered outside of a designated intensive care unit. Specialist physicians were the most common health care professionals involved incare delivery in the included studies, however generalist physicians were com-monly reported to provide critical care interventions and services. This study additionally characterised the quality of the published evidence guiding criticalcare practice in LLMICs, demonstrating a paucity of interventional and cost-ef-fectiveness studies. Future research is needed to understand better how to opti-mise critical care interventions, services, care delivery and costs in these settings. Registration PROSPERO CRD42019146802.

Aims The aim of this study was to establish consensus statements on the diagnosis, nonoperative management, and indications, if any, for medial patellofemoral complex (MPFC) repair in patients with patellar instability, using the modified Delphi approach. Methods A total of 60 surgeons from 11 countries were invited to develop consensus statements based on their expertise in this area. They were assigned to one of seven working groups defined by subtopics of interest within patellar instability. Consensus was defined as achieving between 80% and 89% agreement, strong consensus was defined as between 90% and 99% agreement, and 100% agreement was considered to be unanimous. Results Of 27 questions and statements on patellar instability, three achieved unanimous consensus, 14 achieved strong consensus, five achieved consensus, and five did not achieve consensus. Conclusion The statements that reached unanimous consensus were that an assessment of physeal status is critical for paediatric patients with patellar instability. There was also unanimous consensus on early mobilization and resistance training following nonoperative management once there is no apprehension. The statements that did not achieve consensus were on the importance of immobilization of the knee, the use of orthobiologics in nonoperative management, the indications for MPFC repair, and whether a vastus medialis oblique advancement should be performed. Cite this article: Bone Joint J 2023;105-B(12):1259–1264.

Aims The aim of this study was to establish consensus statements on medial patellofemoral ligament (MPFL) reconstruction, anteromedialization tibial tubercle osteotomy, trochleoplasty, and rehabilitation and return to sporting activity in patients with patellar instability, using the modified Delphi process. Methods This was the second part of a study dealing with these aspects of management in these patients. As in part I, a total of 60 surgeons from 11 countries contributed to the development of consensus statements based on their expertise in this area. They were assigned to one of seven working groups defined by subtopics of interest. Consensus was defined as achieving between 80% and 89% agreement, strong consensus was defined as between 90% and 99% agreement, and 100% agreement was considered unanimous. Results Of 41 questions and statements on patellar instability, none achieved unanimous consensus, 19 achieved strong consensus, 15 achieved consensus, and seven did not achieve consensus. Conclusion Most statements reached some degree of consensus, without any achieving unanimous consensus. There was no consensus on the use of anchors in MPFL reconstruction, and the order of fixation of the graft (patella first versus femur first). There was also no consensus on the indications for trochleoplasty or its effect on the viability of the cartilage after elevation of the osteochondral flap. There was also no consensus on postoperative immobilization or weightbearing, or whether paediatric patients should avoid an early return to sport. Cite this article: Bone Joint J 2023;105-B(12):1265–1270.

Background: Cigarette smokers have elevated cardiovascular risk factors, which contributes significantly to mortality. Although social media is a potential avenue to deliver smoking interventions, its role in health promotion among smokers remains relatively unexplored. Objective: To examine the uptake and impact of health-related social media use in cigarette smokers. Methods: Using data from the 2017-2020 Health Information National Trends Survey, we evaluated differences in health-related social media use between smokers and nonsmokers. Multivariable logistic regression was performed to examine the association between social media use and positive health behaviors. Results: We included 1863 current smokers and 13,560 nonsmokers; Most participants were women (51.0%), White (64.6%), and 49.2% were aged ≥50 years. Smokers who used ≥1 social media site for health-related purposes in the past year were significantly more likely to meet the guideline recommendations for: (i) weekly physical activity (AOR 2.00, 95% CI 1.23-3.24), (ii) daily vegetable intake (AOR 2.48, 95% CI 1.10-5.59), and (iii) weekly strength training (AOR 1.80, 95% CI 1.10-2.94). However, the odds of reporting intentions to quit smoking (AOR 1.81, 95% CI 0.98-3.34) and attempts at smoking cessation (AOR 1.68, 95% CI 0.90-3.12) did not differ by health-related social media use. Conclusion: Smokers use social media for health-related purposes at comparable rates to nonsmokers. While our findings indicate that these platforms present a novel opportunity for health promotion among smokers, future research exploring the utility of social media in smoking cessation is crucial.

U.S. prisons were especially susceptible to COVID-19 infection and death; however, data limitations have precluded a national accounting of prison mortality (including but not limited to COVID-19 mortality) during the pandemic. Our analysis of mortality data collected from public records requests (supplemented with publicly available data) from 48 Departments of Corrections provides the most comprehensive understanding to date of in-custody mortality during 2020. We find that total mortality increased by 77% in 2020 relative to 2019, corresponding to 3.4 times the mortality increase in the general population, and that mortality in prisons increased across all age groups (49 and under, 50 to 64, and 65 and older). COVID-19 was the primary driver for increases in mortality due to natural causes; some states also experienced substantial increases due to unnatural causes. These findings provide critical information about the pandemic’s toll on some of the country’s most vulnerable individuals while underscoring the need for data transparency and standardized reporting in carceral settings.

OBJECTIVE The distributions and proportions of lean and fat tissues may help better assess the prognosis and outcomes of patients with spinal metastases. Specifically, in obese patients, sarcopenia may be easily overlooked as a poor prognostic indicator. The role of this body phenotype, sarcopenic obesity (SO), has not been adequately studied among patients undergoing surgical treatment for spinal metastases. To this end, here the authors investigated the role of SO as a potential prognostic factor in patients undergoing surgical treatment for spinal metastases. METHODS The authors identified patients who underwent surgical treatment for spinal metastases between 2010 and 2020. A validated deep learning approach evaluated sarcopenia and adiposity on routine preoperative CT images. Based on composition analyses, patients were classified with SO or nonsarcopenic obesity. After nearest-neighbor propensity matching that accounted for confounders, the authors compared the rates and odds of postoperative complications, length of stay, 30-day readmission, and all-cause mortality at 90 days and 1 year between the SO and nonsarcopenic obesity groups. RESULTS A total of 62 patients with obesity underwent surgical treatment for spinal metastases during the study period. Of these, 37 patients had nonsarcopenic obesity and 25 had SO. After propensity matching, 50 records were evaluated that were equally composed of patients with nonsarcopenic obesity and SO (25 patients each). Patients with SO were noted to have increased odds of nonhome discharge (OR 6.0, 95% CI 1.69–21.26), 30-day readmission (OR 3.27, 95% CI 1.01–10.62), and 90-day (OR 4.85, 95% CI 1.29–18.26) and 1-year (OR 3.78, 95% CI 1.17–12.19) mortality, as well as increased time to mortality after surgery (12.60 ± 19.84 months vs 37.16 ± 35.19 months, p = 0.002; standardized mean difference 0.86). No significant differences were noted in terms of length of stay or postoperative complications when comparing the two groups (p > 0.05). CONCLUSIONS The SO phenotype was associated with increased odds of nonhome discharge, readmission, and postoperative mortality. This study suggests that SO may be an important prognostic factor to consider when developing care plans for patients with spinal metastases.

Background: Tremor is one of the most common neurological symptoms. Its clinical and neurobiological complexity necessitates novel approaches for deep and granular phenotyping. Instrumented neurophysiological analyses have proven useful for clinical management, but are highly resource-intensive and lack broad accessibility. Simplified bedside scores, on the other hand, lack the granularity to capture subtle but relevant tremor features. Addressing this gap, we develop a deep learning framework for the quantitative assessment of limb tremor utilizing only standard clinical videos. Methods: We engineer a visual perceptive limb tremor analysis tool based on Mediapipe, a convolutional neural network architecture for marker-less hand tracking: VIPER-Tremor. We validate it against gold standard methods, including marker-based motion capture, wrist-worn accelerometery, and clinical scoring across two independent clinical cohorts encompassing a total of 66 patients diagnosed with essential tremor and recorded in different therapeutic states of deep brain stimulation. Results: Computer vision-derived tremor metrics exhibit high convergent clinical validity to scores (Spearman’s rho= 0.55 – 0.86, p≤ .01) as well as an accuracy of up to 2.60mm and ≤0.21Hz for tremor amplitude and frequency measurements, matching gold-standard equipment. VIPER-Tremor is capable of extracting advanced tremor features relevant for differential diagnosis and enables therapeutic outcome prediction, a dimension which conventional tremor scores were unable to provide. Conclusion: VIPER-Tremor is an accurate, unbiased and highly accessible solution for smartphone video-based tremor analysis and yields comparable results to gold standard recordings. VIPER-Tremor presents a significant advancement in tremor analysis, combining accuracy and accessibility, and promises to be a pivotal tool in the emerging field of precision neurology, enhancing diagnostic and therapeutic approaches.

OBJECTIVES Although opioids are frequently used to treat pain, and are an important risk for ICU delirium, the association between ICU pain itself and delirium remains unclear. We sought to evaluate the relationship between ICU pain and delirium. DESIGN Prospective cohort study. SETTING A 32-bed academic medical-surgical ICU. PATIENTS Critically ill adults ( n = 4,064) admitted greater than or equal to 24 hours without a condition hampering delirium assessment. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Daily mental status was classified as arousable without delirium, delirium, or unarousable. Pain was assessed six times daily in arousable patients using a 0–10 Numeric Rating Scale (NRS) or the Critical Care Pain Observation Tool (CPOT); daily peak pain score was categorized as no (NRS = 0/CPOT = 0), mild (NRS = 1–3/CPOT = 1–2), moderate (NRS = 4–6/CPOT = 3–4), or severe (NRS = 7–10/CPOT = 5–8) pain. To address missingness, a Multiple Imputation by Chained Equations approach that used available daily pain severity and 19 pain predictors was used to generate 25 complete datasets. Using a first-order Markov model with a multinomial logistic regression analysis, that controlled for 11 baseline/daily delirium risk factors and considered the competing risks of unarousability and ICU discharge/death, the association between peak daily pain and next-day delirium in each complete dataset was evaluated. RESULTS Among 14,013 ICU days (contributed by 4,064 adults), delirium occurred on 2,749 (19.6%). After pain severity imputation on 1,818 ICU days, mild, moderate, and severe pain were detected on 2,712 (34.1%), 1,682 (21.1%), and 894 (11.2%) of the no-delirium days, respectively, and 992 (36.1%), 513 (18.6%), and 27 (10.1%) of delirium days ( p = 0.01). The presence of any pain (mild, moderate, or severe) was not associated with a transition from awake without delirium to delirium (aOR 0.96; 95% CI, 0.76–1.21). This association was similar when days with only mild, moderate, or severe pain were considered. All results were stable after controlling for daily opioid dose. CONCLUSIONS After controlling for multiple delirium risk factors, including daily opioid use, pain may not be a risk factor for delirium in the ICU. Future prospective research is required.

Background Pancreatic ductal adenocarcinoma (PDAC) is a challenging target for immunotherapy because it has an immunosuppressive tumor microenvironment. Neoadjuvant chemoradiotherapy can increase tumor-infiltrating lymphocyte (TIL) density, which may predict overall survival (OS). We hypothesized that adding programmed cell death protein 1 (PD-1) blockade to chemoradiotherapy would be well tolerated and increase TILs among patients with localized PDAC. Methods Patients were randomized 2:1 to Arm A (receiving pembrolizumab plus chemoradiotherapy (capecitabine and external beam radiation)) or Arm B (receiving chemoradiotherapy alone) before anticipated pancreatectomy. Primary endpoints were (1) incidence and severity of adverse events during neoadjuvant therapy and (2) density of TILs in resected tumor specimens. TIL density was assessed using multiplexed immunofluorescence histologic examination. Results Thirty-seven patients were randomized to Arms A (n=24) and B (n=13). Grade ≥3 adverse events related to neoadjuvant treatment were experienced by 9 (38%) and 4 (31%) patients in Arms A and B, respectively, with one patient experiencing dose-limiting toxicity in Arm A. Seventeen (71%) and 7 (54%) patients in Arms A and B, respectively, underwent pancreatectomy. Median CD8 ⁺ T-cell densities in Arms A and B were 67.4 (IQR: 39.2–141.8) and 37.9 (IQR: 22.9–173.4) cells/mm ² , respectively. Arms showed no noticeable differences in density of CD8 ⁺ Ki67 ⁺ , CD4 ⁺ , or CD4 ⁺ FOXP3 ⁺ regulatory T cells; M1-like and M2-like macrophages; or granulocytes. Median OS durations were 27.8 (95% CI: 17.1 to NR) and 24.3 (95% CI: 12.6 to NR) months for Arms A and B, respectively. Conclusions Adding pembrolizumab to neoadjuvant chemoradiotherapy was safe. However, no convincing effect on CD8 ⁺ TILs was observed.

Congenital heart defects are the most common type of birth defect, affecting 1% of live births. The underlying cause of congenital heart disease is frequently unknown. However, advances in human genetics and genome technologies have helped expand congenital heart disease pathogenesis knowledge during the last few decades. When the cardiac defects are part of a genetic syndrome, they are associated with extracardiac conditions and require multidisciplinary care and surveillance. Some genetic syndromes can have subtle clinical findings and remain undiagnosed well into adulthood. Each syndrome is associated with specific congenital and acquired comorbidities and a particular clinical risk profile. A timely diagnosis is essential for risk stratification, surveillance of associated conditions and counselling, particularly during family planning. However, genetic testing and counselling indications can be challenging to identify in clinical practice. This document intends to provide an overview of the most clinically relevant syndromes to consider, focusing on the phenotype and genotype diagnosis, outcome data, clinical guidelines and implications for care.

Background We sought to describe patterns of delivery of adjuvant (aRT) and salvage RT (sRT) in patients who underwent RP after receiving neoadjuvant androgen receptor pathway inhibitor (ARPI) before radical prostatectomy (RP) for high‐risk localized prostate cancer (HRLPC). Methods Two hundred eighteen patients treated on phase 2 neoadjuvant trials between 2006 and 2018 at two academic centers were evaluated. aRT and sRT were defined as receipt of RT with a PSA of ≤0.1 or >0.1 ng/mL, respectively. Primary outcomes were biochemical recurrence (BCR), defined as time from aRT/sRT to a PSA rising to >0.1 ng/mL, and metastasis‐free survival (MFS) after RT. Results Twenty‐three (11%) and 55 (25%) patients received aRT and sRT respectively. Median PSA at start of aRT and sRT was 0.01 and 0.16 ng/mL, and median duration from RP to RT was 5 and 14 months, respectively. All aRT patients had NCCN high‐risk disease, 30% were pN1 and 43% had positive surgical margins; 52% had prostate bed RT. Fifty‐one percent of sRT patients had biopsy Gleason 9–10, 29% were pT2 and 9% had positive surgical margins; 63% had RT to the prostate bed/pelvis. At a median follow‐up of 5.3 and 3.0 years after aRT and sRT, 3‐year freedom from BCR was 55% and 47%, and 3‐year MFS was 56% and 53%, respectively. Conclusions aRT was infrequently used in patients who received neoadjuvant ARPI before RP for HRLPC. Outcomes of aRT and sRT were similar but generally poor. Studies evaluating intensified systemic therapy approaches with postoperative RT in this high‐risk population are needed.

Many of the Alzheimer’s disease (AD) risk genes are specifically expressed in microglia and astrocytes, but how and when the genetic risk localizing to these cell types contributes to AD pathophysiology remains unclear. Here, we derive cell-type-specific AD polygenic risk scores (ADPRS) from two extensively characterized datasets and uncover the impact of cell-type-specific genetic risk on AD endophenotypes. In an autopsy dataset spanning all stages of AD (n = 1457), the astrocytic ADPRS affected diffuse and neuritic plaques (amyloid-β), while microglial ADPRS affected neuritic plaques, microglial activation, neurofibrillary tangles (tau), and cognitive decline. In an independent neuroimaging dataset of cognitively unimpaired elderly (n = 2921), astrocytic ADPRS was associated with amyloid-β, and microglial ADPRS was associated with amyloid-β and tau, connecting cell-type-specific genetic risk with AD pathology even before symptom onset. Together, our study provides human genetic evidence implicating multiple glial cell types in AD pathophysiology, starting from the preclinical stage.