The Use and Impact of a Decision Support Tool for Appendicitis Treatment.

OBJECTIVE: Since introducing new and alternative treatment options may increase decisional conflict, we aimed to describe the use of the decision support tool (DST) and its impact on treatment preference and decisional conflict. BACKGROUND: For the treatment of appendicitis, antibiotics are an effective alternative to appendectomy, with both approaches associated with a different set of risks (eg, recurrence vs surgical complications) and benefits (eg, more rapid return to work vs decreased chance of readmission). Patients often have limited knowledge of these treatment options, and DSTs that include video-based educational materials and questions to elicit patient preferences about outcomes may be helpful. Concurrent with the Comparing Outcomes of Drugs and Appendectomy trials, our group developed a DST for appendicitis treatment ( www.appyornot.org ). METHODS: A retrospective cohort including people who self-reported current appendicitis and used the AppyOrNot DST between 2021 and 2023. Treatment preferences before and after the use of the DST, demographic information, and Ottawa Decisional Conflict Scale (DCS) were reported after completing the DST. RESULTS: A total of 8243 people from 66 countries and all 50 U.S. states accessed the DST. Before the DST, 14% had a strong preference for antibiotics and 31% for appendectomy, with 55% undecided. After using the DST, the proportion in the undecided category decreased to 49% ( P < 0.0001). Of those who completed the Ottawa Decisional Conflict Score (DCS; n = 356), 52% reported the lowest level of decisional conflict (<25) after using the DST; 43% had a DCS score of 25 to 50, 5.1% had a DCS score of >50 and 2.5% had and DCS score of >75. CONCLUSIONS: The publicly available DST appyornot.org reduced the proportion that was undecided about which treatment they favored and had a modest influence on those with strong treatment preferences. Decisional conflict was not common after use. The use of this DST is now a component of a nationwide implementation program aimed at improving the way surgeons share information about appendicitis treatment options. If its use can be successfully implemented, this may be a model for improving communication about treatment for patients experiencing emergency health conditions.

Verbal Descriptions of the Probability of Treatment Complications Lead to High Variability in Risk Perceptions: A Survey Study.

OBJECTIVE: To assess whether different methods for communicating the probability of treatment complications for operative and nonoperative appendicitis treatments result in differences in risk perception. BACKGROUND: Surgeons must communicate the probability of treatment complications to patients, and how risks are communicated may impact the accuracy and variability in patient risk perceptions and ultimately their decision making. METHODS: A series of online surveys of American adults communicated the probability of complications associated with surgical or antibiotic treatment of acute appendicitis. Probability was communicated with verbal descriptors (eg, "uncommon"), point estimates (eg, "3% risk"), or risk ranges (eg, "1% to 5%"). Respondents then estimated the probability of a complication for a "typical patient with appendicitis." The Fligner-Killeen test of homogeneity of variance was used to compare the variability in respondent risk estimates based on the method of probability communication. RESULTS: Among 296 respondents, variance in probability estimates was significantly higher when verbal descriptions were used compared to point estimates ( P < 0.001) or risk ranges ( P < 0.001). Identical verbal descriptors produced meaningfully different risk estimates depending on the complication being described. For example, "common" was perceived as a 45.6% for surgical site infection but 61.7% for antibiotic-associated diarrhea. CONCLUSION: Verbal probability descriptors are associated with widely varying and inaccurate perceptions about treatment risks. Surgeons should consider alternative ways to communicate probability during informed consent and shared decision-making discussions.

Development and Feasibility Testing of a Decision Aid for Acute Appendicitis.

INTRODUCTION: Patients with acute uncomplicated appendicitis will be increasingly asked to choose between surgery and antibiotic management. We developed a novel decision aid for patients in the emergency department (ED) with acute appendicitis who are facing this choice. We describe the development of the decision aid and an initial feasibility study of its implementation in a busy tertiary care ED. MATERIALS AND METHODS: We conducted a prepost survey analysis comparing patients before and after standardized implementation of the decision aid. Patients were surveyed about their experience making treatment decisions after discharge from the hospital. The primary outcome measure was the total score on the decisional conflict scale (; 0-100; lower scores better). RESULTS: The study included 24 participants (12 in the predecision aid period; 12 in the post period). Only 33% of participants in each group knew antibiotics were a treatment option prior to arriving at the ED. Prior to implementing the use of decision aid, only 75% of patients reported being told antibiotics were a treatment option, while this increased to 100% after implementation of the decision aid. The mean total decisional conflict scalescores were similar in the pre and post periods (mean difference = 0.13, 95% CI: -13 - 13, P > 0.9). CONCLUSIONS: This novel appendicitis decision aid was effectively integrated into clinical practice and helped toinform patients about multiple treatment options. These data support further large-scale testing of the decision aid as part of standardized pathways for the management of patients with acute appendicitis.

The Significance of Upfront Knowledge of N2 Disease in Non-small Cell Lung Cancer.

BACKGROUND: Previous literature suggests that patients with non-small cell lung cancer (NSCLC) and unsuspected N2 disease (cN0, pN2) represent a distinct subgroup associated with improved overall survival compared to patients with N2 disease identified prior to resection (cN2, pN2). METHODS: Retrospective analysis of the National Cancer Database of patients from 2004 to 2011 with cN0 and cN2 status found to be pathologic stage III-N2 NSCLC after surgical resection. Comparison of 5-year survival of patients with unsuspected N2 disease versus those with known N2 disease after surgical resection using Kaplan-Meier analysis was made. The independent effect of unsuspected N2 disease on mortality was analyzed using multivariate analysis. RESULTS: A total of 3271 patients with pathologic stage III-N2 NSCLC underwent curative intent surgical resection with or without adjuvant chemotherapy or chemotherapy and radiation. Unsuspected N2 disease was identified in 48% of patients. Patients with unsuspected N2 disease were more likely to have T1 tumors (37 vs. 32%, p < 0.001). Unsuspected N2 disease did not impact 5-year overall survival compared with known N2 when adjuvant therapy was utilized (40 vs. 37%, p = 0.167). Multivariate analysis identified older age, higher comorbidity score, and treatment with surgery alone as independent risk factors for mortality. The presence of unsuspected N2 disease was not significant in this model. CONCLUSIONS: The findings of this study suggest that unsuspected N2 disease is associated with equivalent 5-year survival compared to cN2 disease when adjuvant therapy is employed. These results support the use of adjuvant chemotherapy and radiation therapy when confronted with unsuspected N2 disease after surgical resection for stage IIIA-NSCLC.

Length of Stay From the Hospital Perspective: Practice of Early Discharge Is Not Associated With Increased Readmission Risk After Lung Cancer Surgery.

OBJECTIVE: To determine if hospitals that routinely discharge patients early after lobectomy have increased readmissions. BACKGROUND: Hospitals are increasingly motivated to reduce length of stay (LOS) after lung cancer surgery, yet it is unclear if a routine of early discharge is associated with increased readmissions. The relationship between hospital discharge practices and readmission rates is therefore of tremendous clinical and financial importance. METHODS: The National Cancer Database was queried for patients undergoing lobectomy for lung cancer from 2004 to 2013 at Commission on Cancer-accredited hospitals, which performed at least 25 lobectomies in a 2-year period. Facility discharge practices were characterized by a facility's median LOS relative to the median LOS for all patients in that same time period. RESULTS: In all, 59,734 patients met inclusion criteria; 2687 (4.5%) experienced an unplanned readmission. In a hierarchical logistic regression model, a routine of early discharge (defined as a facility's tendency to discharge patients faster than the population median in the same time period) was not associated with increased risk of readmission (odds ratio 1.12, 95% confidence interval 0.97-1.28, P = 0.12). In a risk-adjusted hospital readmission rate analysis, hospitals that discharged patients early did not experience more readmissions (P = 0.39). The lack of effect of early discharge practices on readmission rates was observed for both minimally invasive and thoracotomy approaches. CONCLUSIONS: It is possible for hospitals to develop early discharge practices without increasing readmissions. Further study is needed to identify the critical practice elements that have enabled hospitals to aggressively discharge patients without increasing readmission risk.

Mapping brain activity at scale with cluster computing.

Understanding brain function requires monitoring and interpreting the activity of large networks of neurons during behavior. Advances in recording technology are greatly increasing the size and complexity of neural data. Analyzing such data will pose a fundamental bottleneck for neuroscience. We present a library of analytical tools called Thunder built on the open-source Apache Spark platform for large-scale distributed computing. The library implements a variety of univariate and multivariate analyses with a modular, extendable structure well-suited to interactive exploration and analysis development. We demonstrate how these analyses find structure in large-scale neural data, including whole-brain light-sheet imaging data from fictively behaving larval zebrafish, and two-photon imaging data from behaving mouse. The analyses relate neuronal responses to sensory input and behavior, run in minutes or less and can be used on a private cluster or in the cloud. Our open-source framework thus holds promise for turning brain activity mapping efforts into biological insights.

Postneoadjuvant adjuvant chemotherapy in resected N1 non-small cell lung cancer with residual nodal disease.

BACKGROUND AND OBJECTIVES: Nodal positivity following neoadjuvant chemotherapy in locally advanced non-small cell lung cancer (NSCLC) is considered a poor prognostic sign, but little data are available on the efficacy of adjuvant chemotherapy in these cases. This analysis sought to determine whether adjuvant chemotherapy was associated with increased survival in NSCLC patients with residual N1 disease at resection. METHODS: Patients from the National Cancer Database (NCDB) with cN1T1-2M0 NSCLC treated with neoadjuvant chemotherapy and definitive resection between 2006 and 2012 were identified. Treatment groups were defined as those receiving no additional therapy or adjuvant chemotherapy ± radiation after resection. Five-year overall survival (OS) was estimated for each group. Cox proportional hazard regression was used to estimate hazard ratios adjusting for demographic, clinical, and facility characteristics. RESULTS: Among 90 eligible patients, 5-year OS was 43% and 56% for patients receiving adjuvant chemotherapy and no additional treatment, respectively (P < 0.56). With multivariable analysis, the estimated hazard ratio was 0.61 (95% CI: 0.61-2.64, P = 0.51) for adjuvant chemotherapy compared to no additional therapy. CONCLUSION: This analysis suggests that adjuvant chemotherapy is not associated with increased survival in NSCLC patients with pathologic N1 NSCLC following neoadjuvant chemotherapy and resection.

Recognition of elevated blood pressure in an outpatient pediatric tertiary care setting.

OBJECTIVE: To assess the prevalence of elevated blood pressure (BP) and its identification among outpatients at a pediatric tertiary care hospital and to assess clinician attitudes towards BP management. STUDY DESIGN: A retrospective review was undertaken of electronic medical record data of visits over the course of 1 year to 10 subspecialty divisions and 3 primary care services at an urban tertiary care hospital. Interviews of division/service representatives and a clinician survey on perceived role on BP care, practices, and protocols related to BP management were conducted. Elevated BP was defined as ≥90th percentile (using US references); identification of elevated BP was defined as the presence of appropriate codes in the problem list or visit diagnoses. RESULTS: Among 29,000 patients (ages 2-17 years), 70% (those with ≥1 BP measurement) were analyzed. Patients were as follows: 50% male; 42% white, 31% Hispanic, 16% black, 5% Asian, and 5% other/missing; 52% had Medicaid insurance. A total of 64% had normal BPs, 33% had 1-2 elevated BP measurements, and 3% had ≥3 elevated BP measurements. Among those with ≥3 elevated BP measurements, the median frequency of identification by division/service was 17%; the greatest identification was for Kidney Diseases (67%), Wellness & Weight Management (60%), and Cardiology (33%). Among patients with ≥3 elevated BP measurements, 21% were identified vs 7% identified among those with 1-2 increased measurements (P<.001). All clinician survey respondents perceived self-responsibility for identification of elevated BP, but opinions varied for their role in the management of elevated BP. CONCLUSIONS: The identification of patients with elevated BP measurements was low. Strategies to increase the identification of elevated BPs in outpatient tertiary care settings are needed.

Mutations in GATA2 cause human NK cell deficiency with specific loss of the CD56(bright) subset.

Mutations in the transcription factor GATA2 underlie the syndrome of monocytopenia and B- and natural killer (NK)-cell lymphopenia associated with opportunistic infections and cancers. In addition, patients have recurrent and severe viral infections. NK cells play a critical role in mediating antiviral immunity. Human NK cells are thought to mature in a linear fashion, with the CD56(bright) stage preceding terminal maturation to the CD56(dim) stage, considered the most enabled for cytotoxicity. Here we report an NK cell functional defect in GATA2-deficient patients and extend this genetic lesion to what is considered to be the original NK cell-deficient patient. In most cases, GATA2 deficiency is accompanied by a severe reduction in peripheral blood NK cells and marked functional impairment. The NK cells detected in peripheral blood of some GATA2-deficient patients are exclusively of the CD56(dim) subset, which is recapitulated on in vitro NK cell differentiation. In vivo, interferon α treatment increased NK cell number and partially restored function but did not correct the paucity of CD56(bright) cells. Thus, GATA2 is required for the maturation of human NK cells and the maintenance of the CD56(bright) pool in the periphery. Defects in GATA2 are a novel cause of profound NK cell dysfunction.

Vitamin D levels, insulin resistance, and cardiovascular risks in very young obese children.

OBJECTIVE: To examine the relationships of 25-hydroxyvitamin D (25-OHD) levels with the measures of insulin resistance and cardiovascular risk, and identify the clinical factors associated with low 25-OHD in young obese children. DESIGN AND METHODS: Data from 83 children ages 2-6 years seen for obesity care (clinic latitude 42°N) were analyzed. Insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] and cardiovascular risks were examined in relationship to 25-OHD levels using correlation statistics. χ2 and logistic regression models were applied to identify the factors associated with vitamin D deficiency (25-OHD levels <20 ng/mL) and insufficiency (<30 ng/mL). RESULTS: Children's mean age was mean 4.9 years and they were predominantly Hispanic. Mean body mass index (BMI) Z-score was 3.2 and mean HOMA-IR was 2.8. Mean 25-OHD was 30.9 ng/mL (6% <20 ng/mL and 46% 20-29 ng/mL). There were no significant correlations between 25-OHD and BMI (Spearman's ρ=-0.096, p=0.389), BMI Z-score (Spearman's ρ=0.104, p=0.350), HOMA-IR (Spearman's ρ=-0.144, p=0.269), total cholesterol (Spearman's ρ=-0.028, p=0.833), or triglycerides (Spearman's ρ=-0.026, p=0.846). Vitamin D deficiency was significantly associated with older age, lower milk intake, and testing in winter months. 25-OHD level <30 ng/mL was associated with older age, African-American and Hispanic race/ethnicity, and testing in winter months. All factors retained significance in a multivariate logistic regression model, with African-American (odds ratio=14.4) and Hispanic (odds ratio=7.2) race/ethnicity being the strongest predictors of 25-OHD levels <30 ng/mL. CONCLUSIONS: In these children, 25-OHD was not associated with insulin resistance or cardiovascular risks. Considering age, race/ethnicity, diet, and season may help identify young obese children needing vitamin D management.

Direct GDP-KRASG12C inhibitors and mechanisms of resistance: the tip of the iceberg.

Kirsten rat sarcoma viral oncogene homolog mutations are observed in 25% of lung adenocarcinoma and 40% of these are G12C mutations. Historically, no approved targeted agents were available for patients with any KRAS mutation, and response rates to standard-of-care therapies were suboptimal. Newly developed inhibitors directed toward KRASG12C have been successful in clinical trials with overall response rates ranging between 32% and 46%, and two FDA approvals were granted in May 2021 and December 2022 as second-line or later monotherapies. However, rapid tumor resistance complicates their use as a monotherapy. With the rapid development of this novel class of inhibitors, it is important to discern the different types of tumor resistance that may arise and how each can differently contribute to tumor growth and survival. G12C inhibitor resistance is under investigation and combinations of therapies with G12C inhibitors have been proposed. Much of this insight is gleaned from preclinical investigations, as our knowledge of clinical resistance is in its infancy. In this review, we summarize the preclinical development of KRASG12C inhibitors, their clinical evaluations, different types of resistance mechanisms to these compounds, and ways of overcoming them. Finally, we underscore the importance of basic and translational investigations of these molecules in a landscape where their clinical evaluations garner the most attention, and we set the stage for what is to come.

Association between Risk Communication Format and Perceived Risk of Adverse Events after COVID-19 Vaccination among US Adults.

The format used to communicate probability-verbal versus numerical descriptors-can impact risk perceptions and behaviors. This issue is salient for the Coronavirus disease 2019 (COVID-19), where concerns about vaccine-related risks may reduce uptake and verbal descriptors have been widely used by public health, news organizations and on social media, to convey risk. Because the effect of risk-communication format on perceived COVID-19 vaccine-related risks remains unknown, we conducted an online randomized survey among 939 US adults. Participants were given risk information, using verbal or numerical descriptors and were asked to report their perceived risk of experiencing headache, fever, fatigue or myocarditis from COVID-19 vaccine. Associations between risk communication format and perceived risk were assessed using multivariable regression. Compared to numerical estimates, verbal descriptors were associated with higher perceived risk of headache (ß = 5.0 percentage points, 95% CI = 2.0-8.1), fever (ß = 27 percentage points, 95% CI = 23-30), fatigue (ß = 4.9 percentage points, 95% = CI 1.8-8.0) and myocarditis (ß = 4.6 percentage points, 95% CI = 2.1-7.2), as well as greater variability in risk perceptions. Social media influence was associated with differences in risk perceptions for myocarditis, but not side effects. Verbal descriptors may lead to greater, more inaccurate and variable vaccine-related risk perceptions compared to numerical descriptors.

BioDrugScreen: a computational drug design resource for ranking molecules docked to the human proteome.

BioDrugScreen is a resource for ranking molecules docked against a large number of targets in the human proteome. Nearly 1600 molecules from the freely available NCI diversity set were docked onto 1926 cavities identified on 1589 human targets resulting in >3 million receptor-ligand complexes requiring >200,000 cpu-hours on the TeraGrid. The targets in BioDrugScreen originated from Human Cancer Protein Interaction Network, which we have updated, as well as the Human Druggable Proteome, which we have created for the purpose of this effort. This makes the BioDrugScreen resource highly valuable in drug discovery. The receptor-ligand complexes within the database can be ranked using standard and well-established scoring functions like AutoDock, DockScore, ChemScore, X-Score, GoldScore, DFIRE and PMF. In addition, we have scored the complexes with more intensive GBSA and PBSA approaches requiring an additional 120,000 cpu-hours on the TeraGrid. We constructed a simple interface to enable users to view top-ranking molecules and access purchasing and other information for further experimental exploration.

Iron oxide nanoparticles for targeted cancer imaging and diagnostics.

Superparamagnetic iron oxide nanoparticles (SPIONs) have proven to be highly effective contrast agents for the magnetic resonance imaging diagnosis of solid tumors. This review examines the various techniques that are available to selectively target SPIONs toward a wide variety of cancerous tissues, with specific attention given to how the surface properties imparted by various targeting ligands affect the particles tissue distribution and pharmacokinetics. An in-depth examination of the various human cell lines utilized to test the assorted targeting methods is also presented, as well as an overview of the various types of cancer against which each targeting method has been utilized for both in vivo and in vitro studies. From the Clinical Editor: Functionalized superparamagnetic iron oxide nanoparticles (SPIONs) are very potent negative contrast materials for magnetic resonance imaging-based diagnosis. This comprehensive review examines techniques that selectively target SPIONs toward a wide variety of malignancies.

Respiratory events after intensive care unit discharge in trauma patients: Epidemiology, outcomes, and risk factors.

BACKGROUND: Respiratory complications are associated with significant morbidity and mortality in trauma patients. The care transition from the intensive care unit (ICU) to the acute care ward is a vulnerable time for injured patients. There is a lack of knowledge about the epidemiology of respiratory events and their outcomes during this transition. METHODS: Retrospective cohort study in a single Level I trauma center of injured patients 18 years and older initially admitted to the ICU from 2015 to 2019 who survived initial transfer to the acute care ward. The primary outcome was occurrence of a respiratory event, defined as escalation in oxygen therapy beyond nasal cannula or facemask for three or more consecutive hours. Secondary outcomes included unplanned intubation for a primary pulmonary cause, adjudicated via manual chart review, as well as in-hospital mortality and length of stay. Multivariable logistic regression was used to examine patient characteristics associated with posttransfer respiratory events. RESULTS: There were 6,561 patients that met the inclusion criteria with a mean age of 52.3 years and median Injury Severity Score of 18 (interquartile range, 13-26). Two hundred and sixty-two patients (4.0%) experienced a respiratory event. Respiratory events occurred early after transfer (median, 2 days, interquartile range, 1-5 days), and were associated with high mortality (16% vs. 1.8%, p < 0.001), and ICU readmission rates (52.6% vs. 4.7%, p < 0.001). Increasing age, male sex, severe chest injury, and comorbidities, including preexisting alcohol use disorder, congestive heart failure, and chronic obstructive pulmonary disease, were associated with increased odds of a respiratory event. Fifty-eight patients experienced an unplanned intubation for a primary pulmonary cause, which was associated with an in-hospital mortality of 39.7%. CONCLUSION: Respiratory events after transfer to the acute care ward occur close to the time of transfer and are associated with high mortality. Interventions targeted at this critical time are warranted to improve patient outcomes. LEVEL OF EVIDENCE: Prognostic and Epidemiological study, level III.

Randomized Pilot Test of a Decision Support Tool for Acute Appendicitis: Decisional Conflict and Acceptability in a Healthy Population.

To test the effect of a new decision support tool for acute appendicitis and assess its efficacy and acceptability. Background: Mounting evidence from randomized controlled trials have shown that antibiotics can be a safe and effective treatment for appendicitis. Patients and surgeons must work together to choose the optimal treatment approach for each patient based on their own preferences and values. We developed a decision support tool to facilitate shared decision-making for appendicitis and its effect on decisional outcomes remains unknown. Methods: We conducted an online randomized field test in at-risk individuals comparing the decision support tool to a standard infographic. Individuals were randomized 3:1 to view the decision support tool or infographic. The primary outcome was the total decisional conflict scale (DCS) score measured before and after exposure to the decision support tool. Secondary outcomes included between-group DCS scores, and between-group comparisons of the acceptability. Results: One hundred eighty individuals were included in the study. Total DCS scores decreased significantly after viewing the decision support tool (59 [95% confidence interval (CI): 55-63] to 15 [95% CI: 12-17], P < 0.001) representing movement from a state of high to low decisional conflict. Individuals exposed to the decision support tool reported higher acceptability ratings (3.7 [95% CI: 3.6-3.8] vs 3.3 [95% CI: 3.2-3.5] out of 4) and demonstrated increased willingness to consider both treatment options. Conclusions: These data support the further use and testing of this novel decision support tool in patients with acute appendicitis.

Association Between Statewide Medicaid Opioid Policy and Postoperative Opioid Prescribing among Surgeons at a Large Safety-Net Hospital.

BACKGROUND: Restrictive state and payer policies may be effective in reducing opioid prescribing by surgeons, but their impact has not been well studied. In 2017, Washington Medicaid implemented an opiod prescribing limit of 42 pills, prompting a large regional safety-net hospital to implement a decision support intervention in response. We aimed to evaluate the effects on surgeons' prescribing. STUDY DESIGN: We retrospectively studied postoperative opioid prescribing (quantity of pills prescribed at discharge) to opioid-naïve surgical patients at a regional safety-net hospital from 2016 to 2020. We investigated associations between the policy and opioid prescribing by using interrupted time series analysis, adjusting for clinical and sociodemographic factors. RESULTS: A total of 12,799 surgical encounters involving opioid-naïve patients (59% male, mean age 52) were analyzed. Opioids were prescribed for 75%. From 2016 to 2020, the mean prescribed opioid quantity decreased from 36 pills to 17 pills. In interrupted time series analysis, the Medicaid policy implementation was associated with an immediate change of -8.4 pills (95% CI -12 to -4.7; p < 0.001) per prescription and a subsequent rate of decrease similar to that prepolicy. In a comparison of changes between patients insured through Medicaid vs Medicare, Medicaid patients had an immediate change of -9.8 pills (95% CI -19 to -0.76; p = 0.03) after policy implementation and continued decreases similar to those prepolicy. No immediate or subsequent policy-related changes were observed among Medicare patients. CONCLUSION: In a large regional safety-net institution, postoperative opioid prescriptions decreased in size over time, with immediate changes associated with a state Medicaid policy and corresponding decision support intervention. These findings pose implications for surgeons, hospital leaders, and payers seeking to address opioid use via judicious prescribing.

Surface functionalization of silica nanoparticles with cysteine: a low-fouling zwitterionic surface.

Herein, we report on the functionalization of silica nanoparticles with a small molecule, the amino acid cysteine, in order to create a low-fouling zwitterionic surface for nanomedicine applications. The cysteine functionalization was shown to impart the particles with excellent stability in both salt and single-protein solutions of lysozyme (positively charged) and bovine serum albumin (negatively charged). Bare silica particles precipitated immediately in a lysozyme solution, while cysteine-functionalized particles were stable for 20 h. Furthermore, the particles displayed excellent long-term stability in solutions of human serum showing no aggregation over a period of 14 days. The functionalized particles also possess multiple reactive surface groups for further coupling reactions. We believe that the surface functionalization schemes described in this report represent a versatile and effective method of stabilizing nanoparticle systems in biological media for their use in a variety of therapeutic and diagnostic applications.