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Pancreaticoduodenectomy is a highly morbid operation with significant resource utilization. Using a national cohort, we examined the interhospital variation in pancreaticoduodenectomy hospitalization cost in the United States. Adults undergoing elective pancreaticoduodenectomy in the setting of pancreatic cancer were tabulated from the 2016–2020 Nationwide Readmissions Database. A 2-level mixed-effects model was developed to evaluate the interhospital variation in pancreaticoduodenectomy hospitalization costs. Institutions within the top decile of risk-adjusted expenditures were defined as high-cost hospitals. Multivariable regression models were fitted to examine the association between high-cost hospital status and outcomes of interest. To account for the effects of complications on expenditures, a subgroup analysis comprising of patients with no adverse events was conducted. The study included an estimated 24,779 patients with a median hospitalization cost of $38,800. After mixed-effects modeling, 40.9% of the cost variation was attributable to hospital, rather than patient, factors. Multivariable regression models revealed an association between high-cost hospital status and greater odds of complications and longer length of stay. Among patients without an adverse event, interhospital cost variation remained significant at 61.0%, and treatment at high-cost hospitals was similarly linked to longer length of stay. Our study identified significant interhospital variation in pancreaticoduodenectomy hospitalization costs in the United States. Although high-cost hospital status was associated with increased odds of complications, variation remained significant even among patients without an adverse event. These results suggest the important role of hospital practices as contributors to expenditures. Further efforts to identify drivers of costs and standardize pancreatic surgical care are warranted. [ABSTRACT FROM AUTHOR]

Multi-arterial coronary bypass grafting with the left internal mammary artery as a conduit has been shown to offer superior long-term survival compared to single-arterial coronary bypass grafting. Nevertheless, the selection of a secondary conduit between the right internal mammary artery and the radial artery remains controversial. Using a national cohort, we examined the relationships between the right internal mammary artery and the radial artery with acute clinical and financial outcomes. Adults undergoing on-pump multivessel coronary bypass grafting with left internal mammary artery as the first arterial conduit were identified in the 2016 to 2020 Nationwide Readmissions Database. Patients receiving either the right internal mammary artery or the radial artery, but not both, were included in the analysis. Multivariable regression models were fitted to examine the association between the conduits and in-hospital mortality, as well as additional secondary outcomes. Of an estimated 49,798 patients undergoing multi-arterial coronary bypass grafting, 29,729 (59.7%) comprised the radial artery cohort. During the study period, the proportion of multi-arterial coronary bypass grafting utilizing the radial artery increased from 51.3% to 65.2% (nptrend <0.001). Following adjustment, the radial artery was associated with reduced odds of in-hospital mortality (adjusted odds ratio 0.44), prolonged mechanical ventilation (adjusted odds ratio 0.78), infectious complications (adjusted odds ratio 0.69), and 30-day nonelective readmission (adjusted odds ratio 0.77, all P <.05). Despite no definite endorsement from surgical societies, the radial artery is increasingly utilized as a secondary conduit in multi-arterial coronary bypass grafting. Compared to the right internal mammary artery, the radial artery was associated with lower odds of in-hospital mortality, complications, and reduced healthcare expenditures. These results suggest that whenever feasible, the radial artery should be the favored conduit over the right internal mammary artery. Nevertheless, future studies examining long-term outcomes associated with these vessels remain necessary. [ABSTRACT FROM AUTHOR]

Acute complicated diverticulitis poses a substantial burden to individual patients and the health care system. A significant proportion of the cases necessitate emergency operations. The choice between Hartmann's procedure and primary anastomosis with diverting loop ileostomy remains controversial. Using American College of Surgeons National Surgical Quality Improvement Program patient user file data from 2012 to 2020, patients undergoing Hartmann's procedure and primary anastomosis with diverting loop ileostomy for nonelective sigmoidectomy for complicated diverticulitis were identified. Major adverse events, 30-day mortality, perioperative complications, operative duration, reoperation, and 30-day readmissions were assessed. Of 16,921 cases, 6.3% underwent primary anastomosis with diverting loop ileostomy, showing a rising trend from 5.3% in 2012 to 8.4% in 2020. Primary anastomosis with diverting loop ileostomy patients, compared to Hartmann's procedure, had similar demographics and fewer severe comorbidities. Primary anastomosis with diverting loop ileostomy exhibited lower rates of major adverse events (24.6% vs 29.3%, P =.001). After risk adjustment, primary anastomosis with diverting loop ileostomy had similar risks of major adverse events and 30-day mortality compared to Hartmann's procedure. While having lower odds of respiratory (adjusted odds ratio 0.61, 95% confidence interval 0.45–0.83) and infectious (adjusted odds ratio 0.78, 95% confidence interval 0.66–0.93) complications, primary anastomosis with diverting loop ileostomy was associated with a 36-minute increment in operative duration and increased odds of 30-day readmission (adjusted odds ratio 1.30, 95% confidence interval 1.07–1.57) compared to Hartmann's procedure. Primary anastomosis with diverting loop ileostomy displayed comparable odds of major adverse events compared to Hartmann's procedure in acute complicated diverticulitis while mitigating infectious and respiratory complication risks. However, primary anastomosis with diverting loop ileostomy was associated with longer operative times and greater odds of 30-day readmission. Evolving guidelines and increasing primary anastomosis with diverting loop ileostomy use suggest a shift favoring primary anastomosis, especially in complicated diverticulitis. Future investigation of disparities in surgical approaches and patient outcomes is warranted to optimize acute diverticulitis care pathways. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The clinical frailty scale (CFS) evaluates the level of frailty based on clinical examination, comorbidities, and functional and activity levels of older patients. However, there are many difficulties for internists in evaluating frailty with this scale. Therefore, simplifying the CFS with good design and application is required for better treatment outcomes. Our study was conducted to design and evaluate the correlation of a simplified clinical frailty scale (sCFS) with CFS in older patients. PATIENTS AND METHODS: We undertook a cross-sectional analysis involving 279 older patients, which comprised two steps. Step 1 involves the implementation of sCFS, a protocol that has been endorsed by the Geriatrics Professional Council (GPC). Step 2 entails the enrollment of older patients for frailty assessment using sCFS, comparing it with CFS. RESULTS: The study was conducted on 279 older patients; the average age was 75.7 ± 8.4 (years old), and men accounted for 34.8%. There was a high correlation between the sCFS and CFS (Pearson's r = 0.996; p < 0 .001). The similarity of the sCFS to the CFS was very high, with Kappa coefficient = 0.984 (p < 0.001). Compared with the CFS, the sCFS had a Youden index of 98% with 100% sensitivity and 98% specificity assessed through the receiver operating characteristic (ROC) with the CFS threshold of 5. CONCLUSIONS: The sCFS can be used to assess frailty with high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Blood gas analysis is a diagnostic tool to evaluate the partial pressures of gas in blood and acid-base content. The use of blood gas analysis enables a clear understanding of respiratory, circulatory, and metabolic disorders. The arterial blood gas (ABG) explicitly analyzes blood taken from an artery, assessing the patient's partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2) pH (acid/base). PaO2 indicates the oxygenation status, and PaCO2 indicates the ventilation status (chronic or acute respiratory failure). PaO2 is affected by hyperventilation, characterized by rapid or deep breathing, and hypoventilation, characterized by slow or shallow breathing. The acid-base balance tested by the ABG procedure measures the pH and PaCO2 directly, while the use of the Hasselbach equation gives the serum bicarbonate (HCO3) and base deficit or excess. The measured HCO3 is based on a strong alkali that frees all CO2 in serum, including dissolved CO2, carbamino compounds, and carbonic acid. The calculation uses a standard chemistry analysis, giving the amount of "total CO2"; the difference will amount to around 1.2 mmol/L. Though ABG is frequently ordered in emergency medicine contests for acute conditions, it may also be needed in other clinical settings. The ABG analysis shows to be an exceptional diagnostic tool, including the group of diseases known as acid-base diseases (ABDs), which include a great variety of conditions such as severe sepsis, septic shock, hypovolemic shock, diabetic ketoacidosis, renal tubular acidosis, chronic respiratory failure, chronic heart failure, and diverse metabolic diseases. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Prognostic models proposed for cirrhotic patients' survival have not been satisfactorily investigated in the Vietnam population, especially in the medium-term period. PATIENTS AND METHODS: In this prospective study, we enrolled a total of 904 patients admitted to Hepato-Gastroenterology Center, Bach Mai Hospital from December 2019 to November 2021 and calculated their CP, MELD, MELD-Na score, IMELD, Refit MELD, and Refit MELD-Na after 2-year follow-up to compare their survival prognosis. RESULTS: The mean age of the patients was 53.8 ±10.8 years, and males constituted 91%. Compared with the surviving group, deceased patients had statistically significant lower albumin, higher INR, serum bilirubin, and creatinine levels with higher means of all prognostic scores. RefitMELD score had the highest AUC (0.768), followed by MELD (0.766), and the lowest belonged to RefitMELDNa (0.669). CONCLUSIONS: In conclusion, deceased patients had significantly higher values of Child-Pugh score and all MELD-based scores than survival. RefitMELD is the most reliable scoring system to predict 2-year mortality in patients with decompensated liver cirrhosis. [ABSTRACT FROM AUTHOR]

To investigate the incidence of venous thromboembolism (VTE) in patients undergoing large specimen hysterectomy for benign indications. To evaluate the impact of route of surgery and operative time in the development of VTE in this population. Retrospective cohort study (Canadian Task Force Classification II2) of targeted hysterectomy data prospectively collected from the American College of Surgeons National Surgical Quality Improvement Program involving over 500 hospitals across the United States. National Surgical Quality Improvement Program Database. Women aged 18 years or older undergoing hysterectomy for benign indications between 2014 and 2019. Patients were further classified into 4 groups according to uterine weight: <100 g, 100–249 g, 250 g–499 g, and specimens ≥500 g. Current Procedural Terminology codes were used to identify cases. Variables including age, ethnicity, body mass index, smoking status, diabetes, hypertension, blood transfusion, and American Society of Anesthesiologists classification system scores were collected. Cases were stratified by route of surgery, operative time, and uterine weight. A total of 122,418 hysterectomies occurring between 2014 and 2019 were included in our study, of which 28,407 (23.2%) patients underwent abdominal, 75,490 (61.7%) laparoscopic, and 18,521 (15.1%) vaginal hysterectomy. The overall rate of VTE in patients with large specimen hysterectomies (≥500 g) was 0.64%. After multivariable adjustment, there was no significant difference in the odds of VTE between uterine weight groups. Only 30% of the surgeries with uterine weight above 500 g were performed with minimally invasive surgical routes. Patients who underwent minimally invasive hysterectomy had lower odds of VTE via laparoscopic (adjusted odds ratio [aOR] 0.62; confidence interval [CI]: 0.48–0.81) and vaginal (aOR 0.46; CI: 0.31–0.69) routes compared to laparotomy. Prolonged operative time (>120 min) was associated with increased odds of VTE (aOR 1.86; CI:1.51–2.29). The occurrence of VTE after a benign large specimen hysterectomy is rare. The odds of VTE is higher with longer operative times and lower with minimally invasive approaches, even for markedly enlarged uteri. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of this study was to determine the predictive performance and compatibility of CHA2DS2-VASc-HS scores and Framingham risk scores (FRS) in patients with coronary angiography. PATIENTS AND METHODS: This cross-sectional analysis study enrolled 98 patients with ischemic heart disease who were indicated for invasive coronary angiography. Sensitivity and specificity were determined using the cut-off values of the ROC curve. The Gensini score was used to evaluate the correlation. RESULTS: The cut-off value of the Congestive heart failure, hypertension, age 75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, sex category - hyperlipidemia, smoking (CHA2DS2-VASc-HS) score was 2.5, and for FRS, it was 14.5. The area under the curve (95% CI) for the CHA2DS2-VASc-HS score and FRS were 0.76 (0.66, 0.85) and 0.80 (0.71, 0.85), respectively. For every 1-point increase in the CHA2DS2-VASc-HS score, the Gensini score increased by 0.44 (r = 0.56; R2 = 0.19, Beta = 0.44, p < 0.01), and the number of stenosis coronary branches increased by 0.55 (r = 0.56; R2 = 0.30, Beta = 0.55, p < 0.01). For every 10-point increase in FRS, the Gensini score increased by 3.8 (r = 0.57; R2 = 0.14, Beta = 0.38, p < 0.01), and the number of stenosis coronary branches increased by 5 (r = 0.53; R2 = 0.25, Beta = 0.5, p < 0.01). CONCLUSIONS: Our study demonstrated a high predictive performance of coronary artery injury using the CHA2DS2-VASc-HS score and Framingham risk scores. These scores could be applied in predicting ischemic heart disease in non-symptomatic cases where invasive coronary angiography is not indicated. [ABSTRACT FROM AUTHOR]

Background: Data collection and cleaning procedures to exclude bot-generated responses are used to maintain the data integrity of samples from online surveys. However, these procedures may be time-consuming and difficult to implement. Thus, we aim to evaluate the validity of a single-step geolocation algorithm for recruiting eligible gay, bisexual, and men who have sex with men in Philadelphia for an online study. Methods: We used a 4-step approach, based on common practices for evaluating bot-generated and fraudulent responses, to assess the validity of participants' Qualtrics survey data as our referent standard. We then compared it to Qualtrics' single-step geolocation algorithm that used the MaxMind commercial database to map participants' Internet protocol address to their approximate location. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the single-step geolocation approach relative to the 4-step approach. Results: There were 826 respondents who completed the survey and 440 (53%) were eligible for enrollment based on the 4-step approach. The single-step geolocation approach yielded a sensitivity of 91% (95% CI = 88%, 93%), specificity of 79% (95% CI = 74%, 83%), PPV of 83% (95% CI = 80%, 86%), and NPV of 88% (95% CI = 85%, 91%). Conclusions: Geolocation alone provided a moderately high level of agreement with the 4-step approach for identifying geographically eligible participants in the online sample, but both approaches may be subject to additional misclassification. Researchers may want to consider multiple procedures to ensure data integrity in online samples. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Our study aimed to evaluate the effect of soft tissue regeneration in nude mice using grafts made from the combination of adipocytes from fat tissue mesenchymal stem cells and fibrin gel from peripheral blood. MATERIALS AND METHODS: Mesenchymal stem cells were isolated from adipose tissue and identified according to ISCT criteria. The scaffold used was fibrin obtained from peripheral blood. The grafts in this study were generated by transferring mesenchymal stem cells onto a fibrin scaffold. Two types of grafts, the research sample (fibrin scaffold containing adipocytes differentiated from mesenchymal stem cells) and the control sample (fibrin scaffold only), were grafted under the dorsal skin of the same mouse. After each research period, samples were collected and evaluated by histological methods to observe the existence and growth of cells inside the grafts. RESULTS: The results showed that the study group's graft integrated better within the tissue when compared with the control group. In addition, the grafts in the study group showed the presence of cells with characteristic morphology of adipocytes one week after transplantation. In contrast, control samples showed dimorphous shapes and features mainly composed of non-homogenous fragments. CONCLUSIONS: These initial conclusions might be considered a first step in generating safe bio-compatible engineered grafts specifically usable in post-traumatic tissue regeneration procedures. [ABSTRACT FROM AUTHOR]

Data collection has suggested a complex correlation between the gut microbiota (GM) and bone homeostasis involving host-microbiota crosstalk. Although the GM is known to affect bone metabolism, the mechanisms linked with these effects remain unclear. The aim of this review is to current insight advances regarding how gut-derived hormones regulate bone homeostasis in humans, emphasizing gut-bone axis and bone regeneration. The GM may be engaged in bone metabolism and fracture risk. Additional investigations of the fundamental microbiota-related pathways in bone metabolism may uncover treatment strategies and enable the prevention of osteoporosis. A better knowledge of gut hormones' action on bone homeostasis may lead to new strategies for preventing and treating skeletal frailty related to age. [ABSTRACT FROM AUTHOR]

• Superconductivity of SnO 2 -added Bi 1.6 Pb 0.4 Sr 2 Ca 2 Cu 3 O 10+δ ceramics was investigated using resistivity measurements under magnetic fields. • Analysis of excess conductivity using Aslamazov–Larkin and Lawrence–Doniach models revealed optimized c-axis coherence length and interlayer coupling strength. • The activation energy (U 0) and upper critical field (B c2) were significantly enhanced for the x = 0.002 sample, indicating improved flux pinning properties. • Vortex phase (B-T) diagrams showed extended pinning regimes for the x = 0.002 sample, highlighting superior flux pinning characteristics. The superconducting vortex phase diagram of (Bi 1.6 Pb 0.4 Sr 2 Ca 2 Cu 3 O 10-δ) 1-x (SnO 2) x ceramics, where x = 0, 0.002, 0.004, 0.006, 0.008, and 0.010, was investigated using resistivity measurement under magnetic fields. If the value of the offset critical temperature (T c,offset) monotonously decreased on the SnO 2 -added samples, then the mean-field critical temperature (T mf) would slightly improve on the x = 0.002 sample. The excess conductivity of all samples was analyzed based on the Aslamazov–Larkin and Lawrence–Doniach models. The c -axis coherence length at 0 K (ξ c (0)) and the interlayer coupling strength were optimized on the x = 0.002 sample. The activation energy (U 0) calculated using the Arrhenius model was also increased, and the maximum for the x = 0.002 sample was reached. The upper critical field (B c2) deduced using the Werthamer–Helfand–Hohenberg model was also enhanced for the x = 0.002 sample. The small bundle field (B sb), large bundle field (B lb), irreversibility field (B irr), and B c2 were combined for the vortex phase (B-T) diagram of the x = 0.000 and x = 0.002 samples. All pinning regimes of the x = 0.002 sample were extended, clearly revealing the improvements in the flux pinning properties in that sample. [ABSTRACT FROM AUTHOR]

Background: In suspected bloodstream infections, accurate blood culture results are critical to timely diagnoses and appropriate antibiotic administration.Aim: An Initial Specimen Diversion Device®, Steripath® (Magnolia Medical Technologies, Seattle, WA, USA) was evaluated for efficacy in reducing blood culture contamination at Brooke Army Medical Center (6.8% six-month contamination rate prior to intervention) in a six-month quality improvement project.Methods: Blood cultures in the emergency department were collected using either Steripath or the standard method. Blood samples of 20 mL were cultured into an aerobic and anaerobic medium and incubated for five days using an automated microbial detection system immediately after collection. Positive bottles were Gram-stained and plated. Rapid molecular polymerase chain reaction identification was performed on all first positive bottles within a blood culture set for each admission or ED visit. Speciation was deduced during antimicrobial sensitivity testing using the Vitek-2 instrument.Findings: Seven out of 1016 (0.69%) contamination events occurred when using Steripath vs 53 out of 800 (6.6%) contamination events when using the standard method. Steripath use was associated with a 90% lower incidence of blood culture contamination vs the standard method. Post study, Steripath use was implemented as standard practice hospital-wide, and a retrospective data analysis attributed a 31.4% decrease in vancomycin days of therapy to Steripath adoption.Conclusion: Using Steripath significantly decreased blood culture contamination events for bacterial bloodstream infections compared to the standard method. Subsequent adoption of Steripath reduced overall vancomycin usage. With widescale implementation Steripath could bolster antibiotic stewardship, mitigating antibiotic resistance caused by unnecessary antibacterial treatments. [ABSTRACT FROM AUTHOR]

Mechanics of defects in solids across a wide span of length scales is commonly formulated using the dislocations theory. This paper revisits the classical problem of interaction between an elastic edge dislocation and a circular cavity. A heuristic, yet, mechanistic approach is taken to obtain the stress solution to this problem. The approach uses complex variable theory of elasticity, along with method of images. For this purpose, a definition and formulation of elastic dipole singularities similar to dipole charges in electrostatics is developed. It is shown that an image dislocation with Burger's vector of the same strength as the real dislocation but in opposite direction, as well as a set of four singularities including a dislocation dipole, a moment-dilatation dipole, and two centers of dilatation would establish a circular, traction-free boundary in an infinite elastic medium. Adding a Volterra dislocation to the finite-length edge dislocation from this study would recover the related problem of interaction between an infinite-length edge dislocation and circular cavity. The interesting analogy between the considered elastic problem and the electrostatic problem of interaction between a line electric charge and a cylindrical conductor is discussed. [ABSTRACT FROM AUTHOR]

OBJECTIVE: A new pandemic coronavirus causing coronavirus disease-2019 (COVID-19), initially called 2019-nCoV and successively named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The COVID-19 refers to the disease while the SARS-CoV-2 refers to the virus and is characterized by a rapid contagious capacity able to spread worldwide in a very short time. The rise in the number of infected patients and deaths is of great concern especially because symptoms are vague and similar to other forms of flu infection and corona syndrome infections characterized by fever, fatigue, dry cough, and dyspnea. According to the latest guidelines published by the World Health Organization (WHO), the diagnosis of COVID-19 must be confirmed by quantitative reverse transcription polymerase chain reaction (rRT-PCR) or gene sequencing of specimen obtained from throat, sputum and blood samples. However, the limitations due to logistics, as well as low sensitivity and specificity diagnostic tools currently available have been reported as the main cause of high incidence of either false-negative or positive results. PATIENTS AND METHODS: The purpose of the present translational research protocol is to discuss and present the original findings from our research team on new diagnostic technique to detect four Coronaviridae family members (SARS-CoV-2, SARS-CoV, HCoV and MERSCoV), highlighting the methodology, the procedure and the possible advantages. Moreover, the authors review the current epidemiology, precautions and safety measures for health personnel to manage patients with known or suspected COVID-19 infection. RESULTS: Implementation of an effective and rapid plan of diagnosing, screening and checking is a key factor to reduce and prevent further transmission. This procedure based on rRT-PCR could be of great help to decisively validate the results obtained from more conventional diagnostic procedures such as chest computed tomography (CT) imaging and chest ultrasound. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The clinical use of mesenchymal stem cells (MSCs) in regenerative medicine either in tissue repair or tissue reconstruction has given highly interesting results thanks to their particular nature. Sources that have attracted the attention of medical scientists from where stem cells (SCs) in adults could be obtained are different and, dental tissues have certainly become an optimal source of MSCs. Dental tissue is a main reservoir of two types of MSCs dental bud (DBSCs) that constitute the immature precursor of the tooth and dental pulp (DPSCs) that are derived from dental inner pulp and partly from dental follicle tissue and can differentiate into several cell phenotypes as osteoblast, chondrocyte, hepatocytes, cardiomyocytes, neuron and β cells. PATIENTS AND METHODS: Normal impacted third molars and tooth buds were collected from adults and adolescents underwent to extractions for orthodontic reasons. The expression of the five stemness genes Nanog, OCT4, Sox2, c-Myc and Klf4 were investigated by qRT-PCR in two different dental stem/progenitor cells: dental pulp stem cells (DPSCs) and stem cells from dental bud (DBSCs), differentiated toward osteoblastic phenotype and not. RESULTS: Both DPSCs and DBSCs are easy to access and we found their expression of the typical mesenchymal stemness makers and osteogenic capacity due to the effective presence of embryonic gene regulators like Nanog, OCT4, Sox2, c-Myc and Klf4. Both DBSCs and DPSCs could represent a valid tool in regenerative medicine and translational applications. CONCLUSIONS: The results depicted here provide, for the first time to our knowledge, a comparative outcome about the stemness properties generated from accessible tissues such as DPSCs and DBSCs. These two types of SCs showed few different distinctive genetic traits supposedly in relation to their origin, location and stage of maturation. Certainly these SCs reserve solid potential for human clinical application in autologous procedure for bone, hard tissue and soft tissue regeneration, easy to isolate, ready availability, high-biocompatibility and safety and no ethical restrictions. [ABSTRACT FROM AUTHOR]

A cell’s insoluble microenvironment has increasingly been shown to exert influence on its function. In particular, matrix stiffness and adhesiveness strongly impact behaviors such as cell spreading and differentiation, but materials that allow for independent control of these parameters within a fibrous, stromal-like microenvironment are very limited. In the current work, we devise a self-assembling peptide (SAP) system that facilitates user-friendly control of matrix stiffness and RGD (Arg-Gly-Asp) concentration within a hydrogel possessing a microarchitecture similar to stromal extracellular matrix. In this system, the RGD-modified SAP sequence KFE-RGD and the scrambled sequence KFE-R DG can be directly swapped for one another to change RGD concentration at a given matrix stiffness and total peptide concentration. Stiffness is controlled by altering total peptide concentration, and the unmodified base peptide KFE-8 can be included to further increase this stiffness range due to its higher modulus. With this tunable system, we demonstrate that human mesenchymal stem cell morphology and differentiation are influenced by both gel stiffness and the presence of functional cell binding sites in 3D culture. Specifically, cells 24 hours after encapsulation were only able to spread out in stiffer matrices containing KFE-RGD. Upon addition of soluble adipogenic factors, soft gels facilitated the greatest adipogenesis as determined by the presence of lipid vacuoles and PPARγ-2 expression, while increasing KFE-RGD concentration at a given stiffness had a negative effect on adipogenesis. This three-component hydrogel system thus allows for systematic investigation of matrix stiffness and RGD concentration on cell behavior within a fibrous, three-dimensional matrix. Statement of Significance Physical cues from a cell’s surrounding environment—such as the density of cell binding sites and the stiffness of the surrounding material—are increasingly being recognized as key regulators of cell function. Currently, most synthetic biomaterials used to independently tune these parameters lack the fibrous structure characteristic of stromal extracellular matrix, which can be important to cells naturally residing within stromal tissues. In this manuscript, we describe a 3D hydrogel encapsulation system that provides user-friendly control over matrix stiffness and binding site concentration within the context of a stromal-like microarchitecture. Binding site concentration and gel stiffness both influenced cell spreading and differentiation, highlighting the utility of this system to study the independent effects of these material properties on cell function. [ABSTRACT FROM AUTHOR]