Candidates For Repair Research Articles

ARISE: First-In-Human Evaluation of a Novel Stent Graft to Treat Ascending Aortic Dissection

Background: Operative mortality for type A aortic dissection is still 10–20% at centers of excellence. Additionally, 10–20% are not considered as viable candidates for open surgical repair and not offered life-saving emergency surgery. ARISE is a multicenter investigation evaluating the novel GORE® Ascending Stent Graft (ASG; Flagstaff, AZ). Objective: The purpose of this study is to assess early feasibility of using these investigational devices to treat ascending aortic dissection. Methods: This a prospective, multicenter, non-randomized, single-arm study that enrolls patients at high surgical risk with appropriate anatomical requirements based on computed tomography imaging at 7 of 9 US sites. Devices are delivered transfemorally under fluoroscopic guidance. Primary endpoint is all-cause mortality at 30 days. Secondary endpoints include major adverse cardiovascular and cerebrovascular events (MACCE) at 30 days, 6 months, and 12 months. Results: Nineteen patients were enrolled with a mean age of 75.7 years (range 47–91) and 11 (57.9%) were female. Ten (52.6%) had DeBakey type I disease, and the rest were type II. Sixteen (84.2%) of the patients were acute. Patients were treated with safe access, (7/19 (36.8%) percutaneous, 10/19 (52.6%) transfemoral, 2/19 (10.5%) iliac conduit), delivery, and deployment completed in all cases. Median procedure time was 154 mins (range 52–392) and median contrast used was 111 mL (range 75–200). MACCE at 30 days occurred in 5 patients including mortality 3/19 (15.8%), disabling stroke in 1/19 (5.3%), and myocardial infarction in 1/19 (5.3%). Conclusion: Results from the ARISE early feasibility study of a specific ascending stent graft device to treat ascending aortic dissection are promising.

Nano-calcium silicate mineralized fish scale scaffolds for enhancing tendon-bone healing.

Tendon-bone healing is essential for an effective rotator cuff tendon repair surgery, however, this remains a significant challenge due to the lack of biomaterials with high strength and bioactivity. Inspired by the high-performance exoskeleton of natural organisms, we set out to apply natural fish scale (FS) modified by calcium silicate nanoparticles (CS NPs) as a new biomaterial (CS-FS) to overcome the challenge. Benefit from its “Bouligand” microstructure, such FS-based scaffold maintained excellent tensile strength (125.05 MPa) and toughness (14.16 MJ/m3), which are 1.93 and 2.72 times that of natural tendon respectively, allowing it to well meet the requirements for rotator cuff tendon repair. Additionally, CS-FS showed diverse bioactivities by stimulating the differentiation and phenotypic maintenance of multiple types of cells participated into the composition of tendon-bone junction, (e.g. bone marrow mesenchymal stem cells (BMSCs), chondrocyte, and tendon stem/progenitor cells (TSPCs)). In both rat and rabbit rotator cuff tear (RCT) models, CS-FS played a key role in the tendon-bone interface regeneration and biomechanical function, which may be achieved by activating BMP-2/Smad/Runx2 pathway in BMSCs. Therefore, natural fish scale -based biomaterials are the promising candidate for clinical tendon repair due to their outstanding strength and bioactivity.

Risk factors for readmission after open abdominal aortic aneurysms repair and its outcome in chronic kidney disease patients.

Readmission after vascular procedures is a burden to hospitals and the Medicare system. Therefore, identifying risk factors leading to readmission is vital. We examined the frequency of and risk factors for 30-day readmission after open aneurysm repair (OAR) and explored post-operative outcomes with special attention for those with preexisting chronic kidney disease (CKD). Patients who underwent OAR were identified in the National Readmission Database (2016-2018). Demographic information and comorbidities were collected. Patients readmitted within 30days after their index hospitalization were identified and compared to patients without readmission records. A total of 5090 patients underwent OAR during the study timeframe with 488 patients (9.6%) were readmitted within 30days. Females were more readmitted than males (F = 11.1% vs M = 9.0%, P < 0.001). Readmitted patients had more comorbidities (median ECI 12, P < 0.05), were on Medicare (73.7%, P < 0.001), had higher surgery admission cost ($146,844, P < 0.001), longer length of stay (8days, P < 0.001), and were discharged to a lower level care facility (62.7%, P < 0.001). Comorbidities that predisposed patients for readmission include: peripheral arterial disease (OR 2.15, P < 0.01), asthma (OR 1.87, P < 0.01), chronic heart failure (OR 1.74, P < 0.05). On readmission visit, acute renal failure (23.8%) was the most common diagnosis, while intestinal surgery (13.7%) was the most common procedure. Patients with CKD (n = 968, 18.9% of total population) had double the mortality rate compared to non-CKD patients on surgery admission (10.4%, P < 0.001) and readmission (10.1%, P < 0.001). Certain factors were noted to increase readmission rate, special attention need to be paid when dealing with such group of patients requiring OAR. Vascular surgeons should meticulously weigh benefits and risks when considering OAR in patients with CKD who are not a candidate for endovascular repair, and optimize their kidney function before considering such approach.

Massive or irreparable rotator cuff tears

Aims: Massive or Irreparable rotator cuff tears are a challenging problem. There are several treatment options, but determining the correct treatment for each patient can be difficult. The author’s treatment algorithm is outlined in Figure 1 Methods: Patients without anterosuperior escape should initially be treated with physical therapy for anterior deltoid training. Results and Conclusions: In patients who fail physical therapy, or have escape, it is important to determine if the patient’s primary complaint is pain or weakness, and to determine if the patients is able to elevate their arm above horizontal on exam. If a patient has pain, and is not able to elevate their arm, then the authors have found an injection of local anesthesia and steroids can be helpful in determining true pseudoparalysis from pain inhibition. Patients with pain who are able to elevate either before or after an injection are excellent candidates for arthroscopic debridement or partial repair, biceps tenotomy, and possibly suprascapular nerve release. Patients who complain of weakness in external rotation, but have elevation to horizontal and an intact subscapularis are ideally suited for a latissumus transfer. Those with an irreparable subscapularis, but an intact superior cuff without escape are candidates for a pectoralis major transfer. Patients with arthritis on their radiographs in the setting of an irreparable rotator cuff tear, but are still able to elevate, are excellent candidates for hemiarthroplasty is indicated. Patients with true psuedoparalysis are best treated with the reverse shoulder prosthesis.

Umbilical hernia repair in patients with cirrhosis: who, when and how to treat.

Hernia management in patients with cirrhosis is a challenging problem, where indication, timing and type of surgery have been a subject of debate. Given the high risk of morbidity and mortality following surgery, together with increased risk of recurrence, a wait and see approach was often advocated in the past. The purpose of this review was to provide an overview of crucial elements in the treatment of patients with cirrhosis and umbilical hernia. Perioperative ascites control is regarded as the major factor in timing of hernia repair and is considered the most important factor governing outcome. This can be accomplished by either medical treatment, ascites drainage prior to surgery or reduction of portal hypertension by means of a transjugular intrahepatic portosystemic shunt (TIPS). The high incidence of perioperative complications and inferior outcomes of emergency surgery strongly favor elective surgery, instead of a "wait and see" approach, allowing for adequate patient selection, scheduled timing of elective surgery and dedicated perioperative care. The Child-Pugh-Turcotte and MELD score remain strong prognostic parameters and furthermore aid in identifying patients who fulfill criteria for liver transplantation. Such patients should be evaluated for early listing as potential candidates for transplantation and simultaneous hernia repair, especially in case of umbilical vein recanalization and uncontrolled refractory preoperative ascites. Considering surgical techniques, low-quality evidence suggests mesh implantation might reduce hernia recurrence without dramatically increasing morbidity, at least in elective circumstances. Preventing emergency surgery and optimizing perioperative care are crucial factors in reducing morbidity and mortality in patients with umbilical hernia and cirrhosis.

Accelerated Discovery of the Polymer Blends for Cartilage Repair through Data-Mining Tools and Machine-Learning Algorithm.

In designing successful cartilage substitutes, the selection of scaffold materials plays a central role, among several other important factors. In an empirical approach, the selection of the most appropriate polymer(s) for cartilage repair is an expensive and time-consuming affair, as traditionally it requires numerous trials. Moreover, it is humanly impossible to go through the huge library of literature available on the potential polymer(s) and to correlate the physical, mechanical, and biological properties that might be suitable for cartilage tissue engineering. Hence, the objective of this study is to implement an inverse design approach to predict the best polymer(s)/blend(s) for cartilage repair by using a machine-learning algorithm (i.e., multinomial logistic regression (MNLR)). Initially, a systematic bibliometric analysis on cartilage repair has been performed by using the bibliometrix package in the R program. Then, the database was created by extracting the mechanical properties of the most frequently used polymers/blends from the PoLyInfo library by using data-mining tools. Then, an MNLR algorithm was run by using the mechanical properties of the polymers, which are similar to the cartilages, as the input and the polymer(s)/blends as the predicted output. The MNLR algorithm used in this study predicts polyethylene/polyethylene-graftpoly(maleic anhydride) blend as the best candidate for cartilage repair.

Novel β-TCP/HA biphasic calcium phosphate microspheres with porous surface structure prepared via a calcium carbonate template

Calcium phosphate-based materials have been considered and widely developed as a promising candidate for bone repair and regeneration. With an aim to allow a better balance between resorption and degradation, novel beta-tricalcium and hydroxyapatite (β-TCP/HA) biphasic calcium phosphate (BCP) microspheres with different surface topographies were successfully prepared in this study. Results revealed that the surface topography structure of prepared BCP microspheres could be adjusted by tuning phosphoric acid concentrations and pH values. In vitro cytocompatibility has also been evaluated by CCK-8 and live/dead staining. Moreover, the potential applications of the obtained BCP microspheres as drug delivery were investigated by using the doxycycline as a model drug. All the results have demonstrated that utilizing the spherical calcium carbonate as a hard template is an effective strategy for synthesizing advanced β-TCP/HA BCP microspheres with controllable surface topography, which holds tremendous promise for bone regeneration and drug delivery applications.

Transcatheter Repair In Patients With Functional Mitral Regurgitation From The CLASP Study: Outcomes To 2 Years

<h3>Background</h3> Transcatheter mitral valve repair is a favorable option in patient care for treating functional mitral regurgitation (FMR). We report 2-year outcomes from the FMR group of the multicenter, prospective, single arm CLASP study with the PASCAL transcatheter valve repair system. <h3>Methods</h3> Patients with symptomatic FMR ≥3+ deemed candidates for transcatheter repair by the local heart team were eligible. Follow-up was conducted to two years with echocardiographic outcomes evaluated by the core laboratory at all timepoints; other outcomes included major adverse events (MAEs) evaluated by an independent clinical events committee to one year (site-reported thereafter); six-minute walk distance (6MWD) and quality of life evaluated to one year. <h3>Results</h3> Eighty-five FMR patients were treated; mean age 72 years, 55% male, 65% in NYHA Class III-IVa, mean LVEF 37%, and 100% ≥3+ MR. Successful implantation was achieved in 96% of patients. MAEs included one cardiovascular mortality (1.2%) and one conversion to mitral valve replacement surgery (1.2%) at 30 days, and two reinterventions between 30 days and two years. Kaplan-Meier (KM) estimates for survival were 88% at one year and 72% at two years. Freedom from heart failure (HF) rehospitalization was 81% at one year and 78% at two years. Reduction in annualized HF hospitalization rate was 81% (p<0.001). MR ≤1+ was achieved in 73% of patients at 30 days, 75% at one year, and 84% at two years; MR ≤2+ was achieved in 96% of patients at 30 days, 100% at one year, and 95% at two years (all p<0.001). Mean LVEDV of 199 mL at baseline decreased by 9 mL at 30 days (p=0.039), 29 mL at one year (p<0.001), and 31 mL at two years (p<0.001). NYHA class I-II was achieved in 87% of patients at 30 days, 86% at one year, and 88% at two years (all p<0.001). Average 6MWD improved by 22 m at 30 days (p=0.004) and 40 m at one year (p=0.003). Kansas City Cardiomyopathy Questionnaire (KCCQ) score improved by 16 points at 30 days and one year (all p<0.001). <h3>Conclusions</h3> : The PASCAL transcatheter valve repair system demonstrated sustained favorable outcomes at two years in patients with FMR. Results showed a high survival rate of 72% and freedom from HF rehospitalization of 78% with an 81% reduction in annualized HF hospitalization rate. Sustained MR reduction of MR ≤2+ was achieved in 95% and MR ≤1+ in 84% of patients, with evidence of left ventricular reverse remodeling. Improvements in functional status were clinically significant and durable. The CLASP IIF randomized pivotal trial (NCT03706833) is ongoing.

Influence of Simulated Oral Conditions on Different Pretreatment Methods for the Repair of Glass-Ceramic Restorations.

The present study investigated the influence of simulated intraoral conditions (increased temperature and humidity) on two different surface pretreatment methods to repair a lithium-disilicate glass-ceramic (LDS). A total of 540 rectangular lithium-disilicate glass-ceramic bars were manufactured (3 x 7 x 9 mm; IPS e.max CAD, Ivoclar Vivadent). Further specimen preparation was performed in an incubator with controlled relative humidity (RH) and temperature to simulate three different environmental settings: laboratory conditions (LC, n = 180, 23°C, 50% RH), rubber-dam conditions (RC, n = 180, 30°C, 50% RH) or oral conditions (OC, n = 180, 32°C, 95 ± 5% RH). One-third of the bars under each condition (n = 60) were grit blasted (GBL) with alumina (35 µm at 1 bar pressure for 10 s and a working distance of 4 ± 1 cm) and primed (60 s, Monobond Plus, Ivoclar Vivadent). Another third (n = 60) were pretreated with a self-etching glass-ceramic primer (MEP, Monobond Etch & Prime, Ivoclar Vivadent). One group without surface pretreatment (n = 60, NoPT) served as a control. All pretreated surfaces were coated with Heliobond (Ivoclar Vivadent). Two bars from the same pretreatment method were luted perpendicular to each other with a resin composite to form a square adhesion area of 9 mm2 (TetricEvo Ceram, Ivoclar Vivadent), and light cured for 20 s on each side (1200 mW/cm2, Bluephase 20i, Ivoclar Vivadent). All specimens were stored for 24 h in distilled water at 37°C. Half of the specimens from each environmental setting and pretreatment method (n = 15) were thermocycled (TC, 5000 cycles, 5/55°C, 30-s dwell time), and tensile bond strength (TBS) testing was performed for all groups using an x-bar rope-assisted set-up. Data were statistically analyzed using two-way ANOVA (a = 0.05) with Bonferroni adjustment. Regardless of the environmental and storage conditions (24 h or TC), MEP showed a significantly higher mean TBS than GBL. A decrease in TBS was recorded in specimens under OC compared to RC and LC for both pretreatment methods independent of the storage condition. No significant difference in mean TBS was found between RC and LC within the MEP pretreatment group for the 24 h stored and thermocycled specimens. For all MEPs and GBLs, TC reduced the mean TBS in all environmental conditions. The NoPT groups showed no adhesion regardless of environmental or storage conditions. Increased temperature and high humidity significantly reduced TBS. However, MEP was less sensitive to environmental influences than GBL, which makes it a promising candidate for intraoral ceramic repair. These findings suggest that clinical intraoral repair of lithium-disilicate glass-ceramics should be performed using a rubber-dam, primarily when using GBL.

Understanding who benefits from endovascular aortic repair in those deemed unfit for open repair

IntroductionPatients with abdominal aortic aneurysms (AAAs) who are deemed unacceptable candidates for open repair (UNFIT) pose a clinical challenge. The EVAR2 Trial randomized UNFIT patients to endovascular aortic repair (EVAR) vs no intervention from 1999 to 2003, concluding that survival was not improved by EVAR. However, outcomes after EVAR over the last 2 decades have dramatically changed. Thus, the purpose of this study was to evaluate outcomes after EVAR in UNFIT patients using more contemporary data and to determine which subsets of UNFIT patients may potentially benefit from EVAR. MethodsThe Vascular Quality Initiative database (2003-2020) was used to identify elective EVARs for AAAs. Patients were categorized as UNFIT or suitable (SUITABLE) for open repair by the operative surgeon. Predicted 1-year mortality of untreated AAAs was calculated via a modified Gagne Index adjusted for AAA size. The primary outcome for the study was 30-day mortality. Secondary outcomes included perioperative major adverse cardiac events (a composite of clinically significant arrhythmia, congestive heart failure, and myocardial infarction), length of stay, and 1-year mortality. ResultsA total of 31,471 patients met study criteria with 27,036 (85.9%) deemed SUITABLE and 4435 (14.1%) UNFIT. UNFIT patients were more likely to experience a perioperative major adverse cardiac event (5.1% vs 2.2%, P < .001) and had longer lengths of stay (1 day [interquartile range, 1-3 days] vs 1 day [interquartile range, 1-2 days], P < .001). The 30-day mortality was significantly higher for UNFIT patients (0.8% vs 0.4%, P < .001). UNFIT patients had worse 1-year survival compared with SUITABLE patients. However, UNFIT and SUITABLE patients had significantly improved actual 1-year mortality with EVAR compared with predicted 1-year mortality without EVAR: 9.5% vs 15.6% (P < .001) and 4.0% vs 11.7% (P < .001), respectively. The mortality benefit after EVAR in UNFIT patients was primarily restricted to those with smaller Gagne Indices and larger aneurysm diameters. Patients deemed unsuitable for open repair due to frailty or multiple reasons had significantly higher 30-day mortality rates after EVAR when compared with SUITABLE patients (1.3% vs 1.6% vs 0.4%, P < .001). Those deemed unsuitable for open repair due to frailty or multiple reasons had worse 1-year cumulative survival compared with all other UNFIT patients. ConclusionsDespite being high risk with higher perioperative morbidity and mortality, UNFIT patients have lower actual 1-year mortality with EVAR than predicted 1-year mortality without EVAR. However, this potential benefit is reserved to those with small Gagne Indices, larger AAA diameters, and lack of frailty.

Recent Developments in Hyaluronic Acid-Based Hydrogels for Cartilage Tissue Engineering Applications.

Articular cartilage lesions resulting from injurious impact, recurring loading, joint malalignment, etc., are very common and encompass the risk of evolving to serious cartilage diseases such as osteoarthritis. To date, cartilage injuries are typically treated via operative procedures such as autologous chondrocyte implantation (ACI), matrix-associated autologous chondrocyte implantation (MACI) and microfracture, which are characterized by low patient compliance. Accordingly, cartilage tissue engineering (CTE) has received a lot of interest. Cell-laden hydrogels are favorable candidates for cartilage repair since they resemble the native tissue environment and promote the formation of extracellular matrix. Various types of hydrogels have been developed so far for CTE applications based on both natural and synthetic biomaterials. Among these materials, hyaluronic acid (HA), a principal component of the cartilage tissue which can be easily modified and biofunctionalized, has been favored for the development of hydrogels since it interacts with cell surface receptors, supports the growth of chondrocytes and promotes the differentiation of mesenchymal stem cells to chondrocytes. The present work reviews the various types of HA-based hydrogels (e.g., in situ forming hydrogels, cryogels, microgels and three-dimensional (3D)-bioprinted hydrogel constructs) that have been used for cartilage repair, specially focusing on the results of their preclinical and clinical assessment.

Anatomic Repair of Congenitally Corrected Transposition: Reappraisal of Eligibility Criteria

Several criteria to identify suitable candidates for anatomic repair in congenitally corrected transposition (cc-TGA) have been proposed. The purpose of this study was to critically re-evaluate adequacy of these recommendations in our patient cohort. All cc-TGA patients undergoing anatomic repair between 2010 and 2019 were reviewed. Evaluated eligibility criteria for repair included age ≤ 15 years, LV mass index ≥ 45–50 g/m2, LV mass/volume ratio > 0.9–1.5 and systolic LV to right ventricle pressure ratio > 70–90% among others. Repair failure was defined as postoperative early mortality or LV dysfunction requiring mechanical circulatory support. Twenty-five patients were included (median [interquartile range] age at surgery 1.8 years [0.7;6.6]; median postoperative follow-up 3.2 years [0.7;6.3]). Median preoperative LV ejection fraction was 60% [56;64], indexed LV mass 48.5 g/m2 [43.7;58.1] and LV mass/volume ratio 1.5 [1.1;1.6], respectively. A total of 12 patients (48%) did not meet at least one of the previously recommended criteria, however, all but two patients (92%) experienced favorable early outcome. Of 7 patients (28%) with indexed LV mass < 45 g/m2, 6 were successfully operated. There were two early repair failures (8%) with LV dysfunction: one patient died and one required mechanical circulatory support but recovered well. Surgery was performed successfully in patients with LV mass and volume Z-scores as low as − 2 and − 2.5, respectively. Anatomic correction for cc-TGA can be performed with excellent early outcome and is feasible even in patients with LV mass below previously recommended cut-offs. The use of LV mass and volume Z-scores might help to refine eligibility criteria.

Transcriptome Sequencing Reveals Key Genes in Three Early Phases of Osteogenic, Adipogenic, and Chondrogenic Differentiation of Bone Marrow Mesenchymal Stem Cells in Rats.

Bone mesenchymal stem cells (BMSCs) of multi-directional differentiation and reproductive activity are attractive candidates for bone and cartilage repair. However, the molecular mechanisms underlying the early phase of osteogenesis, adipogenesis, and chondrogenesis of BMSCs are still far from understood. In the current study, BMSCs are isolated from rats, and the gene expressions during the initiation of differentiation (phase I), lineage acquisition (phase II), and early lineage progression (phase III) of three-directional differentiation of BMSCs were detected by using high-throughput sequencing. Then, 356, 540, and 299 differentially expressed genes (DEGs) were identified in phases I, II, and III of osteogenesis, respectively. The numbers are 507, 287, and 428 for adipogenesis, respectively, and 412, 336, and 513 for chondrogenesis, respectively. Time-dependent expression patterns of genes were also validated during three-directional differentiation in BMSCs. Hub genes including Ccna2, Cdc20, and Il6 may act as common participants in initiating osteogenesis, adipogenesis, and chondrogenesis. Mex3b, Sertad1, and Hopx showed an enhanced expression throughout three early phases during the osteogenic differentiation but no significant change in other two-directional differentiation. A similar pattern of Dtx4 and Ibsp expression occurred in adipogenesis and chondrogenesis, respectively. Our findings will help understand the underlying mechanism determining the differentiation fate of BMSCs and provide theoretical support for the clinical treatment of osteoporosis, osteoarthritis, and other age-related bone diseases.

A Vascularized Conductive Elastic Patch for the Repair of Infarcted Myocardium through Functional Vascular Anastomoses and Electrical Integration

AbstractConductive cardiac patches have been proven to promote angiogenesis in infarcted myocardium; however, their conductive integrity, elasticity, and vascularization potential have not yet been optimized. The prevascularization of conductive elastic cardiac patches could be an effective strategy for building a substantial connection between the patch and the infarcted heart. Here, a coronary artery casting is introduced into a holey graphene oxide/polypyrrole‐incorporated polyhydroxyethyl methacrylate prefabricated gel to form a vascularized conductive elastic patch. The engineered patches are able to rebuild functional vascular anastomoses and provide strong electrical integration with infarcted hearts, resulting in effective myocardial infarction repair in vivo. RNA sequencing analyses further reveal that the conductive elastic patches under dynamic culture conditions upregulated cardiac muscle contraction‐ and ATP biosynthesis‐related mRNA expression in vitro. Together, this study demonstrates that the fabricated patches have versatile conductivity, elasticity, and vascularization properties, and could therefore be a promising candidate for heart repair.

Contemporary Management of Abdominal Aortic Aneurysms.

Abdominal aortic aneurysms (AAA) can carry extremely high mortality rates and most will only present with symptoms with impending rupture. We present an overview of management of this disease process starting with screening, to medical management, surveillance and treatment options currently available, as well as those being studied for future use. Screening has been proven to reduce the mortality rate. There still remains a paucity of data to support medical therapies to help mitigate the rate of aneurysm growth and prevent rupture. However, on the topic of repair, there have been advancements in endovascular devices which have broadened the scope of treatment for patients with anatomy not amenable to standard endovascular repair or those who are not suitable candidates for open surgical repair. Appropriate surveillance, risk factor modification, and operative repair, when indicated, are the cornerstones of contemporary management of AAAs. Advancements in endovascular technologies have allowed us to treat more patients. Further research is warranted on non-operative medical therapies.

Osteoporotic bone recovery by a bamboo-structured bioceramic with controlled release of hydroxyapatite nanoparticles.

While most bone defects can be repaired spontaneously, the healing process can be complicated due to insufficient bone regeneration when osteoporosis occurs. Synthetic materials that intrinsically stimulate bone formation without inclusion of exogenous cells or growth factors represent a highly desirable alternative to current grafting strategies for the management of osteoporotic defects. Herein, we developed a series of hydroxyapatite bioceramics composed of a microwhiskered scaffold (wHA) reinforced with multiple layers of releasable hydroxyapatite nanoparticles (nHA). These novel bioceramics (nwHA) are tunable to optimize the loading amount of nHA for osteoporotic bone formation. The utility of nwHA bioceramics for the proliferation or differentiation of osteoporotic osteoblasts in vitro is demonstrated. A much more compelling response is seen when bioceramics are implanted in critical-sized femur defects in osteoporotic rats, as nwHA bioceramics promote significantly higher bone regeneration and delay adjacent bone loss. Moreover, the nwHA bioceramics loaded with a moderate amount of nHA can induce new bone formation with a higher degree of ossification and homogenization. Two types of osteogenesis inside the nwHA bioceramic pores were discovered for the first time, depending on the direction of growth of the new bone. The current study recommends that these tailored hybrid micro/nanostructured bioceramics represent promising candidates for osteoporotic bone repair.

Risk factors for adverse outcomes in emergency versus nonemergency open umbilical hernia repair and opportunities for elective repair in a national cohort of patients with cirrhosis

BackgroundWhether to perform umbilical hernia repair in patients with cirrhosis is a common dilemma for surgeons. We aimed to determine the incidence, morbidity, and mortality associated with emergency and nonemergency umbilical hernia repair in patients with and without cirrhosis, and to explore opportunities for nonemergency repair. MethodsVeterans diagnosed with cirrhosis between 2001 and 2014 and a frequency-matched sample of veterans without cirrhosis were followed through September 2017. Veterans Affairs Surgical Quality Improvement Program data provided outcomes and risk factors for mortality after umbilical hernia repair. We performed chart review of a random sample of patients undergoing emergency umbilical hernia repair. ResultsAmong 119,605 veterans with cirrhosis and 118,125 matched veterans without cirrhosis, the Veterans Affairs Surgical Quality Improvement Program database included 1,475 and 552 open umbilical hernia repairs, respectively. In patients with cirrhosis, 30-day mortality was 1.2% after nonemergency umbilical hernia repair and 12.2% after emergency umbilical hernia repair, contrasting with zero deaths in patients without cirrhosis undergoing these repairs. In patients with cirrhosis but no ascites in the prior month, 30-day mortality after nonemergency umbilical hernia repair was 0.7%, compared to 2.2% in those with ascites. Chart review of patients requiring emergency umbilical hernia repair revealed that elective umbilical hernia repair may have been feasible in 30% of these patients in the prior year; fewer than half of those undergoing emergency umbilical hernia repair had received a general surgery consultation in the prior 2 years. ConclusionsNonemergency open umbilical hernia repair was associated with relatively low perioperative mortality in patients with cirrhosis and no recent ascites. About 30% of patients undergoing emergency umbilical hernia repair may have been candidates for nonemergency repair in the prior year.

The Effect of Internal Mesh Fixation and External Fixation (Inguinal Hernia Truss) on Postoperative Complications in Patients with Inguinal Hernia Undergoing Totally Extraperitoneal Laparoscopic Hernioplasty.

Background:The present study evaluated the effect of internal mesh fixation and external fixation (inguinal hernia truss) on postoperative complications in patients with inguinal hernia.Materials and Methods:This randomized clinical trial was performed on 64 patients that were candidates for inguinal hernia repair by laparoscopic method following the totally extraperitoneal procedure. These patients were randomly divided into two groups. In the first group, the mesh was fixed with a maximum of three absorbable tacks. In the second group, the inguinal hernia truss was used as the external fixation for 6 weeks immediately after the surgery.Results:The results revealed that seroma, neuralgia, and recurrence were observed with the values of 6.4%, 19.4%, and 3.2% in Group A and 3.3%, 13.3%, and 3.3% in Group B (P > 0.05). Moreover, patients’ pain scores 1 week and 1 month after the surgery in Group B were significantly lower than those of Group A (P < 0.05). However, the mean pain score of patients was not different between the two groups 3 and 6 months after the surgery (P > 0.05). Furthermore, the duration of return to work in Group B with an average of 8.07 ± 3.09 days was less than that of Group A with the average of 9.65 ± 5.34 days (P > 0.05).Conclusion:The mentioned findings can trigger the use of external fixation and an inguinal hernia truss as a support for the abdominal wall to make the dream of not using a foreign body in the human body come true.

Dexmedetomidine alleviates oxygen and glucose deprivation-induced apoptosis in mesenchymal stem cell via downregulation of MKP-1

Bone marrow mesenchymal stem cell (MSC)-based therapy is a novel candidate for heart repair. But ischemia-reperfusion injury leads to low viability of MSC. Dexmedetomidine (Dex) has been found to protect neurons against ischemia-reperfusion injury. It remains unknown if Dex could increase the viability of MSCs under ischemia. The present study is to observe the potential protective effect of Dex on MSCs under ischemia and its underlying mechanisms. Specific mRNAs related to myocardial ischemia in the GEO database were selected from the mRNA profiles assessed in a previous study using microarray. The most dysregulated mRNAs of the specific ones from the above study were subject to bioinformatics analysis at our laboratory. These dysregulated mRNAs possibly regulated apoptosis of cardiomyocytes and were validated in vitro for their protective effect on MSCs under ischemia. MSCs were pre-treated with Dex at 10 μM concentration for 24 h under oxygen-glucose deprivation (OGD). Flow cytometry and TUNEL assay were carried out to detect apoptosis in Dex-pretreated MSCs under OGD. The relative expressions of mitogen-activated protein kinase phosphatase 1 (MKP-1) and related genes were detected by quantitative polymerase chain reaction and western blotting. Microarray data analysis revealed that Dex regulates MAPK phosphatase activity. Dex significantly reduced in vitro apoptosis of MSCs under OGD, which suppressed the synthesis level of Beclin1 and light chain 3 proteins. Dex down-regulated MKP-1 expression and attenuated an OGD-induced change in the mitogen activated protein kinase 3 (MAPK3) signaling pathway. Dex increases the viability of MSC and improves its tolerance to OGD in association with the MKP-1 signaling pathway, thus suggesting the potential of Dex as a novel strategy for promoting MSCs efficacy under ischemia.

Glutaraldehyde: Introducing Optimum Condition for Cross-linking the Chitosan/Gelatin Scaffolds for Bone Tissue Engineering

Large bone defects caused by trauma or disease needs extra intervention. Gelatin/chitosan complex is one of the most valuable compositions for bone healing, but fast degradation in aqueous solution and low mechanical properties increase the need for cross-linking agent. The cross-linker concentration and cross-linking method had a significant effect on the properties of fabricated scaffolds. Here, three different cross-linking methods of Glutaraldehyde (GA), including addition to the solution, vapor exposure, and immersion, were studied by different in-vitro analyses to find the best GA cross-linker concentration and cross-linking method. Scanning electron microscopy showed homogeneous microstructures in all samples. Fourier transform infrared spectrophotometry revealed cross-linking reactions in all samples. Swelling ratio and biodegradation ratio was reduced by increasing cross-linking concentration and exposure time. Nonetheless, higher cross-linker concentration and exposure time improved mechanical properties, while it seems the cross-linking exposure time had more effect than concentration. Accordingly, GA (1 wt%) cross-linked scaffold with solution addition method showed suitable performance with 39.3° contact angle, 1.45±0.05 MPa compressive strength, 22.31±1.3 (%) swelling ratio, and 26.33±4.47 (%) biodegradation ratio. In-vitro experiments indicated cells were spread all over the scaffolds with higher than 80 (%) cell viability in all time points. The expression of alkaline phosphatase (ALP) and osteo-related genes (osteocalcin and related transcription factor 2) were improved during 14 days of cell incubation and showed the high capacity of the scaffold support in mineralization and osto-differentiation. Therefore GA (1 wt% ) cross-linked scaffold with solution addition was introduced as the best candidate for bone repair and further studies.