Diclofenac and metformin synergistic dose dependent inhibition of hamster fibrosarcoma, rescued with mebendazole.

We examined whether combinig diclofenac and metformin in doses equivalent to human doses would synergize their anticancer activity on fibrosarcoma inoculated to hamsters and in vitro. Rescue experiment was performed to examine whether the prosurvival NF-κB stimulation by mebendazole can reverse anticancer effects of the treatment. BHK-21/C13 cell culture was subcutaneously inoculated to Syrian golden hamsters randomly divided into groups (6 animals per group): 1) untreated control; treated daily with 2) diclofenac; 3) metformin; 4) combinations of diclofenac and metformin at various doses; 5) combination of diclofenac, metformin and mebendazole; 6) mebendazole. Dose response curves were made for diclofenac and metformin combination. Tumor growth kinetics, biophysical, pathological, histological and immunohistochemical characteristics of excised tumors and hamster organs as well as biochemical and hematological blood tests were compared among the groups. Single treatments had no anticancer effects. Diclofenac (60 mg/kg/day) exhibited significant (P < 0.05) synergistic inhibitory effect with metformin (500 mg/kg/day) on all tumor growth parameters, without toxicity and influence on biochemical and hematological blood tests. The same results were obtained with double doses of diclofenac and metformin combination. The addition of mebendazole to the diclofenac and metformin combination rescued tumor expansion. Furthermore, diclofenac with metformin demonstrated antiproliferative effects in hamster fibrosarcoma BHK-21/C13, human lung carcinoma A549 (CCL-185), colon carcinoma HT-29 (HTB-38) and cervical carcinoma HeLa (CCL-2) cell cultures, with markedly lower cytotoxicity in the normal fetal lung MRC-5 cells. In conclusion, diclofenac and metformin combination may be recommended for potential use in oncology, due to synergistic anticancer effect in doses achievable in humans.

Modeling a well-characterized perfluorooctane sulfonate (PFOS) source and plume using the REMChlor-MD model to account for matrix diffusion.

Two of the most important retention processes for per- and polyfluoroalkyl substances (PFAS) in groundwater likely are sorption and matrix diffusion. The objective of this study was to model concentration and mass discharge of one PFAS, perfluorooctane sulfonate (PFOS), with matrix diffusion processes incorporated using data from a highly chemically- and geologically-characterized site. When matrix diffusion is incorporated into the REMChlor-MD model for PFOS at this research site, it easily reproduces the field data for three key metrics (concentration, mass discharge, and total mass). However, the no-matrix diffusion model produced a much poorer match. Additionally, after about 40 years of groundwater transport, field data and the REMChlor-MD model both showed the majority (80%) of the measured PFOS mass that exited the source zones was located in downgradient low permeability zones due to matrix diffusion. As such, most of the PFOS mass is not available to immediately migrate downgradient via advection in the more permeable sands at this site, which has important implications for monitored natural attenuation (MNA). Plume expansion over the next 50 years is forecasted to be limited, from a 350-m plume length in 2017 to 550 m in 2070, as matrix diffusion will attenuate groundwater plumes by slowing their expansion. This phenomenon is important for constituents that do not degrade, such as PFOS, compared to those susceptible to degradation. Overall, this work shows that matrix diffusion is a relevant process in environmental PFAS persistence and slows the rate of plume expansion over time.

Disulfiram and metformin combination anticancer effect reversible partly by antioxidant nitroglycerin and completely by NF-κB activator mebendazole in hamster fibrosarcoma.

We investigated the anticancer effect of disulfiram and metformin combination on fibrosarcoma in hamsters. Hamsters of both sexes (~ 70 g) were randomly allocated to control and experimental groups (8 animals per group). In all 10 groups, 2 × 106 BHK-21/C13 cells in 1 ml were injected subcutaneously into the animals' backs. Peroral treatments were carried out with disulfiram 50 mg/kg daily, or with metformin 500 mg/kg daily, or with their combination. Validation and rescue grups were treated by double doses of the single therapy and by the combination with addition of rescue daily doses of ROS inhibitor nitroglycerin 25 mg/kg or NF-κB stimulator mebendazole 460 mg/kg, via a gastric probe after tumor inoculation. After 19 days all animals were sacrificed. Blood samples were collected for hematological and biochemical analyses, the tumors were excised and weighed, and their diameters and volumes were measured. The tumor samples were pathohistologically and immunohistochemically assessed (Ki-67, PCNA, CD34, CD31, COX4, Cytochrome C, GLUT1, iNOS), and the main organs were toxicologically tested. The combination of disulfiram and metformin significantly inhibited fibrosarcoma growth in hamsters without toxicity, compared to monotherapy or control. The single treatments did not show significant antisarcoma effect. Co-treatment with nitroglycerin partly rescued tumor progression, probably by ROS inhibition, while mebendazole completely blocked anticancer activity of the disulfiram and metformin combination, most likely by NF-κB stimulation. Combination of disulfiram with metformin may be used as an effective and safe candidate for novel nontoxic adjuvant and relapse prevention anticancer therapy.

Tranexamic Acid Has No Effect on Postoperative Hemarthrosis or Pain Control After Anterior Cruciate Ligament Reconstruction Using Bone-Patellar Tendon-Bone Autograft: A Double-Blind, Randomized, Controlled Trial.

PURPOSE: The purpose of this double-blind, randomized, controlled trial was to evaluate the use of intravenous (IV) tranexamic acid (TXA) in patients undergoing primary bone-patellar tendon-bone (BPTB) anterior cruciate ligament reconstruction (ACLR) regarding postoperative hemarthrosis, pain, opioid consumption, and quadriceps atrophy and activation. METHODS: A controlled, randomized, double-blind trial was conducted in 110 patients who underwent ACLR with BPTB autograft. Patients were equally randomized to the control and experimental groups. The experimental group received two 1-g boluses of IV TXA, one prior to tourniquet inflation and one prior to wound closure; the control group did not receive TXA. If a clinically significant hemarthrosis was evident, the knee was aspirated and the volume of blood (in milliliters) was recorded. Additionally, we recorded perioperative blood loss (in milliliters); visual analog scale scores on postoperative days 1, 4, and 7 and at postoperative weeks 1, 6, and 12; postoperative opioid consumption on postoperative days 1, 4, and 7; range of motion (ROM) and ability to perform a straight leg raise at postoperative weeks 1, 6, and 12; and preoperative and postoperative thigh circumference ratio. RESULTS: There was no significant difference in perioperative blood loss between the TXA and control groups (32.5 mL vs 35.6 mL, P = .47). In the TXA group, 23 knees were aspirated; in the control group, 26 knees were aspirated (P = .56). No significant difference in postoperative hemarthrosis volume was seen in patients who received IV TXA versus those who did not (26.7 mL vs 37.3 mL, P = .12). There was no significant difference in visual analog scale scores between the 2 groups (P = .15); in addition, there was no difference in postoperative opioid consumption (P = .33). No significant difference in ROM, ability to perform a straight leg raise, or postoperative thigh circumference ratio was observed (P > .05 for all). CONCLUSIONS: IV TXA in patients who undergo ACLR with BPTB autograft does not significantly impact perioperative blood loss, postoperative hemarthrosis, or postoperative pain levels. Additionally, no significant differences were seen in early postoperative recovery regarding ROM or quadriceps reactivation. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Evaluation of a drop-in waste volume reduction method for liquid investigation derived waste containing per- and polyfluoroalkyl substances.

Development of on-site treatment strategies for PFAS-containing investigation derived waste (IDW) will decrease the potential for secondary release following off-site disposal, lower disposal costs, and promote more effective long-term management of PFAS-laden waste. Herein, we report the application of a simple, drop-in treatment that utilizes one of two PFAS sorbents: bituminous granular activated carbon (GAC) or strong base anion exchange resin (IX) and a small circulation pump to adsorb and concentrate PFAS impacted mass from liquid IDW collected from two sites with disparate water chemistries and synthetic IDW amended with PFAS-containing aqueous film forming foam (AFFF). Bench scale intermittent circulation experiments revealed that bituminous granular activated carbon (GAC, 0.5 mg/mL) removed up to 97.0 ± 1.4% and 96.4 ± 0.5% of PFOS and PFOA, respectively, in both site-derived IDW sources. Improved performance was observed in experimental treatments containing a strong base anion exchange resin (IX, 0.5 mg/mL), where up to 99.4 ± 0.1% and 96.7 ± 0.2% of PFOS and PFOA were removed, respectively. High chloride concentrations (20 g/L) reduced removal of short chain perfluorocarboxylates (PFBA and PFHxA) using GAC or IX, but high salt concentrations had negligible effects on the removal of PFOA, PFBS, PFHxS, or PFOS. Excellent scalability was observed in mesoscale experiments, where the majority of amended PFAS mass was removed from synthetic IDW within five days of vessel circulation using two different PFAS-capture configurations. Combined PFOS and PFOA concentrations were reduced to levels below 0.07 µg/L using either GAC or IX for both configurations. Results generated in this study support the application of this approach as an economical strategy for potential waste volume reduction in IDW destined for off-site disposal.

Mass-Based, Field-Scale Demonstration of PFAS Retention within AFFF-Associated Source Areas.

Transport of poly- and perfluoroalkyl substances (PFAS) at aqueous film-forming foam (AFFF)-impacted sites is limited by various processes that can retain PFAS mass within the source area. This study used concentration data obtained via a high-resolution sampling and analytical protocol to estimate the PFAS mass distribution in source and downgradient areas of a former firefighter training area. The total PFAS mass present at the site was approximately 222 kg, with 106 kg as perfluoroalkyl acids (PFAAs) and 116 kg as polyfluorinated precursors. Zwitterionic and cationic PFAS represented 83% of the total precursor mass and were found primarily in the source and up/side-gradient areas (75%), likely due to preferential hydrophobic partitioning, electrostatic interactions, and diffusion into lower-permeability soils. Based on the release history and the high percentage of total PFAS mass represented by precursors (primarily electrochemical fluorination-derived compounds), the estimated conversion rate of precursors to PFAAs was less than 2% annually. Eighty-two percent of the total PFAS mass was encountered in lower-permeability soils, which limited the potential for advection and transformation. This contributed to a 99% decrease in the mass discharge rate at the far-downgradient plume (0.048 kg/yr compared to the near-source area (3.6 kg/yr)). The results provide field-scale evidence of the importance of these PFAS retention processes at sites where AFFF has been released.

Enhancing xylose and glucose utilization as well as solvent production using a simplified three-electrode potentiostat system during Clostridium fermentation.

A simple potentiostat was constructed as a strategy to enhance solvent production in a mediatorless and oxygen-exposed fermentation inoculated with the aerotolerant strain Clostridium sp. C10. Elevated n-butanol and acetone titers were recorded in all fermentations with either glucose or xylose in the presence of electrodes poised at + 500 mV (+ 814 mV vs SHE) relative to cells plus substrate only controls. Respective butanol titers and volumetric butanol productivities in studies performed with 30 g/L glucose or 30 g/L xylose were 1.67 and 2.27 times and 1.90 and 6.13 times greater in the presence of electrodes compared to controls. Glucose and xylose utilization in the presence of electrodes was 61 and 125% greater than no-electrode controls, respectively. Increasing substrate concentrations to 60 g/L decreased the butanol yields relative to the studies performed at 30 g/L. These data suggest that it may be more efficient to alter reactor reduction potential than increase substrate concentration for solvent output during industrial fermentations, which favors higher yield with few additional inputs.

Co-treatment with nitroglycerin and metformin exhibits physicochemically and pathohistologically detectable anticancer effects on fibrosarcoma in hamsters.

We investigated the effect of nitroglycerin with metformin on fibrosarcoma in hamsters. Syrian golden hamsters of both sexes, weighing approximately 60 g, were randomly allocated to control and experimental groups, with 8 animals per group. In all groups, 2 × 106 BHK-21/C13 cells in 1 ml were injected subcutaneously into the animals' backs. Peroral treatment carried out with nitroglycerin 25 mg/kg daily, or with metformin 500 mg/kg daily, or with a combination of nitroglycerin 25 mg/kg and metformin 500 mg/kg daily. Later validation experiments were conducted with double doses of the single therapy and additional rescue doses of mebendazole 460 mg/kg daily, via a gastric probe after tumor inoculation. After 2 weeks, when the tumors were approximately 2-3 cm in the control group, all animals were sacrificed. Blood samples were collected for hematological and biochemical analyses, the tumors were excised and weighed, and their diameters and volumes were measured. The tumor samples were pathohistologically and immunohistochemically assessed for proliferation marker protein Ki-67, proliferating cell nuclear antigen PCNA, hematopoietic progenitor cell antigen CD34, cluster of differentiation 31 (CD31), cytochrome c oxidase subunit 4 (COX4), mitochondria marker Cytochrome C, glucose transporter 1 (GLUT1) and inducible nitric oxide synthase (iNOS), and the main organs were toxicologically tested. The Ki-67 and PCNA positivity and the cytoplasmic marker (CD34, CD31, COX4, Cytochrome C, GLUT1, iNOS) immunoexpression in the tumor samples were quantified. The combination of nitroglycerin and metformin significantly inhibited fibrosarcoma growth in hamsters without toxicity, compared to monotherapy or control. The results were validated and confirmed in the subsequently accomplished experiment with doubled doses of the single drug therapy and in the rescue experiment with addition of mebendazole. The single treatments did not show significant antisarcoma effect, regardless of the dose. Co-treatment with mebendazole inhibited anticancer activity of the nitroglycerin and metformin combination. Mebendazole rescued tumor progression suppressed by the combination of nitroglycerin and metformin. Administration of nitroglycerin with metformin might be an effective and safe approach in novel nontoxic adjuvant and relapse prevention anticancer treatment.

Impact of Angiotensin-converting Enzyme and Matrix Metalloproteinase-3 Gene Polymorphisms on Risk for Developing Vascular Access Failure in Hemodialysis Patients - A Pilot Study.

For adequate hemodialysis, functional vascular access is obligatory. Neointimal hyperplasia (NIH) has a central role in stenosis and thrombosis development, which represent the most frequent causes of vascular access failure. Polymorphism of different genes that have a significant role in endothelial function may have an impact on NIH development. Therefore, the aim of our study is to determine the effect of angiotensin-converting enzyme (ACE) I/D and matrix metalloproteinase-3 (MMP3) 5A/6A polymorphism on risk for developing vascular access failure in hemodialysis patients. The study included 200 patients on regular hemodialysis at Nephrology Department, University Medical Center Zvezdara. Retrospective analysis included a collection of general and vascular access data from medical records. Genetic analysis was performed by using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Patients were divided into two groups: Group 1-patients who have never experienced vascular access failure and Group 2-patients who have at least one spontaneous vascular access failure. There was no difference in age, gender, hemodialysis vintage, main diagnosis, presence of hypertension, and diabetes mellitus between the two groups. There were no statistically significant differences in the frequencies of ACE and MMP3 genotypes between the two groups. Without statistical significance, it was found that homozygotes for I allele had two times higher risk for developing vascular access failure than homozygotes for D allele (OR 2.00; 95%CI: 0.727-5.503; P = 0.180). In addition, patients with 5A allele have 1.7 times higher risk for developing vascular access failure compared with patients without this allele (OR 1.745; 95% CI: 0.868-3.507; P = 0.118). Patients with vascular access failure do not have different genotype distribution regarding ACE gene and MMP3 gene polymorphism as compared with patients without vascular access failure. Still, homozygotes for I allele and homozygotes for 5A allele have higher risk for developing vascular access failure compared with other patients.

Physicochemical and pathohistological changes in experimental fibrosarcoma tumors of hamsters treated with metformin and itraconazole.

The anticancer effects of metformin (an antihyperglycaemic agent) and itraconazole (an antifungal agent), which are established non-oncologic drugs, were investigated in the present study. The weight, diameter, volume, density, surface, surface to volume ratio and immunohistochemistry of experimental fibrosarcoma tumors were investigated in hamsters treated with metformin and itraconazole. Briefly, the hamsters were injected with BHK-21/C13 cells in order to induce fibrosarcoma, and the animals were treated daily with metformin, itraconazole or a combination of the two drugs. Subsequently, blood samples were obtained for biochemical analyses and the tumors were excised, weighed and measured. The tumor samples were pathohistologically and immunohistochemically assessed for proliferation marker protein Ki-67, hematopoietic progenitor cell antigen CD34, cytochrome c oxidase subunit 4 (COX4), glucose transporter 1 (GLUT1) and inducible nitric oxide synthase (iNOS), and vital organs were toxicologically tested. Ki-67-positivity and cytoplasmic marker (CD34, COX4, GLUT1, iNOS) immunoexpression in the tumor samples were quantified. The results revealed that the combination of metformin and itraconazole significantly altered the physicochemical and pathohistological characteristics of the hamster fibrosarcoma tumors, including absolute and relative weight, volume, density, length, surface area, surface to volume ratio, Ki-67-positivity and the immunoexpression of cytoplasmic markers, without indications of toxicity. Furthermore, metformin with itraconazole demonstrated antiproliferative functions in cervical carcinoma HeLa, colon carcinoma HT-29, lung carcinoma A549 and fibrosarcoma BHK-21/C13 cells, with markedly lower cytotoxicity in the normal fetal lung MRC-5 cells. In conclusion, the administration of metformin in combination with itraconazole may inhibit the growth of fibrosarcoma tumors in vivo and the proliferation of various malignant cell lines in vitro, suggesting that this may be an effective and safe approach as a nontoxic anticancer adjuvant and relapse prevention therapy.

Review of core-multishell nanostructured models for nano-biomedical and nano-biopharmaceutical application.

The main advantage of a theoretical approach is essential knowledge of the mechanisms that allow us to comprehend the experimental conditions that we have to fulfill to be able to get the desired results. Based on our research in ultrathin crystal structures performed so far, superlattices, Q-wires and Q-dots, we will consider the materials that can act as carriers for medicines and tagged substances. For this purpose we established a shell-model of ultrathin crystals and investigated their fundamental characteristics. This could be considered as a form of nano-engineering. In this paper we will analyze application of nanomaterials in biomedicine, that is to say we will present the recent accomplishments in basic and clinical nanomedicine. Achieving full potential of nanomedicine may be years or even decades away, however, potential advances in drug delivery, diagnosis, and development of nanotechnology-related drugs start to change the landscape of medicine. Site-specific targeted drug delivery (made possible by the availability of unique delivery platforms, such as dendrimers, nanoparticles and nanoliposomes) and personalized medicines (result of the advance in pharmacogenetics) are just a few concepts on the horizon of research. In this paper, especially, we have analyzed the changes in basic physical properties of spherical-shaped nanoparticles that can be made in several (nano)layers and have, at the same time, multiple applications in medicine. This paper presents a review of our current achievement in the field of theoretical physics of ultrathin films and possible ways to materialize the same in the field of nanopharmacy.

Solvent production from xylose.

Xylose is the second most abundant sugar derived from lignocellulose; it is considered less desirable than glucose for fermentation, and strategies that specifically increase xylose utilization in wild type or engineered cells are goals for biofuel production. Issues arise with xylose utilization because of carbohydrate catabolite repression, which is the preferential utilization of glucose relative to xylose in fermentations with both pure and mixed cultures. Taken together the low substrate utilization rates and solvent yields with xylose compared to glucose, many industrial fermentations ignore the xylolytic portion of the reaction in lieu of methods to maintain high glucose. This is shortsighted given the massive potential for xylose generation from a number of sustainable biomass feedstocks, based on utilization of the hemicellulose fraction(s) that enter pretreatment. A number of strategies have been developed in recent years to address xylose utilization and solvent production from xylose in systems with just xylose, or in systems with mixtures of glucose plus xylose, which are more typical of pretreated lignocellulose. The approaches vary in terms of complexity, stability, and ease of introduction to existing fermentation infrastructure (i.e., so-called drop-in fermentation strategies). Some approaches can be considered traditional engineering approaches (e.g., change the reaction conditions), while others are more subtle cellular approaches to eliminate the impacts of catabolite repression. Finally, genetic engineering has been used to increase xylose utilization, although this can be considered a relatively nascent approach compared to manipulations completed to date for glucose utilization.

Total Joint Arthroplasty in Ambulatory Surgery Centers: Analysis of Disqualifying Conditions and the Frequency at Which They Occur.

BACKGROUND: The frequency of total joint arthroplasties (TJAs) performed in ambulatory surgery centers (ASCs) is increasing. However, not all TJA patients are healthy enough to safely undergo these procedures in an ambulatory setting. We examined the percentage of arthroplasty patients who would be eligible to have the procedure performed in a free-standing ASC and the distribution of comorbidities making patients ASC-ineligible. METHODS: We reviewed the charts of 3444 patients undergoing TJA and assigned ASC eligibility based on American Society of Anesthesiologists (ASA) status, a set of exclusion criteria, and any existing comorbidities. RESULTS: Overall, 70.03% of all patients undergoing TJA were eligible for ASC. Of the ASA class 3 patients who did not meet any exclusion criteria but had systemic disease (51.11% of all ASA class 3 patients), 53.69% were deemed ASC-eligible because of sufficiently low severity of comorbidities. The most frequent reasons for ineligibility were body mass index >40 kg/m2 (32.66% of ineligible patients), severity of comorbidities (28.00%), and untreated obstructive sleep apnea (25.19%). CONCLUSION: A large proportion of TJA patients were found to be eligible for surgery in an ASC, including over one-third of ASA class 3 patients. ASC performed TJA provides an opportunity for increased patient satisfaction and decreased costs, selecting the right candidates for the ambulatory setting is critical to maintain patient safety and avoid postoperative complications.

Electron shuttling to ferrihydrite selects for fermentative rather than Fe3+ -reducing biomass in xylose-fed batch reactors derived from three different inoculum sources.

Reports suggest that ferric iron and electron shuttling molecules will select for Fe3+ -reducer dominated microbial biomass. We investigated the influence of the redox mediators anthraquinone-2,6-disulfonate (AQDS) and riboflavin using xylose as the sole fermentation substrate, with or without ferric iron. Electron shuttling to insoluble ferrihydrite enhanced solventogenesis, acidogenesis, hydrogen production, and xylose consumption, relative to the cells plus xylose controls in fermentations inoculated with woodland marsh sediment, wetwood disease, or raw septic liquid, over multiple transfers in 15-day batch fermentations. 16S rRNA gene based community analyses indicated that ferrihydrite alone, and AQDS/riboflavin plus ferrihydrite, immediately shifted native heterogeneous communities to those predominantly belonging to the Clostdridiales, rather than stimulating Fe3+ respiring populations. Data were similar irrespective of the inoculum source, suggesting that Fe3+ and/or electron shuttling compounds select for rapid proliferation of fermentative genera when fermentable substrates are present, and increases the extent of xylose consumption and solvent production.

Ferric iron and extracellular electron shuttling increase xylose utilization and butanol production during fermentation with multiple solventogenic bacteria.

Xylose is the second most abundant sugar derived from lignocellulose; it is considered less desirable than glucose for fermentation, and strategies that specifically increase xylose utilization in wild-type cells are goals for biofuel production. Xylose consumption, butanol production, and hydrogen production increased in both Clostridium beijerinckii and a novel solventogenic bacterium (strain DC-1) when anthraquinone-2,6,-disulfonate (AQDS) or riboflavin were used as redox mediators to transfer electrons to poorly crystalline Fe(OH)3 as an extracellular electron sink. Strain DC-1 was most closely related to Rhizobiales bacterium Mfc52 based on 95% 16S rRNA gene sequence similarity, which demonstrates that this response is not limited to a single genus of xylose-fermenting bacteria. Xylose utilization and butanol production were negligible in control incubations containing cells plus 3% (w/v) xylose alone during a 10-day batch fermentation, for both strains tested (n-butanol titers of 0.05 g L-1). Micromolar concentrations of AQDS and riboflavin were added as electron shuttling compounds with poorly crystalline Fe(OH)3 as an insoluble electron acceptor, and respective n-butanol titers increased to 6.35 and 7.46 g L-1. Increases in xylose consumption for the iron treatments were relatively high, from less than 0.49 g L-1 (xylose alone, no iron or electron shuttling molecules) to 25.98 and 29.15 g L-1 for the AQDS and riboflavin treatments, respectively. Hydrogen production was also 3.68 times greater for the AQDS treatment and 5.27 greater for the riboflavin treatment relative to controls. Strain DC-1 data were similar, again indicating that the effects are not specific to the genus Clostridium.

An Evaluation of Patient Risk Factors to Determine Eligibility to Undergo Orthopaedic Surgery in a Freestanding Ambulatory Center A Survey of 4,242 Consecutive Patients.

INTRODUCTION: The value proposition of surgery at freestanding ambulatory surgery centers (FSASCs) in terms of efficiency, safety, and patient satisfaction is well established and has led to increased FSASC utilization. However, there are comorbid conditions that disqualify certain patients from surgery at FSASCs. Understanding the percentage of patients whose comorbid conditions exclude them from FSASCs is important for the proper planning and utilization of operating room assets. We aim to understand the percentage of excluded patients, and we predict that certain procedures have higher rates of disqualification due to the types of patients who undergo them. METHODS: We reviewed the records of 4,242 consecutive patients undergoing outpatient orthopaedic surgeries in our hospital system from July 2015 to February 2016. Patient characteristics, comorbidities, and procedures performed were included in our database. We analyzed each case and determined eligibility for surgery at our FSASC based on established comorbidity exclusionary guidelines. Chi-square and t-tests were used to establish statistical significance. RESULTS: Of 4,242 patients, 878 (20.7%) were ineligible for surgery at our FSASC based on accepted exclusionary guidelines. The average body mass index (BMI) of FSASC-eligible patients was 27.37, compared to 31.68 for FSASC-ineligible patients (p < 0.001). The majority, 85.6% (543/634), of American Society of Anesthesiologists (ASA) class 3 patients were FSASC-ineligible. The most common reasons for excluding patients from surgery at our FSASC were morbid obesity (25.4% of ineligible cases), untreated obstructive sleep apnea (22.1%), age less than 13 (19.6%), and coronary artery disease with prior intervention (13.3%). When stratifying by procedure, the operations most likely to be FSASC-ineligible were contracture releases (39.13% ineligible, p = 0.03), trigger finger releases (36.14%, p < 0.001), carpal tunnel releases (30.63%, p = 0.009), tumor resections (38.89%, p = 0.056), rotator cuff repairs (25.47%, p = 0.078), and subacromial decompressions (30.23%, p = 0.12), primarily because these patients have more comorbidity (ASA 2.20 vs. 1.88, p < 0.001). CONCLUSIONS: Roughly 1 in 5 patients is ineligible for surgery at a freestanding ASC due to disqualifying comorbidities. Although FSASCs offer cost effective care that satisfies patients, we must understand that certain patients cannot have their surgeries at these venues. In addition, we must use additional caution when scheduling certain procedures at a FSASC. Therefore, as the number and complexity of the surgeries performed at FSASCs increase, we must better understand the factors that make patients better candidates for surgery in a hospital setting, thus minimizing transfers and readmissions and maximizing the value proposition of FSASCs.

The 5A Allele of the MMP3-Gene Promoter Polymorphism Is a Risk Factor for Poor Outcome of Hemodialysis Patients.

Cardiovascular morbidity is the leading cause of death in dialysis patients and many risk factors have been involved in its pathogenesis. Genetic susceptibility may be of importance including polymorphism for matrix metalloproteinase 3 (MMP3), which is an enzyme that catalyzes the degradation of collagen, proteoglycans, fibronectin, laminine and elastin. The MMP3 gene promoter contains an insertion/deletion polymorphism characterised by an array of 5 or 6 adenosine residues (5A/6A) at -1612 position. Literature data show that the 5A or 6A allele of the MMP3 gene shows different risk for cardiovascular and overall outcome in general population. The aim was to analyze the -1612 5A/6A promoter polymorphism in a group of hemodialysis patients and to correlate the findings with cardiovascular morbidity and 7-year all-cause and cardiovascular mortality. This study included 196 patients on hemodialysis for longer than six months at University Medical Center Zvezdara. The leading causes of end stage renal disease were hypertension and diabetes mellitus. Venous blood was collected on midweek dialysis session and genotype analysis was performed by using polymerase chain reaction-restriction fragment length polymorphism method. Among the 198 hemodialysis patients, there were 142 (72%) 5A/6A heterozygotes, 12 (6%) 5A/5A homozygotes, and 44 (22%) 6A/6A homozygotes. These data are consistent with Hardy-Weinberg equilibrium. After 7-year follow-up, the 5A homozygotes showed the lowest all-cause and cardiovascular survival, while the 6A homozygotes showed the highest cardiovascular survival. The 5A allele of the MMP3-gene promoter polymorphism is a potential risk factor in the poor outcome of hemodialysis patients.

Auricular Acupressure in the Prevention of Postoperative Nausea and Emesis A Randomized Controlled Trial.

INTRODUCTION: Successful antiemesis contributes significantly to quality, safety, and patient satisfaction. Patients undergoing general anesthesia often experience postoperative nausea and vomiting (PONV). Acupressure offers a side effect-free alternative to common first-line antiemetics. Because the patient may perceive needle acupuncture as uncomfortable, acupressure is a desirable alternative for the prevention of PONV. METHODS: This study was a randomized, prospective, double-blinded clinical trial investigating the effect of acupressure in patients with a history of PONV and motion sickness. The three auricular acupressure points chosen were shen men, point zero, and the subcortex point. Rescue treatment for PONV with 4 mg intravenous ondansetron was used if the patient reported persistent nausea. A blinded observer recorded antiemetic rescue data, and postoperative analgesic use was recorded over 24 hours. Nausea, vomiting, and retching were assessed in the post-anesthesia care unit (PACU). RESULTS: Using univariate analysis, we ruled out the null hypothesis of equal means as a function of intervention group (p = 0.001). Pair-wise comparisons revealed a difference between placebo and test groups (p = 0.000) and also sham and test groups (p = 0.033) where age (p = 0.048) and gender (p = 0.003) were significant covariates. DISCUSSION: Our data reveal that auricular acupressure significantly decreases nausea during the PACU stay and within the 24 hours postoperatively. It is not clear whether the intervention decreases nausea as a primary effect or as a secondary result by decreasing narcotic requirements. Also, perception of nausea may be in part subjective. This is evidenced by our results in which subjects who received sham points fared better than the placebo subjects.

Calcification in arteriovenous fistula blood vessels may predict arteriovenous fistula failure: a 5-year follow-up study.

PURPOSE: Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. The impact of vascular calcification process on AVF survival remains unclear and results of several studies about this issue are controversial. In the light of the new knowledge about the different susceptibility for calcification process in different blood vessels, the aim of our study was to analyze whether the calcification of AVF-blood vessels may have an impact on AVF longevity. METHODS: The study included 90 patients, 49 males and 41 females, all of them Caucasians, with a mean age 62 ± 11 years, on regular hemodialysis for more than 1 year with patent primary AVFs. Vascular calcification in AVF-blood vessels or in the anastomotic region was detected using X-ray examination. RESULTS: Calcification in AVF-blood vessels was found in 62% of patients. Binary logistic regression analysis demonstrated that male gender, presence of diabetes mellitus and longer duration of AVF before calcification determination were associated with calcification of AVF-blood vessels. Using a Cox proportional hazard model adjusted for these standardized predicted values revealed that patients with present AVF-blood vessels calcification had increased risk to develop AVF failure with a hazard rate of 3.42 (95% confidence interval 1.00-11.67; P = 0.049). CONCLUSIONS: Calcifications of AVF-blood vessels are found frequently among dialysis patients and may jeopardize the survival of native AVF. We suggested the local X-ray as simple and valid method for detection of patients that are at risk for AVFs failure which should be monitored more closely.