The effect of microbial activity on soil water diffusivity.

In this study, we explored the effects of microbial activity on the evaporation of water from cores of a sandy soil under laboratory conditions. We applied treatments to stimulate microbial activity by adding different amounts of synthetic analogue root exudates. For comparison, we used soil samples without synthetic root exudates as control and samples treated with mercuric chloride to suppress microbial activity. Our results suggest that increasing microbial activity reduces the rate of evaporation from soil. Estimated diffusivities in soil with the largest amounts of added root exudates were one third of those estimated in samples where microbial activity was suppressed by adding mercuric chloride. We discuss the effect of our results with respect to water uptake by roots. HIGHLIGHTS: We explored effects of microbial activity on the evaporation of water from cores of a sandy soil.We found the effect of microbial activity on water release characteristic was small.Increasing microbial activity reduced evaporation from soil, while microbial suppression increased it.Effect of microbial activity on root water uptake was estimated to be equivalent to a change in soil structure.

The response of osteoblastic MC3T3-E1 cells to micro- and nano-textured, hydrophilic and bioactive titanium surfaces.

The aim of the present work was to investigate the morphology and activity of the murine osteoblastic cell line MC3T3 on control smooth (Machined), commercially available rough (ZT) titanium discs, and on titanium samples obtained by modifying the ZT treatment protocol, and herein labelled as ZTF, ZTM and ZTFM. Cells were evaluated at SEM and immunofluorescence for morphology and cell-to-cell interactions and by MTT assay and real time PCR for cell growth and function. Microscopy showed that ZT modified protocols could differently affect cell shape and distribution. All the tested surfaces showed good biocompatibility by viability assay. However, cells on smoother surfaces appeared to express higher levels of transcript for Collagen 1a1, the main component of extracellular matrix, by real time PCR. Expression of the early differentiation marker Alkaline Phosphatase was higher on ZTF surfaces and ZTM enhanced the expression of later osteoblastic markers Osteoprotegerin and Osteocalcin. Noteworthy, the expression of Connexin 43, a component of cell-to-cell contacts and hemichannels, followed a similar pattern to differentiation marker genes and was higher in cells on ZTM surfaces, consistently with the microscopic observation of cell clusters. Taken together, this data showed that ZTF and ZTM treatment protocols appeared to improve the basal sand-blasting/acid-etching ZT procedure with ZTM surfaces promoting the most mature stage of differentiation.

Surface modification of Ti-6Al-4 V alloy for biomineralization and specific biological response: part II, alkaline phosphatase grafting.

Titanium and its alloys are the most widespread materials for the realization of orthopaedic and dental implants due to their good mechanical properties and biocompatibility. Surface functionalization of biomaterials aimed to improve and quicken implant integration and tissue regeneration is an active research field. The opportunity to confer biological activity (ability to directly stimulate cells with proper biological signals) to the Ti6Al4 V alloy, previously modified to be bioactive from the inorganic point of view (apatite precipitation), was explored in this research work. The alkaline phosphatase (ALP) enzyme was grafted to metal surface via tresyl chloride activation, maintaining its activity. A synergistic effect between biological functionalization and inorganic bioactivity was observed.

Surface modification of Ti-6Al-4V alloy for biomineralization and specific biological response: Part I, inorganic modification.

Titanium and its alloys represent the gold standard for orthopaedic and dental prosthetic devices, because of their good mechanical properties and biocompatibility. Recent research has been focused on surface treatments designed to promote their rapid osteointegration also in case of poor bone quality. A new surface treatment has been investigated in this research work, in order to improve tissue integration of titanium based implants. The surface treatment is able to induce a bioactive behaviour, without the introduction of a coating, and preserving mechanical properties of Ti6Al4V substrates (fatigue resistance). The application of the proposed technique results in a complex surface topography, characterized by the combination of a micro-roughness and a nanotexture, which can be coupled with the conventional macro-roughness induced by blasting. Modified metallic surfaces are rich in hydroxyls groups: this feature is extremely important for inorganic bioactivity (in vitro and in vivo apatite precipitation) and also for further functionalization procedures (grafting of biomolecules). Modified Ti6Al4V induced hydroxyapatite precipitation after 15 days soaking in simulated body fluid (SBF). The process was optimised in order to not induce cracks or damages on the surface. The surface oxide layer presents high scratch resistance.

Bioactive materials: In vitro investigation of different mechanisms of hydroxyapatite precipitation.

Bioactive materials, able to induce hydroxyapatite precipitation in contact with body fluids, are of great interest for their bone bonding capacity. . The aim of this paper is to compare bioactive materials with different surface features to verify the mechanisms of action and the relationship with kinetics and type of precipitated hydroxyapatite over time. Four different surface treatments for Ti/Ti6Al4V alloy and a bioactive glass were selected and a different mechanism of bioactivity is supposed for each of them. Apart from the conventional techniques (FESEM, XPS and EDX), less common characterizations (zeta potential measurements on solid surfaces and FTIR chemical imaging) were applied. The results suggest that the OH groups on the surface have several effects: the total number of the OH groups mainly affects hydrophilicity of surfaces, while the isoelectric points, surface charge and ions attraction mainly depend on OH acidic/basic strength. Kinetics of hydroxyapatite precipitation is faster when it involves a mechanism of ion exchange while it is slower when it is due to electrostatic effects . The electrostatic effect cooperates with ion exchange and it speeds up kinetics of hydroxyapatite precipitation. Different bioactive surfaces are able to differently induce precipitation of type A and B of hydroxyapatite, as well as different degrees of crystallinity and carbonation. STATEMENT OF SIGNIFICANCE: The bone is made of a ceramic phase (a specific type of hydroxyapatite), a network of collagen fibers and the biological tissue. A strong bond of an orthopedic or dental implant with the bone is achieved by bioactive materials where precipitation and growth of hydroxyapatite occurs on the implant surface starting from the ions in the physiological fluids. Several bioactive materials are already known and used, but their mechanism of action is not completely known and the type of precipitated hydroxyapatite not fully investigated. In this work, bioactive titanium and bioglass surfaces are compared through conventional and innovative methodologies. Different mechanisms of bioactivity are identified, with different kinetics and the materials are able to induce precipitation of different types of hydroxyapatite, with different degree of crystallinity and carbonation.

The mechanical and chemical stability of the interfaces in bioactive materials: The substrate-bioactive surface layer and hydroxyapatite-bioactive surface layer interfaces.

Bioactive materials should maintain their properties during implantation and for long time in contact with physiological fluids and tissues. In the present research, five different bioactive materials (a bioactive glass and four different chemically treated bioactive titanium surfaces) have been studied and compared in terms of mechanical stability of the surface bioactive layer-substrate interface, their long term bioactivity, the type of hydroxyapatite matured and the stability of the hydroxyapatite-surface bioactive layer interface. Numerous physical and chemical analyses (such as Raman spectroscopy, macro and micro scratch tests, soaking in SBF, Field Emission Scanning Electron Microscopy equipped with Energy Dispersive Spectroscopy (SEM-EDS), zeta potential measurements and Fourier Transformed Infra-Red spectroscopy (FTIR) with chemical imaging) were used. Scratch measurements evidenced differences among the metallic surfaces concerning the mechanical stability of the surface bioactive layer-substrate interface. All the surfaces, despite of different kinetics of bioactivity, are covered by a bone like carbonate-hydroxyapatite with B-type substitution after 28 days of soaking in SBF. However, the stability of the apatite layer is not the same for all the materials: dissolution occurs at pH around 4 (close to inflammation condition) in a more pronounced way for the surfaces with faster bioactivity together with detachment of the surface bioactive layer. A protocol of characterization is here suggested to predict the implant-bone interface stability.

Nanogrooves and keratin nanofibers on titanium surfaces aimed at driving gingival fibroblasts alignment and proliferation without increasing bacterial adhesion.

Periimplantitis and epithelial downgrowth are nowadays the main conditions associated to transmucosal dental implants. Gingival fibroblasts can play an important role in periimplantitis because they are the promoters of the inflammatory process and eventual tissue homeostasis and destruction. Moreover, the related inflammatory state is commonly driven also to counteract bacteria implants colonization. In the present research, a new technology based on mechanically produced nanogrooves (0.1-0.2µm) and keratin nanofibers deposited by electrospinning has been proposed in order to obtain titanium surfaces able to drive gingival fibroblasts alignment and proliferation without increasing bacterial adhesion. The prepared surfaces have been characterized for their morphology (FESEM), chemical composition (FTIR, XPS), surface charge (zeta potential) and wettability (contact angle). Afterwards, their performances in terms of cells (human primary gingival fibroblasts) and bacteria (Staphylococcus aureus) adhesion were compared to mirror-like polished titanium surfaces. Results revealed that gingival fibroblasts viability was not negatively affected by the applied surface roughness or by keratin nanofibers. On the opposite, cells adhesion and spread were strongly influenced by surface roughness revealing a significant cell orientation along the produced nanogrooves. However, the keratin influence was clearly predominant with respect to surface topography, thus leading to increased cells proliferation on the surfaces with nanofibers, disregarding the presence of the surfaces grooves. Moreover, nor nanogrooves nor keratin nanofibers increase bacterial biofilm adhesion in comparison with mirror polished surfaces. Thus, the present research represents a promising innovative strategy and technology for a surface modification finalized to match the main requirements for transmucosal dental implants.

How do wettability, zeta potential and hydroxylation degree affect the biological response of biomaterials?

It is well known that composition, electric charge, wettability and roughness of implant surfaces have great influence on their interaction with the biological fluids and tissues, but systematic studies of different materials in the same experimental conditions are still lacking in the scientific literature. The aim of this research is to investigate the correlations between some surface characteristics (wettability, zeta potential and hydroxylation degree) and the biological response (protein adsorption, blood wettability, cell and bacterial adhesion) to some model biomaterials. The resulting knowledge can be applied for the development of future innovative surfaces for implantable biomaterials. Roughness was not considered as a variable because it is a widely explored feature: smooth surfaces prepared by a controlled protocol were compared in order to have no roughness effects. Three oxides (ZrO2, Al2O3, SiO2), three metals (316LSS steel, Ti, Nb) and two polymers (corona treated polystyrene for cell culture and untreated polystyrene for bacteria culture), widely used for biomedical applications, were considered. The surfaces were characterized by contact profilometry, SEM-EDS, XPS, FTIR, zeta potential and wettability with different fluids. Protein adsorption, blood wettability, bacterial and cell adhesion were evaluated in order to investigate the correlations between the surface physiochemical properties and biological responses. From a methodological standpoint, XPS and electrokinetic measurements emerged as the more suitable techniques respectively for the evaluation of hydroxylation degree and surface charge/isoelectric point. Moreover, determination of wettability by blood appeared a specific and crucial test, the results of which are not easily predictable by using other type of tests. Hydroxylation degree resulted correlated to the wettability by water, but not directly to surface charge. Wetting tests with different media showed the possibility to highlight some differences among look-alike materials. A dependence of protein absorption on hydroxylation degree, charge and wettability was evidenced and its maximum was registered for surfaces with low wettability in both water based and protein containing media and a moderate surface charge. As far as bacterial adhesion is concerned, no effect of surface charge or protein adsorption was evidenced, while the presence of a high acid component of the surface energy appeared significant. Finally, the combination of hydroxylation degree, wettability, surface charge and energy (polar component) emerged as a key parameter for cell adhesion and viability.

Assessing Tn5 and Sleeping Beauty for transpositional transgenesis by cytoplasmic injection into bovine and ovine zygotes.

Transgenic domestic animals represent an alternative to bioreactors for large-scale production of biopharmaceuticals and could also provide more accurate biomedical models than rodents. However, their generation remains inefficient. Recently, DNA transposons allowed improved transgenesis efficiencies in mice and pigs. In this work, Tn5 and Sleeping Beauty (SB) transposon systems were evaluated for transgenesis by simple cytoplasmic injection in livestock zygotes. In the case of Tn5, the transposome complex of transposon nucleic acid and Tn5 protein was injected. In the case of SB, the supercoiled plasmids encoding a transposon and the SB transposase were co-injected. In vitro produced bovine zygotes were used to establish the cytoplasmic injection conditions. The in vitro cultured blastocysts were evaluated for reporter gene expression and genotyped. Subsequently, both transposon systems were injected in seasonally available ovine zygotes, employing transposons carrying the recombinant human factor IX driven by the beta-lactoglobulin promoter. The Tn5 approach did not result in transgenic lambs. In contrast, the Sleeping Beauty injection resulted in 2 lambs (29%) carrying the transgene. Both animals exhibited cellular mosaicism of the transgene. The extraembryonic tissues (placenta or umbilical cord) of three additional animals were also transgenic. These results show that transpositional transgenesis by cytoplasmic injection of SB transposon components can be applied for the production of transgenic lambs of pharmaceutical interest.

Antibacterial titanium surfaces for medical implants.

Bacterial contamination is a critical problem in different fields (ranging from everyday life to space missions, and from medicine to biosensing). Specifically, in the case of medical implants, foreign materials are preferential sites for bacterial adhesion and microbial contamination, which can lead to the development of prosthetic infections. These problems can in turn lead to the necessity of a prolonged antibiotic therapy (which can last for years) and eventually to the removal of the device, with a consequent significant increase in the hospitalization times and costs, together with a stressful, painful and critical situation for the patient. Commercially pure titanium and its alloys are the most commonly used materials for permanent implants in contact with bone, and the prevention of infections on their surface is therefore a crucial challenge for orthopaedic and dental surgeons. The problem of the bacterial contamination of medical implants is briefly described in the first part of the present review. Then the most important inorganic antibacterial agents (Ag, Cu and Zn) are described, and this is followed by a review of the reported attempts of their introduction onto the surface of Ti-based substrates.

Efficient edition of the bovine PRNP prion gene in somatic cells and IVF embryos using the CRISPR/Cas9 system.

The recently developed engineered nucleases, such as zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease (Cas) 9, provide new opportunities for gene editing in a straightforward manner. However, few reports are available regarding CRISPR application and efficiency in cattle. Here, the CRISPR/Cas9 system was used with the aim of inducing knockout and knock-in alleles of the bovine PRNP gene, responsible for mad cow disease, both in bovine fetal fibroblasts and in IVF embryos. Five single-guide RNAs were designed to target 875 bp of PRNP exon 3, and all five were codelivered with Cas9. The feasibility of inducing homologous recombination (HR) was evaluated with a reporter vector carrying EGFP flanked by 1 kbp PRNP regions (pHRegfp). For somatic cells, plasmids coding for Cas9 and for each of the five single-guide RNAs (pCMVCas9 and pSPgRNAs) were transfected under two different conditions (1X and 2X). For IVF zygotes, cytoplasmic injection was conducted with either plasmids or mRNA. For plasmid injection groups, 1 pg pCMVCas9 + 0.1 pg of each pSPgRNA (DNA2X) was used per zygote. In the case of RNA, two amounts (RNA1X and RNA2X) were compared. To assess the occurrence of HR, a group additionally cotransfected or coinjected with pHRegfp plasmid was included. Somatic cell lysates were analyzed by polymerase chain reaction and surveyor assay. In the case of embryos, the in vitro development and the genotype of blastocysts were evaluated by polymerase chain reaction and sequencing. In somatic cells, 2X transfection resulted in indels and large deletions of the targeted PRNP region. Regarding embryo injection, higher blastocyst rates were obtained for RNA injected groups (46/103 [44.6%] and 55/116 [47.4%] for RNA1X and RNA2X) than for the DNA2X group (26/140 [18.6%], P < 0.05). In 46% (26/56) of the total sequenced blastocysts, specific gene editing was detected. The total number of genetic modifications (29) was higher than the total number of gene-edited embryos, as three blastocysts from the group RNA2X reported more than one type of modification. The modifications included indels (10/56; 17.9%) and large deletions (19/56; 33.9%). Moreover, it was possible to detect HR in 1/8 (12.5%) embryos treated with RNA2X. These results report that the CRISPR/Cas9 system can be applied for site-specific edition of the bovine genome, which could have a great impact on the development of large animals resistant to important zoonotic diseases.

Purification of alpha-fetoprotein from human cord serum with demonstration of its antiestrogenic activity.

Alpha-fetoprotein (AFP) was purified from pooled human cord serum to determine whether it would be similar to purified mouse AFP in its ability to be transformed into an antiestrogen by incubation with estradiol (E2). Greater purity was attained with a three-step purification procedure of chromatofocusing, Blue-Sepharose chromatography and immunoaffinity chromatography than with a two-step procedure of polyacrylamide gel electrophoresis followed by Blue-Sepharose chromatography. Nevertheless, both procedures rendered AFP in a form that was transformable by E2 to an antiestrogen, although the product of the three-step procedure afforded more consistent biological activity. Removal of albumin from AFP was crucial for transformation of AFP to an antiestrogen. Thus, human AFP is similar to mouse AFP in being transformed to an antiestrogen upon incubation with E2, even though there is only 66% structural homology between the two proteins, and human AFP lacks the high-affinity binding site for E2 present in the mouse AFP molecule.

Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina.

PURPOSE: Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA-3 reactor in the province of Buenos Aires, Argentina. (l)-4p-dihydroxy-borylphenylalanine fructose complex (BPA-F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT. METHODS: Two kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA-3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario. RESULTS: Concentration-time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung-to-blood ratio of 1.3 ± 0.1 was observed from 80 min after the end of BPA-F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect quantification of the estimated value in the explanted healthy lung. The proposed preclinical animal model allowed for the study of the explanted lung. As expected, the boron concentration values fell as a result of the application of the preservation protocol required to preserve the lung function. The distribution of the boron concentration retention factor was obtained for healthy lung, with a mean value of 0.46 ± 0.14 consistent with that reported for metastatic colon carcinoma model in rat perfused lung. Considering the human lung model and suitable tumor control probability for lung cancer, a promising average fraction of controlled lesions higher than 85% was obtained even for a low tumor-to-normal boron concentration ratio of 2. CONCLUSIONS: This work reports for the first time data supporting the validity of the ovine model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Collectively, the results and analysis presented would strongly suggest that ex situ whole lung BNCT irradiation is a feasible and highly promising technique that could greatly contribute to the treatment of metastatic lung disease in those patients without extrapulmonary spread, increasing not only the expected overall survival but also the resulting quality of life.

Risk factors for postoperative morbidity.

OBJECTIVE: Analysis of outcomes after coronary artery bypass grafting has focused on risk factors for operative mortality. Nonfatal perioperative morbidity is far more costly and more common after operation. To identify the risk factors that lead to postoperative morbidity, we evaluated 938 patients undergoing coronary artery bypass grafting at Albany Medical Center Hospital during 1993. METHODS: Multivariate statistical analysis was performed on preoperative patient variables to identify risk factors for either serious postoperative morbidity or increased hospital length of stay. Variables were considered both individually and in combination. For example, age was considered individually or in combination with other variables, including parameters of blood volume (i.e., age divided by red blood cell volume or Age/RBCVOL). Similar multivariate analysis was performed to identify independent risk factors for hospital mortality. RESULTS: In order of decreasing importance, the following patient variables were significantly associated with increased length of stay by stepwise Cox regression analysis: Age/RBCVOL, history of congestive heart failure, hypertension, femoral-popliteal peripheral vascular disease, chronic obstructive lung disease, and renal dysfunction. The combination variable, Age/RBCVOL, was an important risk factor for both increased length of stay and serious postoperative morbidity. Variables that were significant independent predictors of increased mortality, such as preoperative shock, and redo operation, were not risk factors for either serious morbidity or increased length of stay. CONCLUSIONS: We conclude that risk factors for postoperative morbidity are different from those for postoperative mortality. These results suggest that older patients with preoperative anemia and low blood volume who also have other comorbidities (congestive heart failure, stroke, chronic obstructive pulmonary disease, or hypertension) are at increased risk for postoperative complications. This allows identification of a high-risk cohort of patients who are likely candidates for interventions to lessen postoperative morbidity.

Operative outcome and hospital cost.

INTRODUCTION: Because of concern about increasing health care costs, we undertook a study to find patient risk factors associated with increased hospital costs and to evaluate the relationship between increased cost and in-hospital mortality and serious morbidity. METHODS: More than 100 patient variables were screened in 1221 patients undergoing cardiac procedures. Simultaneously, patient hospital costs were computed from the cost-to-charge ratio. Univariate and multivariate statistics were used to explore the relationship between hospital cost and patient outcomes, including operative death, in-hospital morbidity, and length of stay. RESULTS: The greatest costs were for 31 patients who did not survive operation ($74,466, 95% confidence interval $27,102 to $198,025), greater than the costs for 120 patients who had serious, nonfatal morbidity ($60,335, 95% confidence interval $28,381 to $130,897, p = 0.02) and those for 1070 patients who survived operation without complication ($31,459, 95% confidence interval $21,944 to $49,849, p = 0.001). Breakdown of the components of hospital costs in fatalities and in cases with nonfatal complications revealed that the greatest contributions were in anesthesia and operating room costs. Significant (by stepwise linear regression analysis) independent risks for increased hospital cost were as follows (in order of decreasing importance): (1) preoperative congestive heart failure, (2) serum creatinine level greater than 2.5 mg/dl, (3) New York state predicted mortality risk, (4), type of operation (coronary artery bypass grafting, valve, valve plus coronary artery bypass grafting, or other), (5) preoperative hematocrit, (6) need for reoperative procedure, (7) operative priority, and (8) sex. These risks were different than those for in-hospitality death or increased length of stay. Hospital cost correlated with length of stay (r = 0.63, p < 0.001), but there were many outliers at the high end of the hospital cost spectrum. CONCLUSIONS: We conclude that operative death is the most costly outcome; length of stay is an unreliable indicator of hospital cost, especially at the high end of the cost spectrum; risks of increased hospital cost are different than those for perioperative mortality or increased length of stay; and ventricular dysfunction in elderly patients undergoing urgent operations for other than coronary disease is associated with increased cost. Certain patient factors, such as preoperative anemia and congestive heart failure, are amenable to preoperative intervention to reduce costs, and a high-risk patient profile can serve as a target for cost-reduction strategies.

Risk factors for early hospital readmission after cardiac operations.

OBJECTIVE: Early hospital readmissions after cardiac procedures are both costly and harmful to patients. We investigated the factors that predispose to readmission to develop strategies to minimize this problem. METHODS: As part of a prospective data collection, patients having cardiac procedures at our institution are routinely tracked for 30 days after their discharge from the hospital. We reviewed 2650 patients in our cardiac database who underwent operations over the past 5 years. We used univariate and multivariate statistical techniques to identify risks for readmission. RESULTS: Of 2574 discharged patients, 252 (9.8%) required readmission. The most common causes of readmission are cardiac (42%), pulmonary (19%), gastrointestinal (10%), extremity complications (6.7%; deep vein thrombophlebitis, peripheral arterial vascular disease, and saphenous vein harvest site problems), sternal wound problems (7.5%), and metabolic problems (4%). Of more than 70 variables studied, only 6 are significant multivariate predictors of readmission: female sex (P =.002); diabetes (P =.001); chronic lung problems (P =.011); increased distance between home and hospital (P >.001); preoperative atrial fibrillation (P =.002); and preoperative chronic renal insufficiency (P =.002). Type of operation, redo procedures, and other intraoperative and postoperative variables are not important multivariate predictors of readmission. Prolonged hospital length of stay for the initial procedure did not cause more frequent readmission. The costs of initial hospitalization (operating room costs combined with postoperative in-hospital costs) were not significantly increased in those patients who required readmission. CONCLUSIONS: The high-risk patient for readmission is a woman with diabetes, chronic lung disease, renal insufficiency, and preoperative atrial fibrillation who lives at a distance from the hospital. Readmission does not depend on periprocedural variables (eg, cardiopulmonary bypass time) or on postoperative complications. High procedural costs from the initial hospitalization do not predispose to readmission. These results suggest interventions that may reduce readmission.

Oropharyngeal dysphagia after cardiac operations.

BACKGROUND: As many as 15% of hospitalized patients have oropharyngeal dysphagia. The incidence and causes of postoperative oropharyngeal dysphagia (OD) in patients having cardiac operations are poorly documented and the best treatment is uncertain. We undertook a study to evaluate OD in patients having cardiac operations. METHODS: As part of a quality improvement project, all patients operated on in 1998 and 1999 were monitored for the signs or symptoms of OD. Patients with OD had diagnostic and therapeutic interventions to limit adverse outcomes. At the end of the 2-year evaluation period, patient risk factors, diagnoses, results of interventions, and outcomes were measured. RESULTS: Thirty-one out of 1,042, patients (3%) had OD. OD is more common in older patients (p < 0.0001) with diabetes (p = 0.02), renal insufficiency (p = 0.012), hyperlipidemia (p = 0.046), and preoperative congestive heart failure (p < 0.0001), and in those having noncoronary artery bypass procedures (p < 0.0001). One patient with OD died from respiratory arrest, presumably secondary to aspiration. Modified barium swallow (MBS) identified oral dysphagia in 2 patients, pharyngeal dysphagia in 7 patients, and both oral and pharyngeal dysphagia in 17 patients. One patient had a structural defect (cervical osteophyte) causing dysphagia and 4 patients had no identifiable cause of dysphagia on MBS. Postoperative neurologic complications are more common in patients with OD. Ten of 31 patients (32%) with OD had some new neurologic complication after operation compared with 36 of 1,011 (3.5%) who had a postoperative neurologic problem without OD. In 19 patients with OD no cause for swallowing difficulty was identified. Specifically, no metabolic, myopathic, or infectious abnormalities were identified in any patient with OD. Hospital charges were significantly increased in patients with OD ($69,320 versus $36,087, p < 0.0001). Therapy consisting of modification of eating behavior and swallowing technique and in some severe cases enteral or parenteral feeding was successful in all patients except 1, but 4 patients required more than 4 months of supportive care before return to oral feeding was possible. CONCLUSIONS: OD is associated with increased cost and morbidity. Older patients with diabetes, preoperative heart failure, and renal insufficiency are at increased risk for OD. Early recognition and intervention is likely to result in satisfactory outcome but may be associated with a protracted postoperative course.

Verapamil prophylaxis for postoperative atrial dysrhythmias: a prospective, randomized, double-blind study using drug level monitoring.

Orally administered verapamil hydrochloride (80 mg every 8 hours) or a placebo was given to 109 patients after coronary artery bypass grafting in a randomized, double-blind manner to test the efficacy of verapamil in preventing postoperative atrial dysrhythmias. The test drug was given through a nasogastric tube beginning 4 to 6 hours after operation until oral ingestion was possible. Serum levels of verapamil were measured at selected times after operation and when postoperative atrial dysrhythmias occurred. Postoperative atrial dysrhythmias occurred in 10 of the 53 verapamil-treated patients and in 20 of the 56 placebo-treated patients. Patients with verapamil drug levels higher than 150 ng/ml had fewer postoperative atrial dysrhythmias than those with lesser verapamil levels (p = .034) or than placebo-treated patients (p = .012). Only 2 of 31 patients with drug levels higher than 150 ng/ml experienced postoperative atrial dysrhythmias. Approximately 40% of verapamil-treated patients had drug levels lower than 150 ng/ml at 48 hours after operation. It is concluded that oral administration of verapamil prevents postoperative atrial dysrhythmias in a dose-dependent fashion.

Preoperative aspirin ingestion increases operative blood loss after coronary artery bypass grafting.

Thirty-four patients were entered into a non-blinded, randomized study to test the effect of preoperative aspirin ingestion on postoperative blood loss and transfusion requirements after coronary artery bypass grafting. Sixteen patients in the aspirin-treated group had significantly increased chest-tube blood loss 12 hours after operation (1,513 +/- 978 versus 916 +/- 482 ml; p = 0.038). In addition, aspirin users had significantly increased requirements for postoperative packed red blood cells (4.4 +/- 3.5 versus 1.8 +/- 1.3 units; p = 0.014), platelets (1.3 +/- 1.3 versus 0.2 +/- 0.4 six-donor units, p = 0.0049), and fresh-frozen plasma (3.6 +/- 5.0 versus 0.78 +/- 1.6 units; p = 0.042) transfusions. The only patients requiring reoperation for bleeding were in the aspirin-treated group (2 patients). Six patients were not entered into the randomized part of the study because of excessively prolonged post-aspirin bleeding times (greater than 10 minutes). This finding suggests that a subset of patients are particularly sensitive to aspirin and have significantly prolonged bleeding times after aspirin ingestion. We conclude that aspirin ingestion increases postoperative blood loss and transfusion requirements, and we recommend discontinuation of aspirin therapy before cardiac procedures.

Long-term angiographic results of coronary endarterectomy.

BACKGROUND: To evaluate the long-term patency of endarterectomized coronary vessels, we studied patients having recatheterization after coronary artery bypass grafting. METHODS: Forty-one clinical and angiographic variables were analyzed in 97 study patients who had coronary endarterectomy (CE) and in 154 control patients who did not have CE but who had repeat catheterization after coronary artery bypass grafting. RESULTS: Ninety-seven patients had 132 CEs. The right coronary artery was the most commonly endarterectomized vessel (73 of the 132 endarterectomized vessels). At a mean of 7.1 years of follow-up, significantly fewer bypass grafts to endarterectomized vessels were patent compared with nonendarterectomized vessels (40% of endarterectomized vessels compared with 58% of nonendarterectomized vessels in study patients and 65% in control patients, p = 0.0003). The only predictor of long-term CE graft patency is age-adjusted body surface area (p = 0.0068). Patency in grafts to nonendarterectomized vessels is diminished by hypertension (p = 0.046) and current cigarette use (p = 0.024) and improved by use of mammary artery grafting (p < 0.0001). CONCLUSIONS: These results show that long-term patency in bypass grafts to endarterectomized vessels is less common than in nonendarterectomized vessels and that this patency is related to larger body size. Patency in nonendarterectomized vessels is reduced by risks of arteriosclerosis. This suggests that CE should be used with caution in smaller patients and that aggressive control of risk factors for atherogenesis is particularly important in patients who have CE. On the basis of these results, we speculate that the extent of disease is advanced in patients who require CE.