Complication Rates Following Total Ankle Arthroplasty in Inpatient versus Outpatient Populations: A Systematic Review & Meta-Analysis.

Total ankle arthroplasty (TAA) is used as an alternative to ankle arthrodesis for adults with severe ankle arthritis. Numerous orthopedic centers have entered the healthcare market offering fast-tracked joint replacement protocols, meanwhile, TAA has been excluded from these joint centers, and is primarily performed in the inpatient setting. The purpose of this study is to examine short-term complications in the inpatient and outpatient settings following TAA using a systematic review and quantitative analysis. We considered all studies examining short-term complications following TAA performed in the inpatient versus outpatient setting occuring within 1 year of the index operation. We summarized data using a pooled relative risk and random effects model. A pooled sensitivity analysis was performed for studies with data on complication rates for inpatient or outpatient populations, which did not have a control group. The quality of included studies was assessed using the Cochrane risk of bias tool. Nine studies were included in the quantitative analysis, with 4 studies in the final meta-analysis. Subjects undergoing inpatient surgery experienced a 5-times higher risk of short-term complications compared to the outpatient group (risk ratio 5.27, 95% confidence interval 3.31, 8.42). Results did not change after sensitivity analysis (inpatient weighted mean complication rate: 9.62% vs outpatient weighted mean 5.02%, p value <.001). The overall level of evidence of included studies was level III, with a moderate to high risk of bias. Outpatient TAAs do not appear to pose excess complication risks compared to inpatient procedures, and may therefore be a reasonable addition to experienced centers that have established a fast-track outpatient total joint protocol.

Mechanisms, screening modalities and treatment options for individuals with non-alcoholic fatty liver disease and type 2 diabetes.

Non-alcoholic fatty liver disease (NAFLD) exists as a spectrum of disease ranging from excessive accumulation of fat within the liver (simple steatosis), inflammation (non-alcoholic steatohepatitis) through to fibrosis, cirrhosis and end-stage liver disease. There is also an increased risk of hepatocellular carcinoma. The principal risk factor for NAFLD is overweight or obesity, along with type 2 diabetes, and NAFLD itself is also a risk factor for incident type 2 diabetes. Overweight/obesity is synergistic with alcohol consumption in causing progressive and insidious liver damage. Recent consensus advocates a change in nomenclature from NAFLD to 'metabolic associated fatty liver disease' (MAFLD), reflective of the associated metabolic abnormalities (insulin resistance/type 2 diabetes and metabolic syndrome components). Additional extra-hepatic manifestations of NAFLD include cardiovascular disease, chronic kidney disease and certain cancers. Unlike other micro- and macrovascular complications of type 2 diabetes, systematic screening or surveillance protocols have not been widely adopted in routine diabetes care to assess for presence/severity of NAFLD. Various screening tools are available (non-invasive tests and biochemical indices) combined with imaging techniques (e.g. transient elastography) to detect steatosis and more importantly advanced fibrosis/cirrhosis to facilitate appropriate surveillance. Liver biopsy may be sometimes necessary. Treatment options for type 2 diabetes, including lifestyle interventions (dietary change and physical activity), glucose-lowering therapies and metabolic surgery, can modulate hepatic steatosis and to a lesser extent fibrosis. Awareness of the impact of liver disease on the choice of glucose-lowering medications in individuals with type 2 diabetes is also critical.

Radiographic Union Scoring Scale for Determining Consolidation Rates in the Calcaneus.

The reliable evaluation of osseous consolidation after hindfoot osteotomy can be difficult. Concomitant hindfoot osteotomies often dictate the advancement of weightbearing, and radiographs are the mainstay imaging tool owing to cost, efficiency, and radiation exposure. Understanding the radiographic parameters that can be used to reliably determine osseous healing is paramount. However, currently, no reliable or validated method is available to determine osseous healing of hindfoot osteotomies in irregular bones of the foot. The purpose of the present study was to develop a radiographic healing scoring system that would enhance the diagnostic healing assessment after elective calcaneal osteotomy. We adapted existing orthopedic scales validated for healing in the leg for application in the irregular bones of the foot. A total of 168 cases were evaluated by 6 blinded assessors to test the interrater reliability of subjective healing assessment compared with the proposed scoring system. The radiographs were classified by postoperative period: ≤4 weeks, 5 to 12 weeks, and >12 weeks. The proposed scale had high interrater reliability but was burdensome. Using a priori item reduction protocols, a limited 6-item scale further improved internal consistency and reduced the burden. The result was excellent interrater reliability (α = 0.98, standard deviation 0.02, 95% confidence interval 0.91 to 0.96) among all assessors when using the scoring scale compared with unacceptable reliability (α = 0.438) for subjective osteotomy healing. The reliability of our system appeared superior to that of subjective assessment of osseous healing alone, even in the absence of clinical correlates after osteotomy of the calcaneus.

Development of a Radiographic Union Score for Determining Osteotomy Union Rates in Long Bones of the Foot.

Determining the status of bone healing after osteotomy can be challenging and has implications ranging from clinical decision-making to standardization of research outcomes without the use of computed tomography. To date, no method has been validated for determining osseous healing of an osteotomy site of the long bones of the foot. The purpose of the present study was to develop a radiographic union scoring system that would enhance the diagnostic healing assessment. We adapted existing orthopedic scales that had been validated for healing in the leg for application in the long bones of the foot. One hundred cases were evaluated by 6 blinded assessors to test the inter- and intrarater reliability of the subjective healing assessment compared with the proposed scoring system. The radiographs were classified by postoperative period: ≤4, 5 to 12, and >12 weeks. The proposed scale had a high interrater reliability but was burdensome. Using a priori item reduction protocols, the scale was limited to the 5 items with the best internal consistency, which significantly reduced the burden. The result was excellent interrater reliability (α = 0.87) among all assessors compared with acceptable reliability (α = 0.66) for the subjective osteotomy healing assessment. The intrarater reliability during the subsequent retest phase demonstrated similar relationships, with low agreement (r = 0.38) for subjective healing. Each of the items included in the final scoring scale had moderate to good agreement across all assessors (r = 0.51 to 0.63). The reliability of this system appeared superior to the subjective assessment of osseous healing alone, even in the absence of clinical correlates after an osteotomy in the foot.

The Tayside insulin management course: an effective education programme in type 1 diabetes.

AIMS: The Tayside insulin management (TIM) course is an intensive insulin management programme for adults with type 1 diabetes. The aim was to assess its effectiveness. METHODS: Haemoglobin A1c (HbA1c) and body mass index (BMI) from individuals with type 1 diabetes were collected 3 months before, and 6 and 24 months after the programme. The programme involved a full day of education per week for 4 weeks in a row. Quality of life was assessed using the standardised Audit of Diabetes-Dependent Quality of Life (ADDQoL) questionnaire completed both before and 3 months after the course. Subjects were also asked to complete a pre- and postcourse questionnaire gathering information about aspects of their diabetes management. In addition, individual satisfaction with course content and delivery was recorded. RESULTS: Participants had a median reduction in haemoglobin A1c (HbA1c) of 4 mmol/mol (0.4%) after 6 months and 5 mmol/mol (0.5%) 2 years after the course (p < 0.001). Mean daily dose of short-acting insulin decreased from 31.5 (1.9) units to 27.3 (1.9, p < 0.001). There was no significant change in BMI. There was an improvement in all 18 domains of the ADDQoL questionnaire. There was a decrease in hypoglycaemia unawareness from 34.3 ± 47.8% of patients to 8.6 ± 28% (p < 0.001), and a decrease in self-reported lipohypertrophy from 27.8% to 11.1% (p = 0.001). There was a significant reduction in the mean number of diabetic ketoacidosis and severe hypoglycaemic episodes. The number of blood glucose checks changed from 2.8 ± 2.1 to 3.2 ± 1.1 (p = 0.058) per day. Participant satisfaction with all aspects of course content and delivery was high. CONCLUSIONS: TIM is an effective intensive education programme for patients with type 1 diabetes.

Pocket 4 of the HLA-DR(alpha,beta 1*0401) molecule is a major determinant of T cells recognition of peptide.

To investigate the functional roles of individual HLA-DR residues in T cell recognition, transfectants expressing wild-type or mutant DR(alpha,beta 1*0401) molecules with single amino acid substitutions at 14 polymorphic positions of the DR beta 1*0401 chain or 19 positions of the DR alpha chain were used as antigen-presenting cells for five T cell clones specific for the influenza hemagglutinin peptide, HA307-19. Of the six polymorphic positions in the DR beta floor that were examined, mutations at only two positions eliminated T cell recognition: positions 13 (four clones) and 28 (one clone). In contrast, individual mutations at DR beta positions 70, 71, 78, and 86 on the alpha helix eliminated recognition by each of the clones, and mutations at positions 74 and 67 eliminated recognition by four and two clones, respectively. Most of the DR alpha mutations had minimal or no effect on most of the clones, although one clone was very sensitive to changes in the DR alpha chain, with loss of recognition in response to 10 mutants. Mutants that abrogated recognition by all of the clones were assessed for peptide binding, and only the beta 86 mutation drastically decreased peptide binding. Single amino acid substitutions at polymorphic positions in the central part of the DR beta alpha helix disrupted T cell recognition much more frequently than substitutions in the floor, suggesting that DR beta residues on the alpha helix make relatively greater contributions than those in the floor to the ability of the DR(alpha,beta 1*0401) molecule to present HA307-19. The data indicate that DR beta residues 13, 70, 71, 74, and 78, which are located in pocket 4 of the peptide binding site in the crystal structure of the DR1 molecule, exert a major and disproportionate influence on the outcome of T cell recognition, compared with other polymorphic residues.

Amnion: The Ideal Scaffold for Treating Full-Thickness Wounds of the Lower Extremity.

Amnion and amniotic tissue has been studied for more than 100 years in the treatment of acute and chronic wounds. Recent studies have focused on the use of amnion tissue in the management of full-thickness diabetic wounds, particularly of the lower extremities. With new harvesting, processing, and distribution technologies, amnion is increasingly available in treating these wounds. Current data and research show increased healing potential and decreased healing times, pain, drainage, and infection in wounds treated with amnion products. There are a variety of amnion products with varying differences and purposes, requiring additional research and comparison trials.

Clinical Outcomes Following an Open Gastrocnemius Recession Combined With an Endoscopic Plantar Fasciotomy.

At present, there is a paucity of literature describing the clinical outcomes following a combined gastrocnemius recession and endoscopic plantar fasciotomy. The purpose of the present report is to describe our preliminary findings following a combined gastrocnemius recession and endoscopic plantar fasciotomy for the treatment of plantar fasciitis and gastrocnemius equinus recalcitrant to conservative therapy. Twenty-five consecutive ankles in 23 patients (age 51.2 ± 12.5 years, 4 men) met the inclusion and exclusion criteria. The average follow-up was 3.7 months. Compared across time, there were statistically significant improvements in pain, t(24) = 7.878, P < .001; dorsiflexion, t(24) = -6.125, P < .001; and eversion, t(23) = -3.610, P = .001. Plantar flexion and inversion remained similar across time ( P = .722 and P = .268, respectively). No statistically significant correlations were found between age and any of the postoperative outcome variables ( P ≥ .056) or body mass index and any of the postoperative outcome variables ( P ≥ .140). The authors believe that an isolated plantar fasciotomy alleviates symptoms in the majority of patients. When gastrocnemius equinus is also present, however, the authors advocate performing an open gastrocnemius recession as well. If the gastrocnemius pathology is not addressed, symptoms are likely to persist. The findings of the present report confirm the effectiveness of a combined gastrocnemius recession and endoscopic plantar fasciotomy to improve pain and range of motion. LEVELS OF EVIDENCE: Case series, Level IV: Retrospective.

Modeling of globular proteins. A distance-based data search procedure for the construction of insertion/deletion regions and Pro----non-Pro mutations.

A distance-based database search scheme is proposed for modeling Pro----in non-Pro and insertion/deletion regions of homologous globular proteins up to six residues in length. In the first step, geometric descriptors, the number of residues involved and target distances corresponding to the separation of C alpha atom positions adjacent to the "missing" segment, are chosen. In the second step, a database of high-resolution X-ray structures is scanned for segments with similar descriptors and selected segments are binned according to conformational type. In the third and fourth steps, the selected conformations are docked into the protein, and geometric and energetic criteria are used to determine their viability as segment models. The fifth step consists of an interaction scheme in which the geometric descriptors are redefined. This compensates for the use of a limited database and/or for the use of a poor original protein model adjacent to the missing segment. The procedure has been tested on Pro----non-Pro mutations in the homologous proteins penicillopepsin and endothiapepsin, and on the insertion/deletion regions of the homologs penicillopepsin and endothiapepsin, trypsin and gamma-chymotrypsin and hen and human lysozyme. The test cases represent a wide variety of secondary structural elements (helix, sheet, turn and coil) and insertion/deletion lengths (0 to 4 residues). It is shown that 79% of the test cases are accurately modeled (within 0.54 A root-mean-square (r.m.s.) deviation for main-chain atoms) using the proposed scheme. Failure of the scheme (main-chain atom r.m.s. deviations greater than 1.29 A) in 21% of the cases appears to be related to the presence of infrequently observed conformations or locally unique folds of the target proteins with respect to the database (18% of the test cases); the remaining 3% are unexplained. Geometric and energetic criteria are able to discriminate between trial conformations that correspond to the X-ray structures and those that are different in 97% of the conformations generated by the distance-weighted database search scheme. The scheme is shown to be relatively insensitive to uncertainty in the template co-ordinates, since the geometric descriptors were taken from the homologous protein (r.m.s. deviations in the position of descriptors range from 0.18 to 1.35 A for the accurately modeled test cases). It is demonstrated that the scheme can be used to correct local sequence misalignments.

Construction of side-chains in homology modelling. Application to the C-terminal lobe of rhizopuspepsin.

A detailed and rule-based side-chain modelling procedure for globular proteins is presented. It uses the conformational information contained in a homologous (template) structure as a starting point and includes recipes for atom placement and for checking and improving the atomic positions. The scheme does not rely on intuitive judgements or visual examination of the model during construction or refinement. It comprises four stages; the first three are relatively simple and the fourth is more complex. In the first stage, initial conformations for as many atoms as possible are transferred from the template structure based on the application of trends reported previously. Second, these trends are used to correct poor van der Waals overlaps. Third, the remaining side-chains atoms (those for which no information is contained in the template) are placed by evaluating their rigid rotation, van der Waals surfaces. The fourth stage consists of a hierarchial series of conformational checks. They involve the evaluation of individual residue energies in the absence and presence of the rest of the protein relative to statistical trends observed in the template structure, the comparison of hydrogen-bonding patterns and side-chain accessibilities in the model and template and brief energy minimization followed by an evaluation of the rigid rotation potential energy surfaces of each side-chain. The checks pinpoint "incorrectly" modelled side-chains, suggest conformational changes and provide a means for determining the portions of the model that are likely to be correct and those likely to be in error. The procedure developed in the paper is tested by modelling the side-chains of the C-terminal lobe of the aspartyl proteinase rhizopuspepsin, using the rhizopuspepsin backbone and the homologous protein, penicillopepsin, as a template for the side-chains. The resultant model was compared to the high-resolution X-ray structure of rhizopuspepsin. Using penicillopepsin data only (stage I), 58% of the chi 1 dihedrals and 44% of the chi 2 dihedrals were modelled correctly. Once poor van der Waals overlaps had been corrected and all of the atoms had been placed (stages II and III), 86% of the chi 1 dihedrals and 75% of the chi 2 dihedrals were correct. After the refinement had been completed (stage IV), 92% of the chi 1 dihedrals and 81% of the chi 2 dihedrals were correctly positioned.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of side-chain orientations in homologous proteins.

The side-chain conformations of topologically equivalent residues in seven pairs of proteins ranging in sequence homology from 16% to 60% are compared. Both identical and mutated residues are included. For proteins with greater than 40% homology, it is found that at least 80% of the side-chain orientations of identical residues and 75% or more of the mutated residues in each pair of proteins have matching gamma atom dihedral angles (+/- 40 degrees); the comparison is not based strictly on chi 1 angles. Further, if a match is obtained at the gamma position, there is a high probability of matching for the delta atom(s) of the side-chain. For proteins with less than 25% homology the percentages are somewhat lower. Trends observed for conservative substitutions are essentially the same as those noted for mutated residues in general. Side-chain accessibility does not affect the probability of matches of identical residues; however, less accessible pairs of mutated residues have 10 to 20% higher matching probabilities than do exposed residues. Mismatches can frequently be related to large B-factors, certain types of amino acid substitutions, or the appearance of multiple minima on the side-chain potential energy surfaces and are most likely to occur for certain small residues (Ser, Thr, Val). Analysis of all the results makes possible the formulation of a set of rules for side-chain positioning in the modeling of homologous proteins.

Healing in the new millennium: bone stimulators: an overview of where we've been and where we may be heading.

Electromagnetic fields and their uses in bone healing have been fairly well studied, with most results showing improvement in healing of both bone and cartilage. Most supportive data are found in relation to the spine, femur, and tibia, but there is increasing evidence for its use in the foot and ankle for treatment of nonunions and as an adjunctive device in arthrodeses, particularly in high-risk populations. There are varying data and a significant variety of quality in the current research and publications concerning the use of electrical bone stimulation in the treatment of the foot and ankle. Thus, there is a definite need for further investigation and high-quality study designs to determine the most effective treatment modalities and pathologies best used with bone stimulation. Bone stimulation should be viewed as an adjunctive procedure in which the surgeon optimizes the high-risk patient both medically or surgically whenever possible. But when used appropriately, bone stimulation has the potential to influence outcomes and aid in bone healing when complications arise and in high-risk populations.

A comparison of inpatient and outpatient ASCT.

Outpatient high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been shown to be feasible in terms of physical morbidity and mortality outcomes, but few data exist on the psychosocial impact of delivering such aggressive therapy in this manner. The purpose of this observational study was to compare effects of inpatient (n = 20) and outpatient (n = 21) modes of care on physical status, psychological well-being, quality of life, personal finances and caregiver burden. Most patients were treated according to their preference for inpatient or outpatient care. Those choosing outpatient care were screened for eligibility according to established criteria for ambulatory management. Measures were taken at baseline, then at days 4-6, 12-16 and 30 post ASCT. Results showed that overall, the psychological, physical, social and financial outcomes of the outpatient ASCT group were comparable, to or better than inpatients. Factors that seem to be important for successful outpatient management are previous experience with cancer treatment, a satisfying quality of life, physical well-being, patient's preference for a particular mode of care and physical proximity to the treatment centre. The study results suggest that outpatient ASCT is an efficient, effective and acceptable form of care for motivated patients and caregivers who have the physical and psychological capability and desire to receive cancer treatment in this manner.

Analysis of sperm chromosome complements before, during, and after chemotherapy.

Sperm chromosomal abnormalities were assessed in testicular cancer patients before, during, and after BEP (bleomycin, etoposide, cisplatin) chemotherapy (CT). Multicolor fluorescence in situ hybridization (FISH) analysis was employed to detect aneuploidy for chromosomes 1, 12, X, and Y, and diploidy. Sperm samples were cryopreserved and coded before analysis to facilitate "blind" analysis. Complete results at all time points was available for only one patient. A total of 60,400 sperm were analyzed: 20,004 before CT, 20,005 during CT, and 20,391 after CT. There was a significant increase in the frequency of 24,XY sperm during (0.33%) and post-CT (0.34%) compared to pre-CT (0.14%). This study suggests that there may be a significantly increased risk of chromosomal abnormalities in sperm of CT patients during and immediately post-CT, similar to that shown in animal models.

Fractures of the talus: a comprehensive review.

The talus, a highly specialized bone with a unique anatomic design, is crucial for normal ambulation. Although uncommon, talar fractures can be potentially devastating to the patient. Although all talar fractures require appropriate diagnosis and treatment, some require surgical skill for appropriate correction. This article reviews the literature on talar fractures and their treatments.

Overview of concepts and treatments in open fractures.

Open fractures are one of the few lower extremity surgical emergencies. These injuries require immediate treatment. If untreated, severe cases of open fracture can be limb threatening. This article is a review of the literature of open fractures and the current treatment guidelines.

Use of a model to understand prolactin and growth hormone specificities.

A human prolactin (hPRL) model based on a 2.1 A resolution X-ray refinement of porcine growth hormone is reported. Only regions clearly defined in the growth hormone template (the four-helix bundle) or previously assumed to be involved in hPRL-receptor binding (the bundle and the binding site loop) are included. A description of the model construction is provided and the resulting hPRL structure is used to interpret mutation/activity data for the cross-reactivity of human growth hormone (hGH) with the lactogenic receptor and the binding of human and bovine prolactin to the lactogenic receptor. The recognition of hPRL by its receptor unexpectedly appears to resemble more closely the interaction of hGH with the somatogenic receptor than with the lactogenic receptor. Each hGH binds to two receptor molecules, and an essential second messenger mediated by correct formation of the receptor-receptor interface has been proposed. The absence of receptor cross-reactivity for hPRL is linked to key sequence changes in hPRL which could disrupt hPRL-somatogenic receptor binding at the second site. A number of previous experiments have relied on the assumption that bioactivity is mediated by homologous residues at topologically equivalent positions. According to the model, this does not appear to be strictly true at either binding site. Good correlation at equivalent positions may be restricted to residues that are important for maintaining binding site shape as well as providing complementary stabilizing interactions between the hormone and receptor. Experiments are proposed to test our hypotheses.