Mid-term results of a stemless ceramic on polyethylene shoulder prosthesis - A prospective multicentre study.

INTRODUCTION: Early reports of stemless shoulder arthroplasty have shown promising clinical and radiological outcomes. The purpose of this study was to report on the mid-term results of an implant that utilises a ceramic humeral head. METHODS: A prospective, consecutive, multicentre study of stemless shoulder prosthesis with a minimum of four years of follow-up was conducted between August 2009 and May 2012. The adjusted Constant-Murley Score (CMS), revision rate and presence of radiolucent lines were recorded at intervals. RESULTS: A total of 207 patients were eligible for study inclusion; 62.8% were female and mean age was 64.8 years (range 30-86). Mean follow-up was 70.7 months (range 48-100), 73% underwent TSA and 27% hemiarthroplasty. The mean CMS improvement was 42.6 (p < 0.0001) at 48 months. Radiolucencies were present in 2.7% of humeral zones and 14% of glenoid zones at 48-month follow-up. The revision rate was 6.3% with rotator cuff failure (2.9%) the most common indication. CONCLUSIONS: Mid-term results demonstrate that the studied stemless implant with a ceramic humeral head had clinical and radiological outcomes that are comparable to other reported studies.

Reliability of stemless shoulder arthroplasty in rheumatoid arthritis: observation of early lysis around the humeral component.

PURPOSE: To evaluate whether stemless shoulder implants in rheumatoid arthritis (RA) patients provide comparable functional outcomes to patients with osteoarthritis or post-traumatic arthritis. In addition, the study assessed for differences in incidence of radiolucent lines or proximal humeral bone loss during radiographic follow-up. METHODS: Consecutive stemless shoulder arthroplasties performed in RA patients and a matched control group were retrospectively identified between February 2012 and 2018. Thirty-five patients were included in each group: 24 total shoulder arthroplasty (TSA) and 11 hemiarthroplasty (HA). Patients were evaluated annually using the Oxford Shoulder Score (OSS) and radiographically. RESULTS: The mean OSS significantly improved in all groups until 24 months. The mean improvement for RA TSA and HA patients at 24 months was 19.86 (95% CI 10.66-29.05, p = 0.0004) and 19.71 (95% CI 7.33-32.31, p = 0.0084), respectively. The mean improvement in the control TSA and HA patients at 24 months was 20.86 (95% CI 17-24.71, p = 0.0001) and 17.86 (95% CI 1.36-34.35, p = 0.0381), respectively. During the study period, two patients in the RA TSA group (8%), one patient in the control TSA group (4%) and one patient in the control HA group (9%) required revision. The proportion of progressive proximal humeral bone loss after TSA was 33% in the RA group and 13% in the control group. CONCLUSION: Stemless shoulder implants can provide significant improvement in functional scores in RA patients in the short term. However, early bone loss around the humeral implant is a concern and the authors recommend long-term clinical and radiological follow-up.

Revision shoulder arthroplasty for failed surface replacement hemiarthroplasty.

PURPOSE: The aim of this study was to assess the reasons of failure of shoulder surface replacement hemiarthroplasty (SRH) and to evaluate the outcome of revision surgery. METHOD: The study group included 25 patients (26 shoulders) with failed SRHs. The mean time to revision surgery was 3.6 years. Their functional outcome was evaluated using adjusted Constant-Murley score at mean follow-up of 5.2 years (range 2-16 years). RESULT: Most common cause of failure was glenoid erosion (42%) and progressive failure of rotator cuff (31%). Median adjusted Constant-Murley score at mean follow-up of 5.2 years was 51.6. Median adjusted Constant-Murley score in patients who had primary diagnosis of osteoarthritis and had revision performed to anatomic TSA (14 shoulders) was 85 (range 40-100) at mean follow-up of 5 years compared to 36.3 (range 20-66.3) in the remaining patients at 5.4 years, p = 0.00008. CONCLUSION: Revision surgery for failed SRH can be technically challenging with variable results. Most common mode of failure was glenoid erosion. Functional outcomes are better in those with revision performed to anatomic TSA.

Factors associated with villus atrophy in symptomatic coeliac disease patients on a gluten-free diet.

BACKGROUND: Duodenal injury persists in some coeliac disease patients despite gluten-free diet, and is associated with adverse outcomes. AIM: To determine the prevalence and clinical risk factors for persistent villus atrophy among symptomatic coeliac disease patients. METHODS: A nested cross-sectional analysis was performed on coeliac disease patients with self-reported moderate or severe symptoms while following a gluten-free diet, who underwent protocol-mandated duodenal biopsy upon enrolment in the CeliAction clinical trial. Demographic factors, symptom type, medication use, and serology were examined to determine predictors of persistent villus atrophy. RESULTS: Of 1345 symptomatic patients, 511 (38%, 95% CI, 35-41%) were found to have active coeliac disease with persistent villus atrophy, defined as average villus height to crypt depth ratio ≤2.0. On multivariable analysis, older age (OR, 5.1 for ≥70 vs. 18-29 years, 95% CI, 2.5-10.4) was a risk factor while longer duration on gluten-free diet was protective (OR, 0.37, 95% CI, 0.24-0.55 for 4-5.9 vs. 1-1.9 years). Villus atrophy was associated with use of proton-pump inhibitors (PPIs; OR, 1.6, 95% CI, 1.1-2.3), non-steroidal anti-inflammatory drugs (NSAIDs; OR, 1.64, 95% CI, 1.2-2.2), and selective serotonin reuptake inhibitors (SSRIs; OR, 1.74, 95% CI, 1.2-2.5). Symptoms were not associated with villus atrophy after adjusting for covariates. Conclusions A majority of symptomatic coeliac disease patients did not have active disease on follow-up histology. Symptoms were poorly predictive of persistent mucosal injury. The impact of NSAIDs, PPIs, and SSRIs on mucosal healing in coeliac disease warrants further study.

Lack of adherence to SHEA-IDSA treatment guidelines for Clostridium difficile infection is associated with increased mortality.

OBJECTIVES: The objective of this study was to determine our institution's compliance with 2010 Society for Healthcare Epidemiology of America and IDSA Clostridium difficile infection (CDI) treatment guidelines and their respective outcomes. METHODS: We collected clinical parameters, laboratory values, antibiotic therapy and clinical outcomes from the electronic medical records for all patients hospitalized at our institution with a diagnosis of CDI from December 2012 to November 2013. We specifically evaluated whether SHEA-IDSA treatment guidelines were followed and evaluated the associations between guideline adherence and severe outcomes including mortality. RESULTS: We identified 230 patients with CDI meeting inclusion criteria during the study period. Of these, 124 (54%) were appropriately treated, 46 (20%) were under-treated and 60 (26%) were over-treated. All-cause 90 day mortality was 17.4% overall; 43.5% in the under-treated group versus 12.9% in those appropriately treated (P < 0.0001) and 10.9% in those appropriately treated plus over-treated (P < 0.0001). Similarly, 90 day mortality attributed to CDI was 21.7% in those under-treated versus 8.9% in those appropriately treated (P = 0.03) and 8.2% in those either appropriately treated or over-treated (P = 0.015). Severe-complicated CDI occurred in 46 patients. In this subgroup, there was a non-significant trend towards increased mortality in under-treated patients (56.7%) compared with appropriately treated patients (37.5%, P = 0.35). Under-treatment was also associated with a higher rate of CDI-related ICU transfer (17.4% versus 4.8% in those appropriately treated, P = 0.023). CONCLUSIONS: Adherence to CDI treatment guidelines is associated with improved outcomes especially in those with severe disease. Increased emphasis on provision of appropriate, guideline-based CDI treatment appears warranted.

Creation of a model to predict survival in patients with refractory coeliac disease using a multinational registry.

BACKGROUND: Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. AIM: To create a prognostic model to estimate survival of patients with refractory coeliac disease. METHODS: We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. RESULTS: The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11-63 cases per centre). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during a 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38-3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22-6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61-0.85). A simple weighted three-factor risk score was created to estimate 5-year survival. CONCLUSIONS: Using data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up.

Factors governing long-term adherence to a gluten-free diet in adult patients with coeliac disease.

BACKGROUND: A strict gluten-free diet is the cornerstone of treatment for coeliac disease. Studies of gluten-free diet adherence have rarely used validated instruments. There is a paucity of data on long-term adherence to the gluten-free diet in the adult population. AIMS: To determine the long-term adherence to the gluten-free diet and potential associated factors in a large coeliac disease referral centre population. METHODS: We performed a mailed survey of adults with clinically, serologically and histologically confirmed coeliac disease diagnosed ≥5 years prior to survey. The previously validated Celiac Disease Adherence Test was used to determine adherence. Demographic, socio-economic and potentially associated factors were analysed with adherence as the outcome. RESULTS: The response rate was 50.1% of 709 surveyed, the mean time on a gluten-free diet 9.9 ± 6.4 years. Adequate adherence (celiac disease adherence test score <13) was found in 75.5% of respondents. A higher level of education was associated with adequate adherence (P = 0.002) even after controlling for household income (P = 0.0220). Perceptions of cost, effectiveness of the gluten-free diet, knowledge of the gluten-free diet and self-effectiveness at following the gluten-free diet correlated with adherence scores (P < 0.001). CONCLUSIONS: Long-term adherence to a gluten-free diet was adequate in >75% of respondents. Perceived cost remains a barrier to adherence. Perceptions of effectiveness of gluten-free diet as well as its knowledge, are potential areas for intervention.

Toxin-mediated paracellular transport of antitoxin antibodies facilitates protection against Clostridium difficile infection.

The exotoxins TcdA and TcdB are the major virulence factors of Clostridium difficile. Circulating neutralizing antitoxin antibodies are protective in C. difficile infection (CDI), as demonstrated, in part, by the protective effects of actoxumab and bezlotoxumab, which bind to and neutralize TcdA and TcdB, respectively. The question of how systemic IgG antibodies neutralize toxins in the gut lumen remains unresolved, although it has been suggested that the Fc receptor FcRn may be involved in active antibody transport across the gut epithelium. In this study, we demonstrated that genetic ablation of FcRn and excess irrelevant human IgG have no impact on actoxumab-bezlotoxumab-mediated protection in murine and hamster models of CDI, suggesting that Fc-dependent transport of antibodies across the gut wall is not required for efficacy. Tissue distribution studies in hamsters suggest, rather, that the transport of antibodies depends on toxin-induced damage to the gut lining. In an in vitro two-dimensional culture system that mimics the architecture of the intestinal mucosal epithelium, toxins on the apical side of epithelial cell monolayers are neutralized by basolateral antibodies, and antibody transport across the cell layer is dramatically increased upon addition of toxin to the apical side. Similar data were obtained with F(ab')2 fragments, which lack an Fc domain, consistent with FcRn-independent paracellular, rather than transcellular, transport of antibodies. Kinetic studies show that initial damage caused by apical toxin is required for efficient neutralization by basolateral antibodies. These data may represent a general mechanism of humoral response-mediated protection against enteric pathogens.

New drugs and strategies for management of Clostridium difficile colitis.

Approaches for management of Clostridium difficile infection continually evolve as research reveals shifts in epidemiology, microbial pathogenesis, disease severity states, and response to therapy. These new discoveries significantly impact diagnostic and therapeutic strategies, given the high morbidity associated with this common nosocomial infectious diarrhea. Critically ill patients are at an increased risk of developing diarrheal illness like C. difficile and succumbing to potentially fatal complications of this infection. Early diagnosis of severe disease state may improve patient outcomes. In this article, we review treatment strategies and new approaches for the management of C. difficile in critically ill patients.

Bioabsorbable fixation of scaphoid fractures and non-unions; analysis of early clinical outcomes.

The vast majority of devices used for internal fixation of the scaphoid are metallic. This two-center study aimed to report the results of scaphoid fixation using a cannulated, bioabsorbable device made from a hydroxyapatite and poly-L-lactide composite in 29 consecutive patients. Fixation was performed for seven acute fractures and twenty-two established non-unions. Union was achieved in 72.4% of patients. Six of the acute fractures and fifteen of the non-unions united successfully. Modified Mayo Wrist Score ranged between good to excellent in all patients who successfully united, whereas patients who failed to unite ranged between poor to excellent, with one poor and two moderate scores. No adverse biocompatibility reactions were seen. Two failures with broken screws were re-explored and one of these was thought to be due to screw mal-placement. The device used is an alternative to conventional metal implants and produces comparable union rates to metallic devices in the short term.

Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study.

BACKGROUND: Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. AIM: To evaluate the efficacy and tolerability of larazotide acetate during gluten challenge. METHODS: This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. RESULTS: No significant differences in LAMA ratios were observed between larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between larazotide acetate and placebo groups. CONCLUSIONS: Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.

Can we identify patients at high risk of recurrent Clostridium difficile infection?

Although most patients with Clostridium difficile infection (CDI) can be managed effectively with discontinuation of prescribed antibiotics and additional treatment with oral metronidazole or vancomycin, up to 25% experience disease recurrence, usually within 30 days of treatment. Failure to mount a systemic anti-toxin antibody response differentiates patients with CDI and recurrent CDI from symptomless carriers of toxinogenic C. difficile. The immunological senescence that accompanies ageing may lead to impaired immune responses to C. difficile and contribute to the significant association between advancing age and increased risk of CDI recurrence. Inadequate immunity may also explain why previous episodes of recurrence constitute a significant risk factor for further CDI recurrences. Other risk factors for recurrent CDI include concurrent use of antibiotics for non-C. difficile infections (which perpetuate the loss of colonization resistance), proton-pump inhibitors, and other gastric acid anti-secretory medications, prolonged hospitalization, and severe underlying illness (as reflected by a high Horn index score). Prominent risk factors have been examined to develop and validate a clinical prediction tool for recurrent CDI, with three factors (age >65 years, severe underlying disease (by the Horn index score), and continued use of antibiotics for non-CDI infections) being highly predictive of CDI recurrence. Such simple clinical prediction rules have the potential to identify patients at high risk of recurrent CDI, and can alert the treating physician to the need for prompt recognition, confirmatory diagnosis and treatment with regimens ideally designed to mitigate the risk of subsequent recurrences.

A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge.

OBJECTIVES: In patients with celiac disease, enteropathy is caused by the entry of gluten peptides into the lamina propria of the intestine, in which their immunogenicity is potentiated by tissue transglutaminase (tTG) and T-helper type 1-mediated immune responses are triggered. Tight junction disassembly and paracellular permeability are believed to have an important role in the transport of gluten peptides to the lamina propria. Larazotide acetate is a tight-junction regulator peptide that, in vitro, prevents the opening of intestinal epithelial tight junctions. The aim of this study was to evaluate the efficacy and tolerability of larazotide acetate in protecting against gluten-induced intestinal permeability and gastrointestinal symptom severity in patients with celiac disease. METHODS: In this dose-ranging, placebo-controlled study, 86 patients with celiac disease controlled through diet were randomly assigned to larazotide acetate (0.25, 1, 4, or 8 mg) or placebo three times per day with or without gluten challenge (2.4 g/day) for 14 days. The primary efficacy outcome was the urinary lactulose/mannitol (LAMA) fractional excretion ratio. Secondary endpoints included gastrointestinal symptom severity, quality-of-life measures, and antibodies to tTG. RESULTS: LAMA measurements were highly variable in the outpatient setting. The increase in LAMA ratio associated with the gluten challenge was not statistically significantly greater than the increase in the gluten-free control. Among patients receiving the gluten challenge, the difference in the LAMA ratios for the larazotide acetate and placebo groups was not statistically significant. However, larazotide acetate appeared to limit gluten-induced worsening of gastrointestinal symptom severity as measured by the Gastrointestinal Symptom Rating Scale at some lower doses but not at the higher dose. Symptoms worsened significantly in the gluten challenge-placebo arm compared with the placebo-placebo arm, suggesting that 2.4 g of gluten per day is sufficient to induce reproducible gluten toxicity. Larazotide acetate was generally well tolerated. No serious adverse events were observed. The most common adverse events were headache and urinary tract infection. CONCLUSIONS: LAMA variability in the outpatient setting precluded accurate assessment of the effect of larazotide acetate on intestinal permeability. However, some lower doses of larazotide acetate appeared to prevent the increase in gastrointestinal symptom severity induced by gluten challenge.

Body mass index and the risk of obesity in coeliac disease treated with the gluten-free diet.

BACKGROUND: Coeliac disease is increasingly diagnosed and weight changes are common after adoption of a gluten-free diet (GFD), however data on body mass index (BMI) changes are limited. AIM: To assess changes in BMI after diagnosis in a large coeliac population. METHODS: A total of 1018 patients with biopsy confirmed coeliac disease seen at our centre were studied retrospectively. Initial and follow-up BMIs were recorded, as was GFD adherence as assessed by an expert dietitian. RESULTS: A total of 679 patients with at least two recorded BMIs and GFD adherence data were included in the study. Mean follow-up was 39.5 months. Compared to regional population data, the coeliac cohort was significantly less likely to be overweight or obese (32% vs. 59%, P < 0.0001). Mean BMI increased significantly after GFD initiation (24.0 to 24.6; P < 0.001). 21.8% of patients with normal or high BMI at study entry increased their BMI by more than two points. CONCLUSIONS: Individuals with coeliac disease have lower BMI than the regional population at diagnosis. BMI increases on the GFD, especially in those that adhere closely to the GFD. On the GFD, 15.8% of patients move from a normal or low BMI class into an overweight BMI class, and 22% of patients overweight at diagnosis gain weight. These results indicate that weight maintenance counselling should be an integral part of coeliac dietary education.

Noncoeliac enteropathy: the differential diagnosis of villous atrophy in contemporary clinical practice.

BACKGROUND: Duodenal villous atrophy (DVA) is a key diagnostic finding in coeliac disease (CD). However, the differential diagnosis for this finding is broad. AIM: To identify conditions causing noncoeliac enteropathy (NCE) with villous atrophy and methods to differentiate between CD and NCE in clinical practice. METHODS: Through record review we identified patients with DVA due to conditions other than CD. Patient demographics, clinical features and relevant investigations were compared with CD patients. Rates of CD misdiagnosis, and response to treatments were recorded. RESULTS: Thirty cases of NCE were identified with ten different aetiologies. Unspecified immune-mediated enteropathy was the most common aetiology; affecting 10 patients. Gastrointestinal symptoms were more common in NCE than those in CD patients (P < 0.01). Twenty of the 24 NCE patients tested were HLA-DQ2/DQ8 negative. Twenty-six NCE patients were negative for IgA tissue transglutaminase (tTG) (P = 0.0001). Intraepithelial lymphocytosis was absent in 10 (33.3%) patients. Twenty-one NCE patients initially misdiagnosed with CD and one with gluten intolerance were prescribed a gluten free diet (GFD). Fifteen of 22 had repeat biopsy and none showed histological improvement. CONCLUSIONS: Although coeliac disease is the most common cause of DVA, noncoeliac enteropathy is not rare and may easily be mistaken for coeliac disease. Noncoeliac enteropathy is suggested by a normal initial tTG (87%), lack of intraepithelial lymphocytosis on biopsy, and lack of histological response to a gluten free diet. Subjective response to gluten free diet has poor predictive value for coeliac disease. Noncoeliac enteropathy can often be confirmed by negative HLA-DQ2/DQ8 testing and targeted investigations can ascertain a definitive aetiology in most cases.

In-vitro evaluation of a polyurethane compliant-layer glenoid for use in shoulder arthroplasty.

A polyurethane glenoid component has been designed and manufactured as part of a total shoulder arthroplasty (TSA) system based on compliant-layer (CL) technology. Compared with conventional TSA designs, this biomimetic approach offers reduced friction and wear and potentially improved longevity. In-vitro evaluation of the glenoid system has included loosening and stability tests, and wear measurement using a specially constructed wear simulator. The results obtained support the hypothesis that a CL glenoid design may provide improved resistance to dynamic loosening and rim erosion, and demonstrate superior wear performance over a standard ultra-high molecular weight polyethylene design. This study not only confirms the feasibility of a CL glenoid component but also highlights the potential to increase implant longevity, thereby allowing earlier surgical intervention before poor glenoid bone stock and soft tissue compromise the outcome of TSA.

Nutritional status and functional capacity of hospitalized elderly.

BACKGROUND: The nutritional status of the aging individual results from a complex interaction between personal and environmental factors. A disease influences and is influenced by the nutritional status and the functional capacity of the individual. We asses the relationship between nutritional status and indicators of functional capacity among recently hospitalized elderly in a general hospital. METHODS: A cross-sectional study was done with 240 elderly (women, n = 127 and men, n = 113) hospitalized in a hospital that provides care for the public and private healthcare systems. The nutritional status was classified by the MNA (Mini Nutritional Assessment) into: malnourished, risk of malnutrition and without malnutrition (adequate). The functional autonomy indicators were obtained by the self-reported Instrumental Activity of Daily Living (IADL) and Activity of Daily Living (ADL) questionnaire. The chi-square test was used to compare the proportions and the level of significance was 5%. RESULTS: Among the assessed elderly, 33.8% were classified as adequate regarding nutritional status; 37.1% were classified as being at risk of malnutrition and 29.1% were classified as malnourished. All the IADL and ADL variables assessed were significantly more deteriorated among the malnourished individuals. Among the ADL variables, eating partial (42.9%) or complete (12.9%) dependence was found in more than half of the malnourished elderly, in 13.4% of those at risk of malnutrition and in 2.5% of those without malnutrition. CONCLUSION: There is an interrelationship between the nutritional status of the elderly and reduced functional capacity.