Is wear debris responsible for failure in alumina-on-alumina implants?: Clinical, histological, and laboratory investigations of 30 revision cases with a median follow-up time of 8 years

Background and purpose Ceramic-on-ceramic articulation is an attractive alternative to metal-on-polyethylene (PE) bearings, but little is known about the in vivo effects induced by dissemination of alumina wear debris in the periprosthetic tissues. We hypothesized that wear debris is not the main factor responsible for loosening and failure of the implant but that mechanical problems caused by incorrect surgical technique, prosthetic design, or trauma, may cause instability of the implants and result in production of wear debris

How Do Metal Ion Levels Change over Time in Hip Resurfacing Patients? A Cohort Study

Metal-on-metal hip resurfacing (MOM-HR) is offered as an alternative to traditional hip arthroplasty for young, active adults with advanced osteoarthritis. Nevertheless, concerns remain regarding wear and corrosion of the bearing surfaces and the resulting increase in metal ion levels. We evaluated three cohorts of patients with Birmingham hip resurfacing (BHR) at an average follow-up of 2, 5, and 9 years. We asked whether there would be differences in ion levels between the cohorts and inside the gender. Nineteen patients were prospectively analyzed. The correlation with clinical-radiographic data was also performed. Chromium, cobalt, nickel, and molybdenum concentrations were measured by atomic absorption spectrophotometry. Chromium and cobalt levels demonstrated a tendency to decrease over time. Such tendency was present only in females. An inverse correlation between chromium, implant size, and Harris hip score was present at short term; it disappeared over time together with the decreased ion levels. The prospective analysis showed that, although metal ion levels remained fairly constant within each patient, there was a relatively large variation between subjects, so mean data in this scenario must be interpreted with caution. The chronic high exposure should be carefully considered during implant selection, particularly in young subjects, and a stricter monitoring is mandatory

Diets including Animal Food Are Associated with Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a clinical condition with a prevalence of up to 25% in Western countries. Typical GERD symptoms include heartburn and retrosternal regurgitation. Lifestyle modifications, including diet, are considered a first-line therapeutic approach. To evaluate the impact of life habits on GERD in this cross-sectional study, we used data collected through an online survey from 1146 participants. GERD was defined according to the Montreal Consensus. For all participants, clinical and lifestyle characteristics were recorded. Overall, 723 participants (63.1%) consumed a diet including animal food (non-vegans), and 423 participants (36.9%) were vegans. The prevalence of GERD was 11% (CI 95%, 9–14%) in non-vegans and 6% (CI 95%, 4–8%) in vegans. In the multivariate analysis, after adjusting for confounding factors, subjects on a non-vegan diet were associated with a two-fold increase in the prevalence of GERD compared to vegans (OR = 1.96, CI 95%, 1.22–3.17, p = 0.006). BMI and smoking habits were also significantly associated with GERD. This study shows that an animal food-based diet (meat, fish, poultry, dairy, and eggs) is associated with an increased risk of GERD compared to a vegan diet. These findings might inform the lifestyle management of patients with GERD-related symptoms

"Shock and kill" effects of class I-selective histone deacetylase inhibitors in combination with the glutathione synthesis inhibitor buthionine sulfoximine in cell line models for HIV-1 quiescence

Latently infected, resting memory CD4+ T cells and macrophages represent a major obstacle to the eradication of HIV-1. For this purpose, "shock and kill" strategies have been proposed (activation of HIV-1 followed by stimuli leading to cell death). Histone deacetylase inhibitors (HDACIs) induce HIV-1 activation from quiescence, yet class/isoform-selective HDACIs are needed to specifically target HIV-1 latency. We tested 32 small molecule HDACIs for their ability to induce HIV-1 activation in the ACH-2 and U1 cell line models. In general, potent activators of HIV-1 replication were found among non-class selective and class I-selective HDACIs. However, class I selectivity did not reduce the toxicity of most of the molecules for uninfected cells, which is a major concern for possible HDACI-based therapies. To overcome this problem, complementary strategies using lower HDACI concentrations have been explored. We added to class I HDACIs the glutathione-synthesis inhibitor buthionine sulfoximine (BSO), in an attempt to create an intracellular environment that would facilitate HIV-1 activation. The basis for this strategy was that HIV-1 replication decreases the intracellular levels of reduced glutathione, creating a pro-oxidant environment which in turn stimulates HIV-1 transcription. We found that BSO increased the ability of class I HDACIs to activate HIV-1. This interaction allowed the use of both types of drugs at concentrations that were non-toxic for uninfected cells, whereas the infected cell cultures succumbed more readily to the drug combination. These effects were associated with BSO-induced recruitment of HDACI-insensitive cells into the responding cell population, as shown in Jurkat cell models for HIV-1 quiescence. The results of the present study may contribute to the future design of class I HDACIs for treating HIV-1. Moreover, the combined effects of class I-selective HDACIs and the glutathione synthesis inhibitor BSO suggest the existence of an Achilles' heel that could be manipulated in order to facilitate the "kill" phase of experimental HIV-1 eradication strategies

Chronic constipation diagnosis and treatment evaluation: The "CHRO.CO.DI.T.E." study

Background: According to Rome criteria, chronic constipation (CC) includes functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C). Some patients do not meet these criteria (No Rome Constipation, NRC). The aim of the study was is to evaluate the various clinical presentation and management of FC, IBS-C and NRC in Italy. Methods: During a 2-month period, 52 Italian gastroenterologists recorded clinical data of FC, IBS-C and NRC patients, using Bristol scale, PAC-SYM and PAC-QoL questionnaires. In addition, gastroenterologists were also asked to record whether the patients were clinically assessed for CC for the first time or were in follow up. Diagnostic tests and prescribed therapies were also recorded. Results: Eight hundred seventy-eight consecutive CC patients (706 F) were enrolled (FC 62.5%, IBS-C 31.3%, NRC 6.2%). PAC-SYM and PAC-QoL scores were higher in IBS-C than in FC and NRC. 49.5% were at their first gastroenterological evaluation for CC. In 48.5% CC duration was longer than 10 years. A specialist consultation was requested in 31.6%, more frequently in IBS-C than in NRC. Digital rectal examination was performed in only 56.4%. Diagnostic tests were prescribed to 80.0%. Faecal calprotectin, thyroid tests, celiac serology, breath tests were more frequently suggested in IBS-C and anorectal manometry in FC. More than 90% had at least one treatment suggested on chronic constipation, most frequently dietary changes, macrogol and fibers. Antispasmodics and psychotherapy were more frequently prescribed in IBS-C, prucalopride and pelvic floor rehabilitation in FC. Conclusions: Patients with IBS-C reported more severe symptoms and worse quality of life than FC and NRC. Digital rectal examination was often not performed but at least one diagnostic test was prescribed to most patients. Colonoscopy and blood tests were the "first line" diagnostic tools. Macrogol was the most prescribed laxative, and prucalopride and pelvic floor rehabilitation represented a "second line" approach. Diagnostic tests and prescribed therapies increased by increasing CC severity

Biological effects of metal degradation in hip arthroplasties

Metals and metal alloys are the most used materials in orthopedic implants. The focus is on total hip arthroplasty (THA) that, though well tolerated, may be associated with local and remote adverse effects in the medium-long term. This review aims to summarize data on the biological consequences of the metal implant degradation that have been attributed predominantly to metal-on-metal (MoM) THA. Local responses to metals consist of a broad clinical spectrum ranging from small asymptomatic tissue lesions to severe destruction of bone and soft tissues, which are designated as metallosis, adverse reactions to metal debris (ARMD), aseptic lymphocytic vasculitis associated lesion (ALVAL), and pseudotumors. In addition, the dissemination of metal particles and ions throughout the body has been associated with systemic adverse effects, including organ toxicity, cancerogenesis, teratogenicity, and immunotoxicity. As proved by the multitude of studies in this field, metal degradation may increase safety issues associated with THA, especially with MoM hip systems. Data collection regarding local, systemic and long-term effects plays an essential role to better define any safety risks and to generate scientifically based recommendations

New couplings, old problems: Is there a role for ceramic-on-metal hip arthroplasty?

Ceramic-on-metal (CoM) total hip arthroplasty (THA) theoretically combines both the advantages of ceramic-on-ceramic (CoC) and metal-on-metal (MoM) bearings: negligible rupture risk of the liner with a limited ion release. As primary endpoint, we asked whether serum cobalt, chromium and molybdenum concentrations in 20 CoM-THA patients at an average of 3-years follow-up were higher than those measured in the pre-operative population and correlate with clinical/radiological parameters. As secondary endpoint, we wanted to verify whether ion levels in CoM-THA patients were different from those obtained in a similar cohort of 29 MoM-THA patients at the same average follow-up. Ion values were measured by atomic absorption spectrometry. Functional outcome was assessed with Harris Hip Score and UCLA scale. Presence of radiographic radiolucencies around the implant, and acetabular inclination angle were evaluated. Chromium and cobalt levels in CoM-THA patients were significantly higher (p < 0.001) at 3-years follow-up than before surgery. Molybdenum concentrations were not significantly different (p = 0.45). No signs of implant loosening were recorded. Functional outcome was excellent with HHS and UCLA scale rising from 50 and 3.6 pre-operatively to 90.8 and 6.3, respectively at 3-years follow-up (p < 0.001). Chromium serum levels were significantly lower in CoM-THA than in MoM-THA group (p = 0.02) while cobalt values, even if lower, did not reach statistically significance (p = 0.054). Our results show that CoM-THA patients achieve excellent clinical outcome with a limited chromium release at 3-years follow-up

Effect of acetabular cup design on metal ion release in two designs of metal-on-metal hip resurfacing

The purpose of this observational prospective cohort study was to evaluate the serum concentrations of cobalt (Co), chromium (Cr), and nickel (Ni) at a 2-year followup in patients operated on with a novel design of hip resurfacing: Romax resurfacing system (RRS). RRS is characterized by the presence of an acetabular notch which theoretically provides a wider range of motion and a reduced incidence of groin pain. The presence of radiolucencies and functional outcome, assessed using the Harris hip score (HHS) and the University of California Activity scale (UCLA), were secondary endpoints. Moreover, these results were compared with those obtained in our previous study from a similar cohort of patients implanted using the Birmingham Hip Resurfacing (BHR) system. At a 2-year follow-up, the serum levels of Co in patients operated on using the RRS were five times higher (p50.0002) than those found before surgery (Co, means: 1.04 and 0.20 ng/mL, respectively); similarly, Cr levels were 13 times higher (p<0.0001) at a 2-year follow-up than before surgery (Cr, means: 1.69 and 0.13 ng/mL, respectively). Ni concentrations (0.42 and 0.78 ng/mL) were not significantly different (p50.16), even if they increased 86% after surgery. In the RRS patients, an inverse correlation was found between Co and Cr concentrations and length of follow-up (Co: r520.64, p50.0096; Cr: r5 20.45, p50.08). The serum levels of Co and Cr were not significantly different between RRS (Co: 1.04 ng/mL and Cr: 1.69 ng/mL) and BHR (Co: 1.39 ng/mL and Cr: 2.30 ng/mL) patients at 2 years (p50.95 and 0.26 for Co and Cr, respectively). Our results showed that RRS patients achieved an excellent clinical outcome with limited metal ion release