Ceramic Total Knee Arthroplasty: Ready to Go?

Total knee arthroplasty (TKA) is a well-established surgical procedure in the late stages of knee osteoarthritis. Nevertheless, this procedure is associated with a percentage of unsatisfactory results and biomechanical failures, with aseptic loosening being the most common cause of revision. Beside these problems, cutaneous and systemic hypersensitivity reactions to metals have arisen as an increasing concern after joint arthroplasties, even if allergies against implant materials are still a quite rare and not well-known problem. Ceramic composites have been recently used in prosthetic components, showing minimum wear and excellent long-term results in total hip replacement, due to their high resistance to scratching and their better wettability with respect to cobalt-chromium alloy. Furthermore, the biologic response to debris generated from these bearings is less aggressive. Knee joint simulator tests and clinical results demonstrate promising results of TKAs with ceramic components that should led to benefit for the patients

Interleukin-6, interleukin-1β, and tumor necrosis factor α in menstrual effluents as biomarkers of chronic endometritis.

Objective: To assess the relationship between chronic endometritis (CE) and proin␣ammatory cytokine levels in menstrual ef␣uents and to develop a simple noninvasive test for screening CE. Design: Case-control study. Setting: Academic center. Patient(s): Sixty-four women referred to our center for infertility. Intervention(s): Of␣ce hysteroscopy; endometrial biopsy; collection of menstrual blood at subsequent cycle. Main Outcome Measure(s): Interleukin (IL) 6, IL-1b, and tumor necrosis factor (TNF) a concentrations in menstrual ef␣uents. Result(s): Thirty-sixoutof64infertilewomenhadhistologicallyprovenCE.Theremaining28womenwereincludedascontrols.IL-6, IL-1b, and TNF-a levels were markedly higher in menstrual ef␣uents of women with CE compared with control subjects. Receiver operating characteristic curve analysis revealed a good CE screening capacity for all of the cytokines. The combined evaluation of either IL-6/TNF-a or IL-6/IL-1b increased the diagnostic capacity of the test, which reached a 100% sensitivity and a negative predictive value of 100 when at least one cytokine was found to exceed its cutoff value; it also reached a 100% speci␣city and a positive predictive value of 100 in cases of positivity of both cytokines. Logistic regression analysis con␣rmed the IL-6/TNF-a– based model as a signi␣cant predictor of CE. Conclusion(s): Proin␣ammatorycytokinelevelsareincreasedinmenstrualef␣uentsofwomen with CE. A test dosing IL-6 and TNF-a seems to have a high screening capacity for CE. (Fertil Steril! 2014;101:242–7. !2014 by American Society for Reproductive Medicine.

Liver fibrosis score, physical frailty, and the risk of dementia in older adults: The Italian longitudinal study on aging

Introduction: Liver fibrosis increases progressively with aging and has been associated with poorer cognitive performance in middle-aged and older adults. We investigated the relationships between a non-invasive score for advanced liver fibrosis (non-alcoholic fatty liver disease [NAFLD] fibrosis score [NFS]) and dementia risk. We also assessed physical frailty, a common geriatric condition which is associated to dementia. We tested the joint effects of physical frailty and fibrosis on dementia incidence. Methods: A total of 1061 older adults (65 to 84 years), from the Italian Longitudinal Study on Aging, were prospectively evaluated for the risk of dementia in a period between 1992 and 2001. Liver fibrosis was defined according to the NFS. Physical frailty was assessed according to the Fried's criteria. Cox proportional hazards models were used to estimate the short- and long-term risk of overall dementia, associated to the NFS, testing the effect modifier of physical frailty status. Results: Older adults with only high NFS (F3-F4) did not exhibit a significant increased risk of overall dementia. Over 8 years of follow-up, frail older adults with high NFS had an increased risk of overall dementia (hazard ratio [HR]: 4.23; 95% confidence interval [CI]: 1.22 to 14.70, P = .023). Finally, physically frail older adults with low albumin serum levels (albumin < 4.3 g/dL) and with advanced liver fibrosis (F3-F4 NFS) compared to those with lower liver fibrosis score (F0-F2 NFS) were more likely to have a higher risk of overall dementia in a long term-period (HR: 16.42; 95% CI: 1.44 to 187.67, P = .024). Discussion: Advanced liver fibrosis (F3-F4 NFS) could be a long-term predictor for overall dementia in people with physical frailty. These findings should encourage a typical geriatric, multidisciplinary assessment which accounts also for the possible co-presence of frail condition in older adults with chronic liver disease and liver fibrosis

KRAS-regulated glutamine metabolism requires UCP2-mediated aspartate transport to support pancreatic cancer growth

The oncogenic KRAS mutation has a critical role in the initiation of human pancreatic ductal adenocarcinoma (PDAC) since it rewires glutamine metabolism to increase reduced nicotinamide adenine dinucleotide phosphate (NADPH) production, balancing cellular redox homeostasis with macromolecular synthesis1,2. Mitochondrial glutamine-derived aspartate must be transported into the cytosol to generate metabolic precursors for NADPH production2. The mitochondrial transporter responsible for this aspartate efflux has remained elusive. Here, we show that mitochondrial uncoupling protein 2 (UCP2) catalyses this transport and promotes tumour growth. UCP2-silenced KRASmut cell lines display decreased glutaminolysis, lower NADPH/NADP+ and glutathione/glutathione disulfide ratios and higher reactive oxygen species levels compared to wild-type counterparts. UCP2 silencing reduces glutaminolysis also in KRASWT PDAC cells but does not affect their redox homeostasis or proliferation rates. In vitro and in vivo, UCP2 silencing strongly suppresses KRASmut PDAC cell growth. Collectively, these results demonstrate that UCP2 plays a vital role in PDAC, since its aspartate transport activity connects the mitochondrial and cytosolic reactions necessary for KRASmut rewired glutamine metabolism2, and thus it should be considered a key metabolic target for the treatment of this refractory tumour

Individualized treatment of genotype 1 Naïve patients : an Italian multicenter field practice experience

Background: Triple therapy including Telaprevir or Boceprevir still represents in many European countries the standard of care for patients with Hepatitis C Virus genotype 1 infection. The number of patients who received this treatment resulted generally lower than expected. We investigated, among na\u131\ua8ve patients, number and characteristics of treatment candidates who were started on triple or dual therapy in comparison to those who were deferred. Patients and Methods: 621 na\u131\ua8ve treatment candidates were prospectively evaluated at each center. Factors associated with decision to defer or treat with dual or triple therapy were investigated by univariate and multivariate analyses. Rates of Sustained Virological Response and safety profile were analysed. Results: Of candidates to treatment, 33% did not received it. It was mostly due to high risk of Interferon-induced decompensation. Of 397 patients who were started on treatment, 266 (67%) received triple, 131 dual. Among patient receiving treatment, unfavorable IL28B, severe liver damage and higher albumin were independently associated with the physician decision to administer triple therapy. Sustained Virological Response after dual therapy was 66.4%, after triple 73.7% (p = 0.14). 142 patients received Telaprevir. The choice of Telaprevir-based therapy was associated with higher Body Mass Index and advanced liver disease. Sustained Virological Response rates were 71.1% after Telaprevir and 76.6% after Boceprevir. Conclusions: Individualizing treatment with available regimens allows to maximize Sustained Virological Response and to reduce the number of patients who remain untreated. High proportion of patients with severe liver damage urgently need Interferon free treatment

Long-term results of 32-mm alumina-on-alumina THA for avascular necrosis of the femoral head

BACKGROUND: Ceramic bearings in total hip arthroplasty (THA) have been introduced in clinical practice to minimize the problem of polyethylene particle-induced osteolysis. The aim of the study is to report the results of 68 consecutive alumina-on-alumina THAs done in 61 patients for avascular necrosis (AVN) of the femoral head. MATERIALS AND METHODS: In all implants a press-fit cup was used; it was combined with a 32-mm alumina head and with titanium-alloy stems. The mean age at surgery was 50 years. At an average follow-up of 13 years two hips have been revised, one for periprosthetic infection and one for excessive abduction of the cup. RESULTS: No revision for aseptic loosening is recorded; one anatomical cementless femoral stem had radiological evidence of definite aseptic loosening. No dislocations occurred, and no osteolysis was observed. CONCLUSIONS: The results support the application of alumina-alumina THA for long-lasting replacements

Usefulness of bronchoalveolar lavage in suspect COVID-19 repeatedly negative swab test and interstitial lung disease

The diagnosis of coronavirus disease 2019 (COVID-19) relies on nasopharyngeal swab, which shows a 20–30% risk of false negativity [1]. Bronchoalveolar lavage (BAL) is reported to be useful in patients with pulmonary interstitial infiltrates on high-resolution computed tomography (HRCT). We investigated the usefulness of BAL in symptomatic patients with positive HRCT and a repeatedly negative swab test (‘grey zone’)