Reducing periprosthetic joint infection: What really counts?

Periprosthetic joint infection (PJi) remains one of the most challenging complications after joint arthroplasty. Despite improvements in surgical techniques and in the use of antibiotic prophylaxis, it remains a major cause of implant failure and need for revision. PJi is associated with both human host-related and bacterial agentrelated factors that can interact in all the phases of the procedure (preoperative, intraoperative and postoperative). Prevention is the first strategy to implement in order to minimize this catastrophic complication. The present review focuses on the preoperative period, and on what to do once risk factors are fully understood and have been identified

Mason type II and III radial head fracture in patients older than 65: is there still a place for radial head resection?

Purpose: To evaluate the clinical outcomes of radial head excision for multifragmentary radial head fracture in patients over 65 years old. Methods: We retrospectively examined 30 patients over 65 years of age treated with radial head excision for comminuted radial head fractures. Patients were evaluated through clinical examinations, administrative questionnaires (DASH—Disabilities of the Arm, Shoulder and Hand; MEPS—Mayo Elbow Performance Score, VAS—Visual Analog Scale) and plain films. Results: The mean follow-up was 40 months (range 24–72 months); 27 out of 30 patients claimed to be satisfied. The mean DASH score was 13 (range 3–45.8) and mean MEPS was 79 (range 65–97). The radiographic evaluation showed 21 cases of elbow arthritis; only two of them complained about pain. Heterotopic ossification was evident in six cases with functional impairment in only one patient. Six patients with increased ulnar variance had clinical distal radio-ulnar joint instability. Discussion: Radial head excision has been considered a safe surgical procedure with satisfactory clinical outcomes. Development in biomechanical studies and prosthetic replacement of the radial head question the validity of radial head excision. In current literature, there are neither long-term follow-up studies on radial head prosthesis outcomes nor studies which consider elderly patient samples. Conclusion: Radial head resection remains a good option when a radial head fracture occurs in elderly patients, taking into account the influence of poor bone quality and comorbidities on the outcome. Radial head excision is not indicated in the presence of associated lesions, because of the risk of residual elbow instability; complications associated with advanced age must be considered and a strict follow-up granted

Modulation of aldose reductase activity by aldose hemiacetals

Glucose is considered as one of the main sources of cell damage related to aldose reductase (AR) action in hyperglycemic conditions and a worldwide effort is posed in searching for specific inhibitors of the enzyme. This AR substrate has often been reported as generating non-hyperbolic kinetics, mimicking a negative cooperative behavior. This feature was explained by the simultaneous action of two enzyme forms acting on the same substrate

RELATIONSHIP BETWEEN POLYMORPHISMS OF TAS2R38 BITTER TASTE RECEPTOR AND CHRONIC UPPER AIRWAY INFECTIONS

1Department of Neuroscience, ENT Section, “Federico II” University of Naples, Italy 2Department of Translational Medical Sciences, European Laboratory for Food Induced Diseases, Napoli, Italy The presence of taste receptors in extra-oral tissues may suggest additional roles apart from taste perception. Recently, an increasing number of reports demonstrated that the bitter taste G-protein coupled receptors family T2R, expressed in ciliated epithelial cells of the respiratory tract, are able to detect bacterial products and to stimulate innate immune defense against pathogens. Most microbial agents, secretes chemical signals known as quorum-sensing molecules that regulate the expression of genes involved in biofilm formation, virulence and other vital processes for microorganisms. Among the quorum-sensing molecules, the AHLs produced by P. aeruginosa, activate the receptor for bitter T2R38 expressed in ciliated epithelial cells of the respiratory tract, whereas mutants of P. aeruginosa lacking the AHL are not able to activate it. The activation of the receptor results in an increase of the Ca2+ flow and the ciliary beat frequency, as well as stimulating the production of NO which acts as a bactericide against the pathogen. The Caucasian population express three common polymorphisms (Pro49Ala, Ala262Val, Val296Ile) for TAS2R38 that lead to two major haplotypes PAV and AVI. The expression of either haplotype gives respectively 2 forms of receptors ̶ functional or non-functional ̶ i.e. unable to respond to specific agonists such phenylthiocarbamide and propylthiouracil (PROP). The two haplotypes PAV and AVI segregate into two major phenotypic classes: the "functional", sensitive to bitter, are homo- or heterozygous for the allele PAV, the "non-functional", are homozygous for the allele AVI. The genetic variations of the receptor TAS2R38 that affect sensitivity to bitter taste can help determine individual differences in susceptibility to bacterial infections of the respiratory tract allowing to plan a “target therapy”. Cellular cultures from homozygous PAV/PAV individuals showed a more effective NO production, mucociliary clearance and bactericide effect than cultures from AVI/PAV or AVI/AVI individuals. As a consequence it is reasonable to assume that patients with genotype AVI/PAV or AVI/AVI are at greater risk of contracting infections from gram-negative, compared with homozygous PAV. Some authors have studied the correlation between genotype and microbiological results TAS2R38 tissue of respiratory mucosa. The result of this analysis proved to be very interesting, because it showed a significant difference in the frequency of non-functional (AVI) than functional (PAV) among patients whose cultures were positive for Gram-negative bacteria, including P. aeruginosa. The aim of the study was to characterize phenotypically the sensitivity to PROP and the receptor polymorphisms of TAS2R38, in patients with chronic or recurrent infections of the upper respiratory tract to identify high risk patients. The identification of high-risk individuals would allow to draw up protocols for specific follow-up and appropriate “target therapy”

Head and Neck squamocellular carcinomas: E-cadherin and Keratin 5 as biomolecular markers

E- Cadherin is a transmembranar protein that plays an important role in the cellular adhesion and insure the connection of the tissue cells; it is present in the epithelial cells and its aberrant expression is correlated with different kinds of head and neck squamocellular carcinoma. Keratin 5 (K5) is present in the basal layer of a stratified squamous keratinized and non keratinized epithe-lium. The purpose of the present study was to identify the expression particularities of E-cadherin and Keratin 5 in rapport with the localization and the differentiation of various head and neck squamocellular carcinomas (larynx, pharynx, hard palate, tongue, submandibular, lip, gingival sulcus, nasal pyramid, maxillary, zygomatic). Immunoreactions for E-cadherin in the tumoral cells were examined according to the this score: 0 (0% positive cells), 1 (30%). The presence of maximum score (value 3) of E-cadherin was found in well-differentiated squamocellular carcinomas of laryngeal, tongue, lip, nasal pyramid, zygomatic area origin. A lower value of the score was present in the less differentiated histopathological type. The role of E-cadherin in the squamocellular carcinomas is far from being clarified. It seems that the trials to estimate a prognosis in this clinical entity should include a combination between the molecular markers, the histopathological data and clinical parameters. K5 expression was observed in all squamocellular carcinomas included in the present study with scores between 1 and 3. For well and moderately differentiated histopathological types, a maximum score of 3 was recorded for all of the cases, not including the laryngeal area, which presented a score of 2. The following scores were identified in the regions of the poorly differentiated carcinomas: Jaw, 3; gingival sulcus, 2; and tongue and submandibular area, 1. The present study confirms the role of K5 in the definition of the differentiation of squamocellular carcinoma of head and neck revealing a differential expression depending on the anatomic site of the primary tumor. These observations may aid with an improved stratification of head and neck squamocellular carcinoma, thus improving the diagnosis and treatment strategies for this type of cancer

non invasive methods for the assessment of hepatic fibrosis transient elastography hyaluronic acid 13c aminopyrine breath test and cytokeratin 18 fragment

Background. In the management of chronic hepatitis C (CHC) patients, liver biopsy is the gold standard for liver fibrosis assessment despite some technical limits and risks. Non-invasive approaches have been proposed as alternative methods to evaluate structural liver damage. Aim. To investigate the diagnostic accuracy of transient elastography, 13C-aminopyrine breath test ( 13 C-ABT), serum hyaluronic acid (HA) and cytokeratin 18 Asp396 fragment (CK-18) as non-invasive methods of liver fibrosis assessment ad their correlation to METAVIR score. Material and methods. In a cohort of 57 CHC patients, liver stiffness, cumulative percentage of administered dose of 13C-aminopyrine at 120 min, serum HA and serum CK-18 concentration were determined. Diagnostic accuracy in detecting significant fibrosis (F ≥ 2), severe fibrosis (F ≥ 3) and cirrhosis (F = 4) was assessed by the area under the receiver operating characteristic curve. Results. Liver fibrosis score showed a strong correlation with liver stiffness (r = 0.667; p < 0.0001) and a significant inverse correlation with 13C-ABT results (r = -0.418; p = 0.0012). A weaker correlation was found with CK18 (r = 0.329; p = 0.0126) and no correlation with HA. Areas under the curve of elastography, 13C-ABT, HA and CK18 were: 0.98, 0.75, 0.69, 0.64, respectively, for F ≥ 2; 0.97, 0.69, 0.80, 0.66, respectively, for F ≥ 3; 0.95, 0.64, 0.70, 0.56, respectively, for F = 4. Conclusion. Elastography has the best diagnostic accuracy for the assessment of the degree of liver fibrosis in CHC patients. Its application can provide an alternative useful tool for monitoring the disease evolution

IL28Bpolymorphism genotyping as predictor of rapid virologic response during interferon plus ribavirin treatment in hepatitis C virus genotype 1 patients

AIM: To clarify the association of interleukin-28B (IL28B) single nucleotide polymorphisms (SNPs) with hepatitis C virus (HCV) viremia changes for assessment of interferon (IFN) response. METHODS: A cohort of 118 Caucasian treatment-naïve HCV-G1 infected patients, treated with pegylated-IFN alpha 2a or 2b associated with ribavirin (53 responders, 65 non-responders) during the period 2010-2012, were genotyped for IL28B SNPs rs12979860 C>T and rs8099917 T>G. Genotyping was performed by real-time allelic discrimination assay. Serum HCV RNA levels were assayed at 2, 4, 12, 24 and 48 wk during therapy. Correlation between IL28B genotypes and serum HCV RNA kinetics was investigated. Multivariable logistic regression analysis was performed to identify predictors of null-response. RESULTS: Twenty-six out of 118 patients (22%) had no HCV RNA decline ≥ 1 log IU/mL at therapy week 4 (null-responders). IL28B genotype was rs8099917 (G*)/rs1297860(**) in 21/26 (80%) of null-responder patients. Using multivariate analysis, it was shown that the presence of the rs8099917 G allele was the best predictor of null-response (OR = 7.9, 95%CI: 1.99-31.18). The presence of at least one favorable genotype showed a positive predictive value of above 90% for HCV RNA reduction ≥ log at week 4. Analysis of the HCV RNA kinetics during 12 wk of therapy in patients with IL28B rs12979860 CT heterozygosis (n = 73), according to their rs8099917 status, showed that the viremia reduction was significantly different in patients carrying the rs8099917 G allele compared to those with favorable homozygosis. CONCLUSION: Our findings emphasize the association of the IL28B rs8099917 G allele with HCV. Genotyping for both IL28B SNPs is useful in clinical practice for thorough patient risk stratification based on IFN responsiveness