Prevalence and Impact of Unexpected Positive Intraoperative Cultures in Total Hip or Knee Revision Surgery.

BACKGROUND: Our aim was to evaluate the prevalence and impact of unexpected positive intraoperative cultures (UPICs) on the outcome of presumed aseptic total knee and hip revision surgery. METHODS: Data regarding patients who underwent elective total hip or knee revision surgery from January 2003 to July 2017 due to preoperatively presumed aseptic reasons was retrospectively reviewed. Partial revisions and patients who had follow-ups below 60 months were excluded from the study. In all surgeries, at least 3 intraoperative samples were taken for microbial culture. Failure was defined as the need for rerevision due to any cause at 5 years and/or the need for antibiotic suppressive therapy. Overall, 123 total hip and 431 total knee revisions were eligible for the study. All cases had at least a 5 years follow-up. RESULTS: There were 420 cases (75.8%) that had all cultures negative, 108 (19.5%) had a single UPIC, and 26 (4.7%) had either ≥2 UPICs for the same microorganism or 1 UPIC for a virulent microorganism. This latter group was not associated with a significantly higher failure rate (2 of 26, 7.7%) compared to those in the aseptic group (54 of 528, 10.2%). Revisions performed within the first 24 months after primary implantation had a higher 5-years rerevision rate (19.3 versus 8.4%, P = .01), mainly attributable to aseptic causes. CONCLUSIONS: Total hip and knee revisions with UPICs were not significantly associated with a higher rerevision risk at 5 years. Those revisions performed within the first 24 months after primary arthroplasty had a higher rate of any-cause failure.

Executive summary: Guidelines for the diagnosis and treatment of septic arthritis in adults and children, developed by the GEIO (SEIMC), SEIP and SECOT.

Infection of a native joint, commonly referred to as septic arthritis, is a medical emergency because of the risk of joint destruction and subsequent sequelae. Its diagnosis requires a high level of suspicion. These guidelines for the diagnosis and treatment of septic arthritis in children and adults are intended for use by any physician caring for patients with suspected or confirmed septic arthritis. They have been developed by a multidisciplinary panel with representatives from the Bone and Joint Infections Study Group (GEIO) belonging to the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Paediatric Infections (SEIP) and the Spanish Society of Orthopaedic Surgery and Traumatology (SECOT), and two rheumatologists. The recommendations are based on evidence derived from a systematic literature review and, failing that, on the opinion of the experts who prepared these guidelines. A detailed description of the background, methods, summary of evidence, the rationale supporting each recommendation, and gaps in knowledge can be found online in the complete document.

Implication of Different Tumor Biomarkers in Drug Resistance and Invasiveness in Primary and Metastatic Colorectal Cancer Cell Lines.

Protein expression profiles are directly related to the different properties of cells and are conditioned by the cellular niche. As an example, they are the cause of the characteristic cell plasticity, epithelium-mesenchymal transition (EMT), and drug resistance of cancer cells. This article characterizes ten biomarkers related to these features in three human colorectal cancer cell lines: SW-480, SW-620, and DLD-1, evaluated by flow cytometry; and in turn, resistance to oxaliplatin is studied through dose-response trials. The main biomarkers present in the three studied lines correspond to EpCAM, CD-133, and AC-133, with the latter two in low proportions in the DLD-1 line. The biomarker CD166 is present in greater amounts in SW-620 and DLD-1 compared to SW-480. Finally, DLD-1 shows high values of Trop2, which may explain the aggressiveness and resistance of these cells to oxaliplatin treatments, as EpCAM is also highly expressed. Exposure to oxaliplatin slows cell growth but also helps generate resistance to the treatment. In conclusion, the response of the cell lines is variable, due to their genetic variability, which will condition protein expression and cell growth. Further analyses in this area will provide important information for better understanding of patients' cellular response and how to prevent resistance.

African derived phytocompounds may interfere with SARS-CoV-2 RNA capping machinery via inhibition of 2'-O-ribose methyltransferase: An in silico perspective.

Despite the ongoing vaccination against the life-threatening COVID-19, there is need for viable therapeutic interventions. The S-adenosyl-l-Methionine (SAM) dependent 2-O'-ribose methyltransferase (2'-O-MTase) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a therapeutic target against COVID-19 infection. In a bid to profile bioactive principles from natural sources, a custom-made library of 226 phytochemicals from African medicinal plants with especially anti-malarial activity was screened for direct interactions with SARS-CoV-2 2'-O-MTase (S2RMT) using molecular docking and molecular dynamics (MD) simulations as well as binding free energies methods. Based on minimal binding energy lower than sinefungin (a reference methyl-transferase inhibitor) and binding mode analysis at the catalytic site of S2RMT, a list of 26 hit phytocompounds was defined. The interaction of these phytocompounds was compared with the 2'-O-MTase of SARS-CoV and MERS-CoV. Among these compounds, the lead phytocompounds (LPs) viz: mulberrofuran F, 24-methylene cycloartenol, ferulate, 3-benzoylhosloppone and 10-hydroxyusambarensine interacted strongly with the conserved KDKE tetrad within the substrate binding pocket of the 2'-O-MTase of the coronavirus strains which is critical for substrate binding. The thermodynamic parameters analyzed from the MD simulation trajectories of the LPs-S2RMT complexes presented an eminent structural stability and compactness. These LPs demonstrated favorable druggability and in silico ADMET properties over a diverse array of molecular computing descriptors. The LPs show promising prospects in the disruption of S2RMT capping machinery in silico. However, these LPs should be validated via in vitro and in vivo experimental models.

Immunomodulation of T Helper Cells by Tumor Microenvironment in Oral Cancer Is Associated With CCR8 Expression and Rapid Membrane Vitamin D Signaling Pathway.

The immune system plays a key role in the protective response against oral cancer; however, the tumor microenvironment (TME) impairs this anti-cancer response by modulating T helper (Th) responses and promoting an anti-inflammatory environment. Regulatory T cells (Tregs) and Th2 effector cells (Teff) are associated with poor prognosis in oral squamous cell carcinoma (OSCC). However, the main immunomodulatory mechanisms associated with the enrichment of these subsets in OSCC remain unknown. We characterized Th-like lineages in Tregs and Teff and evaluated immunomodulatory changes induced by the TME in OSCC. Our phenotypic data revealed a higher distribution of tumour-infiltrating CCR8+ and Th2-like Treg in OSCC compared with non-malignant samples, whereas the percentages of Th1 cells were reduced in cancer. We then analyzed the direct effect of the TME by exposing T cell subsets to cancer secretomes and observed the OSCC secretome induced CCR8 expression and reduced cytokine production from both subsets. Transcriptomic analysis showed that the co-culture with OSCC secretome induced several gene changes associated with the vitamin D (VitD) signaling pathway in T cells. In addition, proteomic analysis identified the presence of several proteins associated with prostaglandin E2 (PGE2) production by rapid membrane VitD signaling and a reduced presence of the VitD binding protein. Thus, we analyzed the effect of VitD and PGE2 and observed that VitD promotes a regulatory Th2-like response with CCR8 expression whilst PGE2 also modulated CCR8 but inhibited cytokine production in combination with VitD. Finally, we evaluated the presence of CCR8 ligand in OSCC and observed increased chemokine CCL18, which was also able to upregulate CCR8 in activated Th cells. Overall, our data showed the immunomodulatory changes induced by the TME involving CCR8 expression and regulatory Th2 phenotypes, which are associated with PGE2 mediated VitD signaling pathway and CCL18 expression in OSCC.

MRI prostate contouring is not impaired by the use of a radiotherapy image acquisition set-up. An intra- and inter-observer paired comparative analysis with diagnostic set-up images.

PURPOSE: The use of MRI for radiotherapy planning purposes is growing but image acquisition using radiotherapy set-ups has impaired image quality. Whether differences in image acquisition set-up could modify organ contouring has not been evaluated. Therefore, we aimed to evaluate differences in contouring between paired of image sets that were acquired in the same scanning session using different parameters. MATERIAL AND METHODS: Ten patients underwent RT treatment planning with MRI co-registration. MRI was carried out using two different set-ups during the same session, MRI radiotherapy set-ups and MRI diagnostic set-ups. Prostates and rectums were retrospectively contoured in both image sets by 5 radiation oncologists and 4 radiologists. Intra-observer analysis was carried out comparing organ volumes, the Dice coefficient and hausdorff distance values between two contouring rounds. Inter-observer analysis was carried out by comparing individual contours to a generated STAPLE consensus contour, which is considered the gold standard reference. RESULTS: No significant differences were observed between MRI acquisition set-ups. Significant differences were observed for the dice and hausdorff parameters, comparing individual contours to the STAPLE consensus contour, when analysing diagnostic images between rounds, although raw values were similar. CONCLUSION: Prostate and rectum contours did not differ significantly when using diagnostic or radiotherapy MRI acquisition set-ups.

Core Microbiota in Central Lung Cancer With Streptococcal Enrichment as a Possible Diagnostic Marker.

BACKGROUND: Dysbiosis in lung cancer has been underexplored. The aim of this study was to define the bacterial and fungal microbiota of the bronchi in central lung cancer and to compare it with that of the oral and intestinal compartments. METHODS: Twenty-five patients with central lung cancer and sixteen controls without antimicrobial intake during the previous month were recruited. Bacterial and fungal distribution was determined by massive sequencing of bronchial biopsies and saliva and faecal samples. Complex computational analysis was performed to define the core lung microbiota. RESULTS: Affected and contralateral bronchi of patients have almost identical microbiota dominated by Streptococcus, whereas Pseudomonas was the dominant genera in controls. Oral and pulmonary ecosystems were significantly more similar in patients, probably due to microaspirations. Streptococcal abundance in the bronchi differentiated patients from controls according to a ROC curve analysis (90.9% sensitivity, 83.3% specificity, AUC=0.897). The saliva of patients characteristically showed a greater abundance of Streptococcus, Rothia, Gemella and Lactobacillus. The mycobiome of controls (Candida) was significantly different from that of patients (Malassezia). Cancer patients' bronchial mycobiome was similar to their saliva, but different from their contralateral bronchi. CONCLUSIONS: The central lung cancer microbiome shows high levels of Streptococcus, and differs significantly in its composition from that of control subjects. Changes are not restricted to tumour tissue, and seem to be the consequence of microaspirations from the oral cavity. These findings could be useful in the screening and even diagnosis of this disease.

Laparoscopically assisted ilio-inguinal lymph node dissection versus inguinal lymph node dissection in melanoma.

AIM: Morbidity of open inguinal lymphadenectomy (OIL) is high. We use laparoscopy for pelvic time, preservation of the greater saphenous vein and transverse inguinal incisions (laparoscopically assisted ilio-inguinal lymphadenectomy, LIIL) to improve postoperative outcomes. PATIENTS & METHODS: Retrospective comparison of 14 patients who underwent LIIL and seven patients who underwent OIL. RESULTS: Fourteen LIIL compared with seven OIL showed a statistically significant reduction in morbidity (15.3 vs 75%) and hospital stay (7 vs 15.7 days). Pelvic lymph node involvement (27%) was not detected preoperatively. With a mean follow-up of 36.2 (range: 3-137) months, local recurrence rate was 58.3% in LIIL and 40% in OIL. Overall survival was significantly higher in OIL than in LIIL. CONCLUSION: Compared with OIL, LIIL reduced postoperative complications and hospital stay.

Core Microbiota in Central Lung Cancer With Streptococcal Enrichment as a Possible Diagnostic Marker.

BACKGROUND: Dysbiosis in lung cancer has been underexplored. The aim of this study was to define the bacterial and fungal microbiota of the bronchi in central lung cancer and to compare it with that of the oral and intestinal compartments. METHODS: Twenty-five patients with central lung cancer and sixteen controls without antimicrobial intake during the previous month were recruited. Bacterial and fungal distribution was determined by massive sequencing of bronchial biopsies and saliva and faecal samples. Complex computational analysis was performed to define the core lung microbiota. RESULTS: Affected and contralateral bronchi of patients have almost identical microbiota dominated by Streptococcus, whereas Pseudomonas was the dominant genera in controls. Oral and pulmonary ecosystems were significantly more similar in patients, probably due to microaspirations. Streptococcal abundance in the bronchi differentiated patients from controls according to a ROC curve analysis (90.9% sensitivity, 83.3% specificity, AUC=0.897). The saliva of patients characteristically showed a greater abundance of Streptococcus, Rothia, Gemella and Lactobacillus. The mycobiome of controls (Candida) was significantly different from that of patients (Malassezia). Cancer patients' bronchial mycobiome was similar to their saliva, but different from their contralateral bronchi. CONCLUSIONS: The central lung cancer microbiome shows high levels of Streptococcus, and differs significantly in its composition from that of control subjects. Changes are not restricted to tumour tissue, and seem to be the consequence of microaspirations from the oral cavity. These findings could be useful in the screening and even diagnosis of this disease.

Rare Site Hepatocellular Carcinoma Metastasis.

INTRODUCTION: Besides more common sites such as lung or peritoneum, hepatocellular carcinoma (HCC) can metastatize to rare sites. We report herein a new metastatic site of HCC: the nail-bed. We also review other recently reported rare site HCC metastases (RSHM). CASE REPORT: A 66-year-old woman with a 12-year history of resected-stage IA HCC who later presented lung, spleen and brain metastases treated with surgery, systemic therapies (sorafenib, sunitinib, capecitabine) and radiotherapy. The patient was referred to us because of a painful and rapidly evolving mass in the nail-bed of the left thumb. Biopsy confirmed nail-bed HCC metastasis, and the finger was amputated. The patient died few weeks later. CONCLUSION: This case was an opportunity for us to review RSHM. This type of metastasis seems to be an early event, in the context of advanced stage HCC with elevated protein induced by vitamin K absence-II (PIVKA II). The Lee nomogram is useful in detecting patients at high risk of developing RSHM. We would suggest insisting on systemic treatment in these metastatic patients although overall survival after RSHM diagnosis is poor.

Prosthetic joint infection by Bordetella holmesii: Case report and a review of the literature.

INTRODUCTION: Bordetella holmesii is a Gram-negative coccobacillus involved in different infections mostly described in case reports. Prosthetic joint infections in relation to this pathogen are rare. Here, we present the third case of B. holmesii in a patient without anatomical or functional spleen dysfunction. CASE REPORT: The patient was a 62-year-old female with a total knee prosthesis implanted in 1997 that required multiple replacements of the femoral component due to aseptic loosening in the past years. The patient was admitted to our hospital for an elective replacement surgery due to new radiological signs of loosening. B. holmesii was isolated from synovial fluid obtained during surgery. The identification was performed by matrix-assisted laser desorption ionization-time of flight mass spectrometry and confirmed by 16S rRNA gene amplification and sequencing. Antibiotic treatment was started but 14 days after surgery the patient presented pain and joint effusion. An arthrocentesis was performed and synovial fluid culture was positive again for B. holmesii. Surgical debridement including polyethylene replacement was performed and antibiotic treatment was continued for 3 months. After a 2-year follow-up period, the patient remained asymptomatic and physical examination showed normal function of the prosthesis. CONCLUSION: B. holmesii is an uncommon cause of bone and joint infections. This case indicates that this microorganism is a potential pathogen of prosthetic or native arthritis, and it should be considered when cultures are negative and in cases presenting torpid evolution.

Prevalence and Impact of Positive Intraoperative Cultures in Partial Hip or Knee Revision.

BACKGROUND: Our aim is to investigate the impact of unexpected positive cultures on the outcome of partial prosthetic revisions. METHODS: Data regarding patients who underwent a partial hip or knee revision from 2003 and 2012 with the preoperative diagnosis of aseptic loosening was retrospectively reviewed. The protocol of revision included at least 3 intraoperative cultures. Failure was defined as the need for re-revision due to aseptic or septic loosening at 5 years. RESULTS: A total of 99 hip and 46 knee partial revisions were included. All cases had at least 5 years of follow-up. Ninety-seven cases (66.9%) had all cultures negative, 35 (24.1%) a single positive culture and 13 (9.0%) ≥2 positive cultures for the same microorganism. The median time from primary arthroplasty to partial revision was significantly shorter for patients with ≥2 positive cultures (26 months) than in those with all cultures negative (48 months) or with a single positive culture (51 months). Partial revisions performed within the first 5 years of implantation had a higher 5-year re-revision rate. The presence of a single positive culture during the partial exchange was not associated with a higher re-revision rate (2 of 35, 5.7%) than in those with negative cultures (3 of 97, 3.1%). On the contrary, re-revision rate was significantly higher in cases with ≥2 positive cultures (3 of 13, 23.1%) than in those with negative cultures (P = .02). CONCLUSION: Partial revisions performed within the first 5 years from implantation and ≥2 intraoperative positive cultures were associated with a higher re-revision risk at 5 years.

Debridement, Antibiotics, and Implant Retention Is a Viable Treatment Option for Early Periprosthetic Joint Infection Presenting More Than 4 Weeks After Index Arthroplasty.

BACKGROUND: The success of debridement, antibiotics, and implant retention (DAIR) in early periprosthetic joint infection (PJI) largely depends on the presence of a mature biofilm. At what time point DAIR should be disrecommended is unknown. This multicenter study evaluated the outcome of DAIR in relation to the time after index arthroplasty. METHODS: We retrospectively evaluated PJIs occurring within 90 days after surgery and treated with DAIR. Patients with bacteremia, arthroscopic debridements, and a follow-up <1 year were excluded. Treatment failure was defined as (1) any further surgical procedure related to infection; (2) PJI-related death; or (3) use of long-term suppressive antibiotics. RESULTS: We included 769 patients. Treatment failure occurred in 294 patients (38%) and was similar between time intervals from index arthroplasty to DAIR: the failure rate for Week 1-2 was 42% (95/226), the rate for Week 3-4 was 38% (143/378), the rate for Week 5-6 was 29% (29/100), and the rate for Week 7-12 was 42% (27/65). An exchange of modular components was performed to a lesser extent in the early post-surgical course compared with the late course (41% vs 63%, respectively; P < .001). The causative microorganisms, comorbidities, and durations of symptoms were comparable between time intervals. CONCLUSIONS: DAIR is a viable option in patients with early PJI presenting more than 4 weeks after index surgery, as long as DAIR is performed within at least 1 week after the onset of symptoms and modular components can be exchanged.

Different femoral rotation with navigated flexion-gap balanced or measured resection in total knee arthroplasty does not lead to different clinical outcomes.

PURPOSE: Femoral rotation in total knee arthroplasty (TKA) is hypothesized to vary in the same knee depending on the method used to establish it. METHODS: Thirty-eight patients who underwent TKA surgery using a measured resection technique (RT) were compared with 40 patients who underwent a flexion-gap balancing technique with computer-assisted (for navigation) surgery (FB-CAS) to assess clinical and radiographic alignment differences at two years postoperatively. In 36 of the 40 patients in the FB-CAS group, both methods were used. Intraoperatively, the transepicondylar femoral rotation (TEFR) in reference to the transepicondylar axis was established as the rotation that balanced the flexion gap. Once the TEFR was obtained, an analogous rotation as measured by a posterior reference femoral rotation (PRFR) cutting guide was determined. RESULTS: Femoral component rotation determined by the TEFR and PRFR methods differed in each of the knees. The median TEFR was 0.08°±0.6° (range - 1.5°, 1.5°), and the median PRFR was 0.06°±2.8° (range - 6°, 5°). The mean difference in the rotational alignment between the TEFR and PRFR techniques was 0.01° ± 3.1°. The 95% limits of agreement between the mean differences in measurements were between 6.2° external rotation and - 6.1° internal rotation. At 2 years postoperatively, we found no differences in the radiographic or clinical American Knee Society score between the two groups. CONCLUSION: Rotation of the femoral component in TKA can vary in the same knee depending on the surgical method used to establish it. This variation in femoral rotation is sufficiently small enough to have no apparent effect on the 2-year clinical outcome score. LEVEL OF EVIDENCE: II.

An MRI comparative image evaluation under diagnostic and radiotherapy planning set-ups using a carbon fibre tabletop for pelvic radiotherapy.

PURPOSE: To quantitatively and qualitatively evaluate and compare MR images acquired from the usual diagnostic set-up with images acquired in a radiotherapy set-up. MATERIALS AND METHODS: MR images of a phantom and 18 prostate cancer patients imaging using the usual diagnostic set-up with a curved tabletop (DX-set-up) and using a radiotherapy set-up (RT-set-up) with a flat tabletop, were analysed retrospectively. Quantitative assessments were made by measuring signal-to-noise ratio (SNR) and contrast to noise ratio (CNR). Non-parametric tests were used. Qualitative assessments were made independently by three radiologists. Inter-rater reliability was measured as the percentage of agreement and Gwet's AC2 test. RESULTS: The use of the RT-set-up was linked to 19.3% SNR drop on the phantom image. Up to 24% SNR prostate drop was observed in patients' images. Up to 34% CNR drop was observed in patients' images. Although image quality of the RT-set-up was acceptable, all measured domains were worse than the corresponding DX-set-up. Additionally diagnostic images were linked to a better percentage of agreement among raters. CONCLUSIONS: SNR, CNR and image quality were significantly worse when using the RT-set-up than with the DX-set-up although Image quality in the RT-set-up was acceptable.

Predictors of severity in ischemic colitis: Usefulness of early ultrasonography.

PURPOSE: The main objective was to evaluate the usefulness of early ultrasonography for determining prognosis of patients with ischemic colitis. MATERIALS AND METHODS: We reviewed the histories of patients with diagnosis of ischemic colitis over a period of 11 years. Two hundred twenty nine patients with ischemic colitis were included. Demographic, clinical, laboratory and sonographic findings were retrospectively analyzed. Patients were divided into two groups according to the outcome: mild (those who improved with conservative treatment) or severe (those who died or required surgery), and the findings of each group were compared. In addition, we developed a predictive model of multivariate logistic regression analysis, and then it was validated in a different population of 58 consecutive patients with ischemic colitis. RESULTS: The mild ischemic colitis group consisted of 184 patients (age 74,7±8,8years), and the severe group of 45 patients (age 78,6±7,7years). More pancolitis (p=0.005), altered pericolic fat (p=0.032) and free fluid (p=0.013) was observed in the severe ischemic colitis group compared with the mild group. Severe ischemic group had lower wall thickness (p=0.020) and higher resistive index than mild group (p=0.025). Multivariate analysis identified as protective factors to severe ischemic colitis: pain (p=0.026), diarrhea (p=0.034), rectal bleeding (p=0.000), and hypertension (p=0.001). Altered pericolic fat (p=0.008) and pancolitis (p=0.017) were sonographic findings significantly related to severe ischemic colitis. Our model correctly classified 88.4% of the study patients and 89.6% of the population of 58 patients used in validation. CONCLUSIONS: Sonographic features with clinical findings can predict the outcome of ischemic colitis. Our predictive model could differentiate properly between patients with mild or severe ischemic colitis.

Hydrodynamic IL10 Gene Transfer in Human Colon: Results from an "EX VIVO" Study with Potential Clinical Application in Crohn's Disease.

BACKGROUND: The aim of this work is to evaluate the efficacy of hydrodynamic venous IL10 gene delivery to "ex vivo" human colon segments and to determine its potential interest in Crohn's disease treatment. METHODS: Twenty human colon segments were obtained from surgical resections. Hydrodynamic transfection through the main vein of the pedicle with 50 mL of hIL10 plasmid (20 µg/mL) solution was performed on 13 of them. Tissue sections were cultured and DNA, RNA, and protein copies were determined after 1, 2, and 4 days. Data obtained were compared with 6 nontransfected specimens. Finally, 1 specimen was injected with gold nanoparticles, and their distribution was examined under electron microscope. RESULTS: IL10 DNA levels were higher in treated tissues than in controls (P < 0.001), decreasing along time. The amount of hIL10 RNA was significantly increased in treated tissues when compared with controls (P = 0.001). The indexes of protein IL10 translation in treated groups were much higher (P < 0.001) than the basal production. The protein expression was higher in transfected tissue (10-50-fold, with respect to control tissue); this difference being established during the first hours and maintained during, at least, 4 days. With electron microscopy, we hardly observed large (15 nm) gold nanoparticles within the tissue, always in the submucosa. However, multiple small (4 nm) nanoparticles were observed within the cytoplasm of enterocytes in mucosa. CONCLUSIONS: Hydrodynamic procedure efficiently delivers the IL10 gene to the human colon, achieving levels of tissue protein expression high enough to mediate pharmacological effects with interest in controlling immune response in patients with Crohn's disease.

Withholding Preoperative Antibiotic Prophylaxis in Knee Prosthesis Revision: A Retrospective Analysis on Culture Results and Risk of Infection.

BACKGROUND: A significant amount of patients undergoing revision surgery of a prosthetic joint turn out to have an infection. Withholding preoperative antibiotic prophylaxis in these patients to optimize culture yield during revision surgery remains a matter of debate. The aim of our study was to determine (1) the rate of positive intraoperative cultures with or without preoperative antibiotic prophylaxis and (2) the incidence of a prosthetic joint infection (PJI) during the follow-up in the 2 groups. METHODS: Medical files of patients in whom preoperative antibiotic prophylaxis was withheld until culture samples were taken (2007-2010, n = 284) and in whom antibiotic prophylaxis was given during the induction of anesthesia (2010-2013, n = 141) were retrospectively reviewed. RESULTS: The percentage of ≥1 positive cultures was the same in the group without (26%) and with preoperative prophylaxis (27%; P value, .7). PJI was diagnosed during revision surgery according to the Musculoskeletal Infection Society criteria in 6.7% patients not receiving preoperative prophylaxis and in 7.0% receiving it (P value, .79). We found no important differences in the type of microorganisms that were isolated in both groups. During a 3-month follow-up, an early PJI developed in patients undergoing total revision surgery in 6.4% of the nonpreoperative prophylaxis group vs 1.6% in the preoperative prophylaxis group (P value, .1). CONCLUSION: Preoperative antibiotic prophylaxis does not reduce culture yield in patients undergoing knee revision surgery. Our data show a trend toward a higher PJI rate in the postoperative period of total revision surgery when preoperative prophylaxis is withheld.

Analysing the integration of MR images acquired in a non-radiotherapy treatment position into the radiotherapy workflow using deformable and rigid registration.

AIM: Our aim was to analyse the feasibility of integrating an MRI acquired in a non-radiotherapy set-up into the prostate cancer radiotherapy workflow. MATERIAL AND METHODS: The MRIs of 15 prostate cancer patients, acquired with a flat table-top (MRI-flat), and with a curved tabletop (MRI-curve) were analysed. MRIs were rigidly (RIR) and non-rigidly registered (DIR) with CT images. The prostate and rectum were contoured in each image set and translated to the CT, and IMRT plans were computed taking into account structural changes after RIR and DIR (P-flatRIR, P-curveRIR and P-curveDIR). In addition the P-curveDIR was overlaid with RIR structures. Spatial overlap parameters and dose-volume histogram metrics were generated. RESULTS: No significant differences were observed among P-flatRIR and P-curveRIR or P-flatRIR and P-curveDIR. Median gamma-values: P-curveRIR, 95.3%; P-curveDIR, 96%, translated-P-curveDIR, 95%. DVH metrics for translated-P-curveDIR were: Dmin, 64.5Gy; Dmean, 70.06Gy; V95%, 100%. No statistically significant differences were found in the dosimetric MRI-flatDIR values. CONCLUSIONS: The dosimetric reproduction of treatment position image following image registration of non-radiotherapy set-up images suggests that it is feasible to integrate these images into the radiotherapy workflow.

Measurements of Functional Responses in Human Primary Lung Cells as a Basis for Personalized Therapy for Cystic Fibrosis.

BACKGROUND: The best investigational drug to treat cystic fibrosis (CF) patients with the most common CF-causing mutation (F508del) is VX-809 (lumacaftor) which recently succeeded in Phase III clinical trial in combination with ivacaftor. This corrector rescues F508del-CFTR from its abnormal intracellular localization to the cell surface, a traffic defect shared by all Class II CFTR mutants. Our goal here is to test the efficacy of lumacaftor in other Class II mutants in primary human bronchial epithelial (HBE) cells derived from CF patients. METHODS: The effect of lumacaftor was investigated in primary HBE cells from non-CF and CF patients with F508del/F508del, A561E/A561E, N1303K/G542X, F508del/G542X and F508del/Y1092X genotypes by measurements of Forskolin plus Genistein-inducible equivalent short-circuit current (Ieq-SC-Fsk + Gen) in perfused open-circuit Ussing chambers. Efficacy of corrector C18 was also assessed on A561E/A561E and F508del/F508del cells. RESULTS: Our data indicate that A561E (when present in both alleles) responds positively to lumacaftor treatment at equivalent efficacy of F508del in primary HBE cells. Similarly, lumacaftor has a positive impact on Y1092X, but not on N1303K. Our data also show that cells with only one copy of F508del-CFTR respond less to VX-809. Moreover, there is great variability in lumacaftor responses among F508del-homozygous cells from different donors. Compound C18 failed to rescue A561E-CFTR but not in F508del-CFTR, thus plausibly it has a different mechanism of action distinct from lumacaftor. CONCLUSIONS: CF patients with A561E (and likely also those with Y1029X) can potentially benefit from lumacaftor. Moreover, the methodology used here exemplifies how ex vivo approaches may apply personalized therapies to CF and possibly other respiratory diseases.