Mortality Due to Acute Respiratory Distress Syndrome in Latin America.

OBJECTIVES: Mortality due to acute respiratory distress syndrome (ARDS) is a major global health problem. Knowledge of epidemiological data on ARDS is crucial to design management, treatment strategies, and optimize resources. There is ample data regarding mortality of ARDS from high-income countries; in this review, we evaluated mortality due to ARDS in Latin America. DATA SOURCES: We searched in PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Latin American and Caribbean Health Science Literature databases from 1967 to March 2023. STUDY SELECTION: We searched prospective or retrospective observational studies and randomized controlled trials conducted in Latin American countries reporting ARDS mortality. DATA EXTRACTION: Three pairs of independent reviewers checked all studies for eligibility based on their titles and abstracts. We performed meta-analysis of proportions using a random-effects model. We performed sensitivity analyses including studies with low risk of bias and with diagnosis using the Berlin definition. Subgroup analysis comparing different study designs, time of publication (up to 2000 and from 2001 to present), and studies in which the diagnosis of ARDS was made using Pa o2 /F io2 less than or equal to 200 and regional variations. Subsequently, we performed meta-regression analyses. Finally, we graded the certainty of the evidence (Grading of Recommendations Assessment, Development, and Evaluation). DATA SYNTHESIS: Of 3315 articles identified, 32 were included (3627 patients). Mortality was 52% in the pooled group (low certainty of evidence). In the sensitivity analysis (according to the Berlin definition), mortality was 46% (moderate certainty of evidence). In the subgroup analysis mortality was 53% (randomized controlled trials), 51% (observational studies), 66% (studies published up to 2000), 50% (studies after 2000), 44% (studies with Pa o2 /F io2 ≤ 200), 56% (studies from Argentina/Brazil), and 40% (others countries). No variables were associated with mortality in the meta-regression. CONCLUSIONS: ARDS mortality in Latin America remains high, as in other regions. These results should constitute the basis for action planning to improve the prognosis of patients with ARDS (PROSPERO [CRD42022354035]).

Comparable bone penetration between antibiotic-loaded and plain bone cement in total knee arthroplasty.

INTRODUCTION: One of the main concerns around the use of antibiotic-loaded bone cement (ALBC) is the potential reduction in the mechanical properties of the cement when antibiotics are admixed. The purpose of this study was to determine whether there is a difference between plain cement and ALBC in terms of radiological intrusion into the bone in total knee arthroplasties (TKAs). METHODS: Prospective randomized study of 80 consecutive patients who underwent TKA. Depending on the cement used, patients were divided into two groups by a computer-generated randomization programme: the cement without antibiotic (Group 1) or the ALBC (Group 2). Cement intrusion was measured in postoperative radiographs in eight different regions in the tibial component and six regions in the femoral component. RESULTS: The average cement intrusion was similar in both groups (p = nonsignificance [n.s.]). Group 1 (plain cement) had an average cement intrusion in the femur of 1.4 mm (±0.4) and 2.4 mm (±0.4) in the tibia. In Group 2 (ALBC), the average cement intrusion in the femur came to 1.6 (±0.5) and 2.4 mm (±0.5) in the tibia. In 80% of the patients, the cement intrusion in the tibia averaged a minimum of 2 mm, being similar in both groups (p = n.s.). CONCLUSION: There are no differences in bone intrusion when comparing plain cement to ALBC. Therefore, the use of ALBC in primary TKA may be indicated, achieving optimal bone penetration. LEVEL OF EVIDENCE: Level I.

The Use of Erythromycin and Colistin Cement in Total Knee Arthroplasty Does Not Reduce the Incidence of Infection: A Randomized Study in 2,893 Knees With a 9-year Average Follow-Up.

BACKGROUND: One of the most severe complications of primary total knee arthroplasty (TKA) is prosthetic joint infection. Currently, the use of antibiotic-loaded cement for the prevention of infection is still controversial. The aim of the present study was to evaluate if the use of antibiotic-loaded cement reduces the infection rate in primary TKA in long-term follow-up (more than 5 years average follow-up). METHODS: This study is the follow-up extension of a prospective randomized study, with 2,893 cemented TKA performed between 2005 and 2010 at our institution. There were 2 different cohorts depending on which bone cement was used: without antibiotics (control group) or those loaded with erythromycin and colistin (study group). All patients received the same systemic prophylactic antibiotics. The patients were followed for a minimum of twelve months. The diagnosis of prosthetic joint infection was done according to Zimmerli criteria. RESULTS: In 1,452 patients, the prosthetic components were fixed using bone cement without antibiotics, whereas in 1,441 patients, bone cement was loaded with erythromycin and colistin. Both groups were comparable in terms of all the possible risk factors studied. We found a total of 53 deep infections, with a mean rate of 1.8%. There were no differences between the groups as to whether bone cement with or without antibiotics had been used (P = .58). The average duration of follow-up was 8.7 years. In terms of prosthetic revision due to aseptic loosening, there were no differences between groups (P = .32), with 33 revision arthroplasties in the control group and 37 in the study group. Moreover, we analyzed the erythromycin resistance rate, with no differences between both groups (P = .6). CONCLUSIONS: The use of erythromycin and colistin-loaded bone cement in TKA did not lead to a decrease in the rate of infection in long-term follow-up, a finding that suggests that its use would not be indicated in the general population.

Evaluation of a high resolution diode array for CyberKnife quality assurance.

PURPOSE: The CyberKnife quality assurance (QA) program relies mainly on the use of radiochromic film (RCF). We aimed at evaluating high-resolution arrays of detectors as an alternative to films for CyberKnife machine QA. METHODS: This study will test the SRS Mapcheck (Sun Nuclear, Melbourne, Florida, USA) diode array and its own software, which allows three tests of the CyberKnife QA program to be performed. The first one is a geometrical accuracy test based on the delivery of two orthogonal beams (Automated Quality Assurance, AQA). Besides comparing the constancy and repeatability of both methods, known errors will be introduced to check their sensitivity. The second checks the constancy of the iris collimator field sizes (Iris QA). Changes in the field sizes will be introduced to study the array sensitivity. The last test checks the correct positioning of the multileaf collimator (MLC). It will be tested introducing known systematic displacements to whole banks and to single leaves. RESULTS: The results of the RCF and diode array were equivalent (maximum differences of 0.18 ± 0.14 mm) for the AQA test, showing the array a higher reproducibility. When known errors were introduced, both methods behaved linearly with similar slopes. Regarding Iris QA, the array measurements are highly linear when changes in the field sizes are introduced. Linear regressions show slopes of 0.96-1.17 with r2 above 0.99 in all field sizes. Diode array seems to detect changes of 0.1 mm. In MLC QA, systematic errors of the whole bank of leaves were not detected by the array, while single leaf errors were detected. CONCLUSIONS: The diode array is sensitive and accurate in the AQA and Iris QA tests, which give us the possibility of substituting RCF with a diode array. QA would be performed faster than using the film procedure, obtaining reliable results. Regarding the MLC QA, the inability to detect systematic displacements make it difficult to confidently use the detector.

The use of a thin guide-wire for urethral definition in prostate SBRT treatments with Cyberknife.

PURPOSE: To study and analyze the effect of the use of a thin guide-wire instead of a Foley catheter for urethral definition in prostate stereotactic body radiation therapy (SBRT) treatments and to compare treatment parameters in both situations. MATERIAL AND METHODS: Thirty-seven prostate SBRT patients were employed in this study. A Foley catheter was employed in nine of them, and a guide-wire was employed in the other 28 patients. For each of the 28 patients in which the guide-wire was employed, a comparison between urethral positions in both situations was performed, allowing for a margin definition of the urethra when a Foley catheter was employed. Displacements of the prostate during treatment were obtained, allowing for an analysis of prostate positions in both situations. Also, different treatment parameters such as the number of treatment interruptions, couch movements performed, and x-rays needed were gathered. RESULTS: Large differences between urethral positions can be found in the anterior-posterior (AP) directions compared to those in the lateral (LAT) direction. Differences are also larger in areas closer to the base of the prostate, where margins applied in the case of using a Foley catheter are 16 mm with a mean displacement of 6 mm in the posterior direction. No differences in the treatment parameters were found during treatment in both situations. The difference found in absolute prostate pitch rotations suggests that the Foley catheter provokes a shift of the prostate position, which does not occur when employing the guide-wire. CONCLUSIONS: Foley catheters shift the urethral position, making them a wrong surrogate of the urethra when no catheters are present. The margins needed to assess uncertainties introduced by the use of a Foley catheter are larger than those usually applied. The use of a Foley catheter did not present any additional difficulty during treatment delivery in terms of images employed or interruptions produced.

ESSKA and EBJIS recommendations for the management of infections after anterior cruciate ligament reconstruction (ACL-R): prevention, surgical treatment and rehabilitation.

PURPOSE: Infection after anterior cruciate ligament reconstruction (ACL-R) is a rare but severe complication. Despite an increase in articles published on this topic over the last decade, solid data to optimized diagnostic and therapeutic measures are scarce. For this reason, the European Bone and Joint Infection Society (EBJIS) and the European Society for Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) collaborated in order to develop recommendations for the diagnosis and management of infections after ACL-R. The aim of the workgroup was to perform a review of the literature and provide practical guidance to healthcare professionals involved in the management of infections after ACL-R. METHODS: An international workgroup was recruited to provide recommendations for predefined clinical dilemmas regarding the management of infections after ACL-R. MEDLINE, EMBASE, Cochrane Library and Scopus databases were searched for evidence to support the recommended answers to each dilemma. RESULTS: The recommendations were divided into two articles. The first covers etiology, prevention, diagnosis and antimicrobial treatment of septic arthritis following ACL-R and is primarily aimed at infectious disease specialists. This article includes the second part of the recommendations and covers prevention of infections after ACL-R, surgical treatment of septic arthritis following ACL-R and subsequent postoperative rehabilitation. It is aimed not only at orthopedic surgeons, but at all healthcare professionals dealing with patients suffering from infections after ACL-R. CONCLUSION: These recommendations guide clinicians in achieving timely and accurate diagnosis as well as providing optimal management, both of which are paramount to prevent loss of function and other devastating sequelae of infection in the knee joint. LEVEL OF EVIDENCE: V.

Minimal number of cultures needed to detect Cutibacterium acnes in primary reverse shoulder arthroplasty: a prospective study.

BACKGROUND: The objective of this study was to determine the minimum number of cultures needed to detect Cutibacterium acnes in primary reverse shoulder arthroplasties (RSAs). METHODS: It is a prospective study including 160 primary RSAs. Exclusion criteria included an active infection, an invasive shoulder treatment in the last 6 months before surgery, an Arthro-SCAN or Arthro-MRI in the last 6 months before surgery, previous shoulder surgeries and revision cases. In 90 cases, 11 cultures were obtained. Another 10 cultures were obtained in the other 70 cases (culture 10 was a sterile sponge to detect false positives). To determine the minimum number of cultures needed to detect C acnes, the prevalence of C acnes contamination of the 160 patients included was determined. RESULTS: There were 128 females and 32 males, with a mean age of 74 years. There were 1690 cultures obtained from the 160 primary RSA surgeries, and 132 of them turned out to be positive for C acnes. There were 42 patients with positive cultures. Twenty of them were males and 22 females. When considering the skin and the deep tissue cultures altogether, the prevalence of positive cultures for C acnes was of 26.25%. If only deep tissues cultures were considered, the prevalence of positive cultures for C acnes was of 23.13%. When considering the skin and the deep tissue cultures together, the sensitivity to detect the C acnes is 19% if only 1 culture is obtained, 31% if 2 cultures are obtained, 50% if 3 cultures are obtained, 59.5% if 4 cultures are obtained, 66.7% if 5 cultures are obtained, 73.8% if 6 cultures are obtained, 85.7% if 7 cultures are obtained, and 92.9% if 8 cultures are obtained. When considering only the deep tissue cultures, if only 1 culture is obtained, the sensitivity to detect the C acnes is 24.3%, 40.5% if 2 cultures are obtained, 54.1% if 3 cultures are obtained, 73% if 4 cultures are obtained, 89.2% if 5 cultures are obtained, and 97.3% if 6 or 7 cultures are obtained. DISCUSSION: A minimum number of 8 cultures are needed to detect C acnes in skin. Moreover, a minimum of 6 cultures are needed to detect it in deep tissues when performing an RSA.

Preoperative muscle thickness influences muscle activation after arthroscopic knee surgery.

PURPOSE: The aim of this study was to compare the correlation between preoperative quadriceps femoris muscle thickness and postoperative neuromuscular activation and quadriceps femoris strength in patients with and without patellofemoral pain after arthroscopic partial meniscectomy. METHODS: A series of 120 patients were prospectively analysed in a longitudinal cohort study of patients scheduled for arthroscopic partial meniscectomy. The patellofemoral pain group included patients who developed anterior knee pain after surgery while the control group included those who had not done so. Patients with preoperative patellofemoral pain, previous knee surgeries as well as those on whom additional surgical procedures had been performed were excluded. Of the 120 initially included in the study, 90 patients were analysed after the exclusions. RESULTS: There is a direct correlation between preoperative quadriceps femoris muscle thickness and the neuromuscular activity values and the strength of the muscle at 6 weeks after surgery. These results were seen exclusively in the group of patients who do not develop patellofemoral pain (0.543, p = 0.008). The group of patients who developed anterior knee pain in the postoperative period did not show this correlation (n.s.). CONCLUSION: In patients without patellofemoral pain after meniscectomy, the greater the preoperative thickness of the quadriceps femoris, the more postoperative neuromuscular activation and strength they had. This correlation did not occur in those patients who develop patellofemoral pain after meniscal surgery. LEVEL OF EVIDENCE: II.

High IGKC-Expressing Intratumoral Plasma Cells Predict Response to Immune Checkpoint Blockade.

Resistance to Immune Checkpoint Blockade (ICB) constitutes the current limiting factor for the optimal implementation of this novel therapy, which otherwise demonstrates durable responses with acceptable toxicity scores. This limitation is exacerbated by a lack of robust biomarkers. In this study, we have dissected the basal TME composition at the gene expression and cellular levels that predict response to Nivolumab and prognosis. BCR, TCR and HLA profiling were employed for further characterization of the molecular variables associated with response. The findings were validated using a single-cell RNA-seq data of metastatic melanoma patients treated with ICB, and by multispectral immunofluorescence. Finally, machine learning was employed to construct a prediction algorithm that was validated across eight metastatic melanoma cohorts treated with ICB. Using this strategy, we have unmasked a major role played by basal intratumoral Plasma cells expressing high levels of IGKC in efficacy. IGKC, differentially expressed in good responders, was also identified within the Top response-related BCR clonotypes, together with IGK variants. These results were validated at gene, cellular and protein levels; CD138+ Plasma-like and Plasma cells were more abundant in good responders and correlated with the same RNA-seq-defined fraction. Finally, we generated a 15-gene prediction model that outperformed the current reference score in eight ICB-treated metastatic melanoma cohorts. The evidenced major contribution of basal intratumoral IGKC and Plasma cells in good response and outcome in ICB in metastatic melanoma is a groundbreaking finding in the field beyond the role of T lymphocytes.

Evaluation of genetic models for COD and TSS estimation in wastewater through its spectrophotometric response.

In an urban wastewater treatment plant (WWTP), early knowledge of the pollutant load levels throughout the plant is key to optimize its processes and achieve better purification levels. Molecular spectrophotometry has begun to gain prominence in this wastewater characterization process, as it is a simple, fast, inexpensive and non-invasive technique. In this research work, different mathematical models based on genetic algorithms have been developed for the estimation of chemical oxygen demand (COD) and total suspended solids (TSS) from the spectral response of the samples, measured in the 380-700 nm range by means of a light-emitting diode (LED) spectrophotometer developed by the researchers. A field campaign was carried out in Mapocho-Trebal WWTP (Chile), where 550 samples were obtained in three different parts of the plant: at the inlet (raw wastewater), at the outlet (secondary treated wastewater) and at the outlet of the primary clarifier. A total of 18 estimation models have been calculated by mean of HeuristicLab software, which have presented a high accuracy, with a Pearson's coefficient between 80 and 90% in most cases. In order to achieve the most accurate models possible to characterize each part of the plant, specific models have also been developed, as well as combined models that are valid for all types of wastewater.

Adherence to a reliable PJI diagnostic protocol minimizes unsuspected positive cultures rate.

BACKGROUND: The aim of the present study was to evaluate the incidence of unsuspected PJI when prosthetic revisions are thoroughly evaluated by PJI dedicated orthopedic surgeon before surgery. The hypothesis is that the incidence of unsuspected PJI is reduced by applying this protocol. METHODS: This is a historical cohort study carried out in one university hospital. The prosthetic revision assessment was carried out in January 2019. From that date on, all patients that were programmed for hip or knee revision (either by an orthopedic surgeon specialized or not in septic revisions) were scheduled for a preoperative visit with the same orthopedic surgeon specialized in septic revisions. The diagnostic algorithm applied was based on the Pro-Implant Foundation diagnostic criteria. Prior to the revision assessment, the indication for joint aspiration was done at the surgeons' discretion (non-specialized in septic revisions) and the preoperative identification of PJI was also done by a hip or knee surgeon (not specialized in septic surgery). RESULTS: Based on the PIF criteria, there were 15 infections among the revisions in group 1 and 18 PJI in group 2 (p > 0.05). The most interesting finding was that there were 7 patients with unsuspected positive cultures in group 1. That represents 11% of all revisions. No patient in group 2 was found with unsuspected positive cultures (p < 0.001). CONCLUSION: A thorough PJI diagnostic algorithm should be implemented before prosthetic revision to avoid unsuspected positive cultures.

The vancomycin soaking technique: no differences in autograft re-rupture rate. A comparative study.

PURPOSE: The main aim of this study was to evaluate the re-rupture risk after an anterior cruciate ligament reconstruction (ACL-R) using the vancomycin soaking technique and to compare it with the re-rupture risk in patients on whom this technique was not utilized. The secondary purpose was to compare the functional outcomes of those two subsets of patients operated on for ACL-R. The hypotheses are that the vancomycin soaking technique does not affect the re-rupture risk or the functional outcomes. MATERIAL AND METHODS: A retrospective historical cohort study was conducted. Two groups were compared in terms of the re-rupture rate (traumatic or atraumatic) and functional outcomes (International Knee Documentation Committee (IKDC), Tegner, and Lysholm). Group 1 consisted of patients that received pre-operative IV antibiotics. In group 2, the patients received pre-operative IV antibiotics along with a graft that had been presoaked in a vancomycin solution. A minimum follow-up of five years was required. RESULTS: There were 17 patients that suffered a re-rupture in group 1 (4.7%) and 15 in group 2 (3.9%) (n.s.). IKDC was 82.0 in group 1 and 83.9 in group 2 (p = 0.049); Tegner scored 4 in both groups (n.s.) and Lysholm was 90.3 in group 1 and 92.0 in group 2 (p = 0.015). CONCLUSION: The vancomycin soaking technique for ACL autografts is a safe procedure for the daily clinical practice, in terms of re-ruptures. Moreover, it does not impair functional outcomes after an ACL-R.

The HOG MAPK pathway in Candida albicans: more than an osmosensing pathway.

In 1993, Brewster and Gustin described the existence of a kinase whose activity was essential for Saccharomyces cerevisiae to grow in environments with high osmolarity. This led to the discovery of the HOG pathway, a MAP kinase (MAPK) pathway that has been revealed to be crucial to respond to a wide range of stress conditions frequently encountered by fungi in their common habitats. MAPK signaling is initiated at the plasma membrane, where triggering stimuli lead to a phosphorylation cascade that ultimately activates transcription factors to ensure an appropriate adaptive response. In pathogenic fungi, the HOG pathway gains special significance as it is involved in traits related to pathogenicity; these include biofilm formation, adhesion to surfaces, and morphogenetic and epigenetic transitions. It also plays a role in controlling both the pathogen and the commensal state program. Understanding the signals leading to its activation, the elements of the pathways and the targets of the pathway are therefore of primary importance in the design of novel antifungals.

Wastewater Quality Estimation Through Spectrophotometry-Based Statistical Models.

Local administrations are increasingly demanding real-time continuous monitoring of pollution in the sanitation system to improve and optimize its operation, to comply with EU environmental policies and to reach European Green Deal targets. The present work shows a full-scale Wastewater Treatment Plant field-sampling campaign to estimate COD, BOD5, TSS, P, TN and NO3-N in both influent and effluent, in the absence of pre-treatment or chemicals addition to the samples, resulting in a reduction of the duration and cost of analysis. Different regression models were developed to estimate the pollution load of sewage systems from the spectral response of wastewater samples measured at 380-700 nm through multivariate linear regressions and machine learning genetic algorithms. The tests carried out concluded that the models calculated by means of genetic algorithms can estimate the levels of five of the pollutants under study (COD, BOD5, TSS, TN and NO3-N), including both raw and treated wastewater, with an error rate below 4%. In the case of the multilinear regression models, these are limited to raw water and the estimate is limited to COD and TSS, with less than a 0.5% error rate.

Performing Calibration of Transmittance by Single RGB-LED within the Visible Spectrum.

Spectrophotometry has proven to be an effective non-invasive technique for the characterization of the pollution load of sewer systems, enabling compliance with new environmental protection regulations. This type of equipment has costs and an energy consumption which make it difficult to place it inside a sewer network for real-time and massive monitoring. These shortcomings are mainly due to the use of incandescent lamps to generate the working spectrum as they often require the use of optical elements, such as diffraction gratings, to work. The search for viable alternatives to incandescent lamps is key to the development of portable equipment that is cheaper and with a lower consumption that can be used in different points of the sewer network. This research work achieved the following results in terms of the measured samples: First, the development a calibration procedure that enables the use of RGB-LED technology as a viable alternative to incandescent lamps, within the range of 510 to 645 nm, with high accuracy. Secondly, demonstration of a simple method to model the transmittance value of a specific wavelength without the need for optical elements, achieving a cost-effective equipment. Thirdly, it provides a simple method to obtain the transmittance based on the combination of RGB colors. Finally its viability is demonstrated for the spectral analysis of wastewater.

Which type of bone releases the most vancomycin? Comparison of spongious bone, cortical powder and cortico-spongious bone.

Bone infections can be challenging to treat and can lead to several surgeries and relapses. When a graft is needed, cavitary bone loss can be grafted with cancellous or cortical bone. Both can be used for grafting. However, the antibiotic releasing capacity of these grafts has not been compared. Which type of bone is best at releasing the most antibiotic has not been well established. The aim of this study was to determine which type of bone is best for antibiotic release when the bone is suffused with antibiotics by the surgeon. The hypothesis is that there would be a difference between the type of bone tested due to different release capacities of cortical and cancellous bone. This was an experimental study. Cortical spongy bone in chips, Spongy bone in chips and demineralized cortical bone powder were compared. For each type of bone, 5 samples were tested. Processed and decontaminated grafts were freeze-dried to be kept at room temperature. The primary endpoint was the amount of vancomycin released by the graft as it affects the concentration of antibiotic around the graft in clinical practice. The procedure for the study consisted of full graft immersion in a vancomycin solution. Then, the liquid was removed with aspiration. In order to measure the quantity of antibiotic released, the bone was put into distilled water in agitation in a heated rocker at 37 °C. After 30 min of soaking, 1 mL of the liquid was removed. The same extraction process was also carried out after 60 min soaking, 2 h, 3 h, 24 h, and 48 h. No differences were found between each type of bone relative to the concentration of vancomycin released at each time of the assessment. There was a significant difference in the weight of the bone with a higher weight for the cortical powder (1.793 g) versus cortical spongy bone and spongy bone (1.154 g and 1.013 g) with a p value < 0.0001. A significant difference was seen in the weight of the bone with vancomycin after the aspiration of the liquid with 3.026 g for cortical powder, 2.140 g and 2.049 g for the cortical spongy bone and the spongy bone with a p value < 0.0001. In daily clinical practice, one can use cancellous bone, cortico-cancellous bone or cortical powder in order to add vancomycin to a bone graft. Our results show the release kinetics of the soaked allografts. With a maximum of 14 mg/mL in the first minutes and a rapid decrease it shows a pattern comparable to antibiotic loaded bone cement. The method used appears favourable for prophylactic use, protecting the graft against contamination at implantation, but is not sufficient for treating chronic bone infection. LEVEL OF EVIDENCE: V.

The influence of local infiltration analgesia after total hip replacement. A randomized clinical trial.

To determine whether local infiltration analgesia by catheter infusion was superior to conventional analgesia in terms of postoperative pain control after THR. A randomized double-blind clinical trial was performed. There were four groups based on catheter placement and the infusion constituents : 1) Intraarticular catheter + anesthetics ; 2) Intraarticular catheter +placebo ; 3) Subfascial catheter + anesthetics ; 4) Subfascial catheter + placebo. The anesthetic infusion contained bupivacaine (bolus + continuous perfusion up to 36 hours). The placebo solution was physiological serum. The same conventional analgesic schedule was prescribed to all patients. Pain was evaluated by means of PCA shots and the VAS. Side effects, time to start rehabilitation and time to discharge were also analyzed. 100 patients (25 for group). Mean age was 67 years old (SD 12 y/o) and 53% were male. Mean PCA shots was 27 [range 2-87] and mean VAS was 1 [range 0-7]. No differences were found (p>0.05) when these variables were compared between the groups. The use of LIA with bupivacaine using a catheter infusion does not provide better pain control after THR.

S100-A9 protein in exosomes from chronic lymphocytic leukemia cells promotes NF-κB activity during disease progression.

Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by accumulation of clonal B lymphocytes, resulting from a complex balance between cell proliferation and apoptotic death. Continuous crosstalk between cancer cells and local/distant host environment is required for effective tumor growth. Among the main actors of this dynamic interplay between tumoral cells and their microenvironment are the nano-sized vesicles called exosomes. Emerging evidence indicates that secretion, composition, and functional capacity of exosomes are altered as tumors progress to an aggressive phenotype. In CLL, no data exist exploring the specific changes in the proteomic profile of plasma-derived exosomes from patients during disease evolution. We hereby report for the first time different proteomic profiles of plasma exosomes, both between indolent and progressive CLLs as well as within the individual patients at the onset of disease and during its progression. Next, we focus on the changes of the exosome protein cargoes, which are found exclusively in patients with progressive CLL after disease progression. The alterations in the proteomic cargoes underline different networks specific for leukemia progression related to inflammation, oxidative stress, and NF-κB and phosphatidylinositol 3-kinase/AKT pathway activation. Finally, our results suggest a preponderant role for the protein S100-A9 as an activator of the NFκB pathway during CLL progression and suggest that the leukemic clone can generate an autoactivation loop through S100-A9 expression, NF-κB activation, and exosome secretion. Collectively, our data propose a new pathway for NF-κB activation in CLL and highlight the importance of exosomes as extracellular mediators promoting tumor progression in CLL.