CCR5 deficiency impairs CD4+ T-cell memory responses and antigenic sensitivity through increased ceramide synthesis.

CCR5 is not only a coreceptor for HIV-1 infection in CD4+ T cells, but also contributes to their functional fitness. Here, we show that by limiting transcription of specific ceramide synthases, CCR5 signaling reduces ceramide levels and thereby increases T-cell antigen receptor (TCR) nanoclustering in antigen-experienced mouse and human CD4+ T cells. This activity is CCR5-specific and independent of CCR5 co-stimulatory activity. CCR5-deficient mice showed reduced production of high-affinity class-switched antibodies, but only after antigen rechallenge, which implies an impaired memory CD4+ T-cell response. This study identifies a CCR5 function in the generation of CD4+ T-cell memory responses and establishes an antigen-independent mechanism that regulates TCR nanoclustering by altering specific lipid species.

The Intergroup Value Protection Model: A Theoretically Integrative and Dynamic Approach to Intergroup Conflict Escalation in Democratic Societies.

SCIENTIFIC ABSTRACT: We review social-psychological evidence for a theoretically integrative and dynamic model of intergroup conflict escalation within democratic societies. Viewing individuals as social regulators who protect their social embeddedness (e.g., in their group or in society), the intergroup value protection model (IVPM) integrates key insights and concepts from moral and group psychology (e.g., group identification, outrage, moralization, protest) into a functional intergroup value protection process. The model assumes that social regulators are continuously looking for information diagnostic of the outgroup's intentions to terminate the relationship with the ingroup, and that their specific cognitive interpretations of an outgroup's action (i.e., as a violation of ingroup or shared values) trigger this process. The visible value-protective responses of one group can trigger the other group's value-protective responses, thus dynamically increasing chances of conflict escalation. We discuss scientific implications of integrating moral and group psychology and practical challenges for managing intergroup conflict within democratic societies. PUBLIC ABSTRACT: The 2021 Capitol Hill attack exemplifies a major "trigger event" for different groups to protect their values within a democratic society. Which specific perceptions generate such a triggering event, which value-protective responses does it trigger, and do such responses escalate intergroup conflict? We offer the intergroup value protection model to analyze the moral and group psychology of intergroup conflict escalation in democratic societies. It predicts that when group members cognitively interpret another group's actions as violating ingroup or shared values, this triggers the intergroup value protection process (e.g., increased ingroup identification, outrage, moralization, social protest). When such value-protective responses are visible to the outgroup, this can in turn constitute a trigger event for them to protect their values, thus increasing chances of intergroup conflict escalation. We discuss scientific implications and practical challenges for managing intergroup value conflict in democratic societies, including fears of societal breakdown and scope for social change.

Mechanism of escape from the antibacterial activity of metal-based nanoparticles in clinically relevant bacteria: A systematic review.

The emergency of antibiotic-resistant bacteria in severe infections is increasing, especially in nosocomial environments. The ESKAPE group is of special importance in the groups of multi-resistant bacteria due to its high capacity to generate resistance to antibiotics and bactericides. Therefore, metal-based nanomaterials are an attractive alternative to combat them because they have been demonstrated to damage biomolecules in the bacterial cells. However, there is a concern about bacteria developing resistance to NPs and their harmful effects due to environmental accumulation. Therefore, this systematic review aims to report the clinically relevant bacteria that have developed resistance to the NPs. According to the results of this systematic review, various mechanisms to counteract the antimicrobial activity of various NP types have been proposed. These mechanisms can be grouped into the following categories: production of extracellular compounds, metal efflux pumps, ROS response, genetic changes, DNA repair, adaptative morphogenesis, and changes in the plasma membrane.

Neutrophil Extracellular Trap-related Biomarkers Are Increased in the Synovial Fluid of Patients With Periprosthetic Joint Infections.

BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) is a major challenge in clinical practice. The role of neutrophils in fighting infection has been increasingly understood, and one mechanism of action of these cells is neutrophil extracellular traps. However, little is known about this process in PJI. QUESTIONS/PURPOSES: (1) Are the biomarkers of neutrophil extracellular trap formation (citrullinated histone H3 [H3Cit], cell-free DNA [cf-DNA], and myeloperoxidase [MPO]) increased in the synovial fluid of patients with PJI? (2) What is the diagnostic accuracy of biomarkers of neutrophil extracellular trap formation for PJI? METHODS: Between May 2020 and March 2021, 43 patients who underwent revision THA or TKA were enrolled in this study. Eleven patients were excluded and 32 patients were categorized into the PJI group (n = 16) or non-PJI group (n = 16) according to the 2018 Second International Consensus Meeting on Musculoskeletal Infection criteria. There were 15 men and 17 women in this study, with a median (range) age of 70 years (60 to 80 years). Twenty-seven patients had TKA and five had THA. We measured cf-DNA, MPO, and H3Cit in synovial fluid. The sensitivity, specificity, and receiver operating characteristic curve were calculated for each biomarker using the Musculoskeletal Infection Society criteria as the gold standard for diagnosis and considering a clinical surveillance of 2 years for patients in the non-PJI group. RESULTS: Patients with PJI had higher levels of synovial fluid cf-DNA (median [range] 130 ng/µL [18 to 179] versus 2 ng/µL [0 to 6]; p < 0.001), MPO (1436 ng/µL [55 to 3996] versus 0 ng/µL [0 to 393]; p < 0.001), and H3Cit (2115 ng/µL [5 to 2885] versus 3 ng/µL [0 to 87]; p < 0.001) than those in the non-PJI group. In receiver operating characteristic curve analyses, we observed near-perfect performance for all biomarkers evaluated, with an area under the curve of 1 (95% CI 0.9 to 1), 0.98 (95% CI 0.9 to 1), and 0.94 (95% CI 0.8 to 0.99) for cf-DNA, MPO, and H3Cit, respectively. The sensitivity for detecting PJI using synovial fluid was 100% for cf-DNA, 94% for MPO, and 88% for H3Cit. The specificity was 100% for cf-DNA and MPO, and 88% for H3Cit. CONCLUSION: Our results show that neutrophils in the periprosthetic microenvironment release neutrophil extracellular traps as part of the bactericidal arsenal to fight infection. These results allow a better understanding of the cellular and molecular processes that occur in this microenvironment, enabling the design of more assertive strategies for identifying new biomarkers and improving the available ones. Novel studies are needed to define whether and how neutrophil extracellular trap-related biomarkers can be useful for diagnosing PJI. LEVEL OF EVIDENCE: Level II, diagnostic study.

Translational profile of developing phellem cells in Arabidopsis thaliana roots.

The phellem is a specialized boundary tissue providing the first line of defense against abiotic and biotic stresses in organs undergoing secondary growth. Phellem cells undergo several differentiation steps, which include cell wall suberization, cell expansion, and programmed cell death. Yet, the molecular players acting particularly in phellem cell differentiation remain poorly described, particularly in the widely used model plant Arabidopsis thaliana. Using specific marker lines we followed the onset and progression of phellem differentiation in A. thaliana roots and further targeted the translatome of newly developed phellem cells using translating ribosome affinity purification followed by mRNA sequencing (TRAP-SEQ). We showed that phellem suberization is initiated early after phellogen (cork cambium) division. The specific translational landscape was organized in three main domains related to energy production, synthesis and transport of cell wall components, and response to stimulus. Novel players in phellem differentiation related to suberin monomer transport and assembly as well as novel transcription regulators were identified. This strategy provided an unprecedented resolution of the translatome of developing phellem cells, giving a detailed and specific view on the molecular mechanisms acting on cell differentiation in periderm tissues of the model plant Arabidopsis.

Malignant Primary and Metastatic Cardiac Tumors: A Single-Center 27-Year Case Review.

BACKGROUND: Malignant primary cardiac tumors are exceedingly rare, and despite surgical exeresis or chemotherapy, their prognosis remains poor. Cardiac invasion by metastatic tumors, while more common, also entails an unsatisfactory outcome. This study aimed to review patients diagnosed with malignant primary and secondary cardiac tumors in a tertiary center between 1995 and 2022. METHODS: Clinical data, echocardiographic, computed tomography, and magnetic resonance assessments of tumor location and morphology, histology, treatment, and survival were retrospectively analyzed. RESULTS: Sixty malignant cardiac tumors were diagnosed: 17 primary (A) and 43 metastatic (B) tumors. A: the most common types were angiosarcoma (41%), undifferentiated sarcoma (23%), and fibrosarcoma (18%). Patients with primary tumors were younger than patients with metastatic tumors (41 ± 13 years vs. 57 ± 18 years, p = 0.001), with no significant gender difference. The most frequent presentations were heart failure (59%) and arrhythmia (23%). The most prevalent tumor location was the right heart chambers (71%), mostly in the right atrium (35%). 47% were submitted to tumor resection, and 29% received chemotherapy. The mortality rate was 82% with a median survival of 6.0 (interquartile range: 1.0-11.8) months after diagnosis (minimum of 12 days and maximum of 19 years). One patient with fibrosarcoma underwent heart transplantation and was still alive and well after 19 years. B: regarding metastatic cardiac invasion, the most common primary tumor sites were lung carcinomas (38%), thymomas (17%), and lymphomas (14%). Presentation with pericardial effusion was common (33%). The mortality rate was 72%, with a median survival of 3.6 (1.0-13.4) months (minimum of 7 days, maximum of 5 years). CONCLUSION: Diagnosis of metastatic cardiac tumors was more common than that of malignant primary tumors, both with a dismal prognosis. When radical exeresis is not possible, heart transplantation can be an option with a favorable outcome in carefully selected patients with sarcomas.

In vitro assessment of antibacterial and antiviral activity of three copper products after 200 rounds of simulated use.

Copper has well-documented antibacterial effects but few have evaluated it after prolonged use and against bacteria and viruses. Coupons from three copper formulations (solid, thermal coating, and decal applications) and carbon steel controls were subjected to 200 rounds simulated cleaning using a Wiperator™ and either an accelerated hydrogen peroxide, quaternary ammonium, or artificial sweat products. Antibacterial activity against S. aureus and P. aeruginosa was then evaluated using a modified Environmental Protection Agency protocol. Antiviral activity against coronavirus (229E) and norovirus (MNV-1) surrogates was assessed using the TCID50 method. Results were compared to untreated control coupons. One hour after inoculation, S. aureus exhibited a difference in log kill of 1.16 to 4.87 and P. aeruginosa a log kill difference of 3.39-5.23 (dependent upon copper product and disinfectant) compared to carbon steel. MNV-1 demonstrated an 87-99% reduction on each copper surfaces at 1 h and 99% reduction at 2 h compared to carbon steel. Similarly, coronavirus 229E exhibited a 97-99% reduction after 1 h and 90-99% after 2 h. Simulated use with artificial sweat did not hinder the antiviral nor the antibacterial activity of Cu surfaces. Self-sanitizing copper surfaces maintained antibacterial and antiviral activity after 200 rounds of simulated cleaning.

Hypolipidemic potential and safety profile of the ethanolic extract and flour of the peel of Passiflora Cincinnata Mast. (Passifloraceae) in mice.

Passiflora cincinnata Mast. is described as a native Caatinga species, used by nutritional and medicinal purposes, although there are still few studies and pharmacological data related to this species. This paper aims to evaluate the safety profile and hypolipidemic potential of the fruit peel of this species in mice. It was analyzed the chemical composition of ethanolic extract (EtOH-Pc) by HPLC-DAD-MS/MS, and the organic and inorganic composition of flour (MF-Pc). Also were evaluated the acute toxicity, the lipid-lowering potential of these samples, through of a pretreatment (oral: 100 and 200 mg/kg), and a single treatment with the same doses, after hyperlipidemic induction with triton WR-1339, using as animal model Swiss Mus musculus mice, besides histopathological analysis. The presence of flavonoids in the extract was confirmed, mainly C-glycosides, and antioxidant minerals and pectin, in flour. No clinical signs of toxicity or death were reported in the study. In the hyperlipidemia study model used, the analyzed substances, at all doses, notably decreased the lipid levels of TC, TG, LDL-c and VLDL-c and increase the HDL-c levels in the induced hyperlipidemic mice (p < 0.05). The results of the histopathological analysis showed that in the group only induced was identified the discrete presence of hepatic steatosis, in 2 animals at the analysis of 24 h, not being visualized in the groups treated with the substances evaluated. The results obtained in the present study suggest a hypolipidemic potential of the extract and flour, obtained from the fruit peel of Passiflora cincinnata Mast.

The Novel RXR Agonist MSU-42011 Differentially Regulates Gene Expression in Mammary Tumors of MMTV-Neu Mice.

Retinoid X receptor (RXR) agonists, which activate the RXR nuclear receptor, are effective in multiple preclinical cancer models for both treatment and prevention. While RXR is the direct target of these compounds, the downstream changes in gene expression differ between compounds. RNA sequencing was used to elucidate the effects of the novel RXRα agonist MSU-42011 on the transcriptome in mammary tumors of HER2+ mouse mammary tumor virus (MMTV)-Neu mice. For comparison, mammary tumors treated with the FDA approved RXR agonist bexarotene were also analyzed. Each treatment differentially regulated cancer-relevant gene categories, including focal adhesion, extracellular matrix, and immune pathways. The most prominent genes altered by RXR agonists positively correlate with survival in breast cancer patients. While MSU-42011 and bexarotene act on many common pathways, these experiments highlight the differences in gene expression between these two RXR agonists. MSU-42011 targets immune regulatory and biosynthetic pathways, while bexarotene acts on several proteoglycan and matrix metalloproteinase pathways. Exploration of these differential effects on gene transcription may lead to an increased understanding of the complex biology behind RXR agonists and how the activities of this diverse class of compounds can be utilized to treat cancer.

Targeting SARS-CoV-2 Non-Structural Proteins.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped respiratory ß coronavirus that causes coronavirus disease (COVID-19), leading to a deadly pandemic that has claimed millions of lives worldwide. Like other coronaviruses, the SARS-CoV-2 genome also codes for non-structural proteins (NSPs). These NSPs are found within open reading frame 1a (ORF1a) and open reading frame 1ab (ORF1ab) of the SARS-CoV-2 genome and encode NSP1 to NSP11 and NSP12 to NSP16, respectively. This study aimed to collect the available literature regarding NSP inhibitors. In addition, we searched the natural product database looking for similar structures. The results showed that similar structures could be tested as potential inhibitors of the NSPs.

The Tumor Immune Microenvironment in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a type of kidney cancer that arises from the cells lining the tubes of the kidney. The tumor immune microenvironment (TIME) of ccRCC is a complex interplay of various immune cells, cytokines, and signaling pathways. One of the critical features of the ccRCC TIME is the presence of infiltrating immune cells, including T cells, B cells, natural killer cells, dendritic cells, and myeloid-derived suppressor cells. Among these cells, CD8+ T cells are particularly important in controlling tumor growth by recognizing and killing cancer cells. However, the TIME of ccRCC is also characterized by an immunosuppressive environment that hinders the function of immune cells. Several mechanisms contribute to the immunosuppressive nature of the ccRCC TIME. For instance, ccRCC cells produce cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-ß), which suppress immune cell activation and promote the differentiation of regulatory T cells (Tregs). Tregs, in turn, dampen the activity of effector T cells and promote tumor growth. In addition, ccRCC cells can express programmed death-ligand 1 (PD-L1), which interacts with the programmed cell death protein 1 (PD-1) receptor on T cells to inhibit their function. In addition, other immune checkpoint proteins, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and lymphocyte activation gene 3 (LAG-3), also contribute to the immunosuppressive milieu of the ccRCC TIME. Finally, the hypoxic and nutrient-poor microenvironment of ccRCC can stimulate the production of immunosuppressive metabolites, such as adenosine and kynurenine, which further impair the function of immune cells. Understanding the complex interplay between tumor cells and the immune system in the ccRCC TIME is crucial for developing effective immunotherapies to treat this disease.

Antimicrobial activity of the Flo peptide produced in Scenedesmus acutus and Nannochloropsis oculata.

The continuous increase of bacterial pathogen resistance to conventional antibiotics has challenged the research community to develop new antimicrobial strategies. Antimicrobial peptides (AMP) are a promising alternative to combat multidrug-resistant strains compared to conventional antibiotics because of their biocompatibility. In the present study, the Flo peptide, an AMP from the Moringa oleifera tree, was expressed in the chloroplast of the microalgae Nannochloropsis oculata and Scenedesmus acutus. The transgene insertion was verified by PCR amplification, and the homoplasmy was corroborated in spectinomycin-resistant lines. The identification and quantification of the peptide were performed using ELISA. The antimicrobial activity was studied against the Gram-negative Escherichia coli (ATCC 25,922) and Klebsiella pneumoniae (ATCC 700,603). The inflammatory response of the total soluble proteins of transplastomic N. oculata was assessed by measuring secretion of the cytokines IL-6, IL-10, and alpha-tumor necrosis (TNF-α), and cytotoxicity was assessed. These results provide a potential strategy to produce the Flo peptide in microalgae with antibacterial activities.

Cell-free Deoxyribonucleic Acid: A Potential Biomarker of Chronic Periprosthetic Knee Joint Infection.

BACKGROUND: The correct diagnosis of a chronic periprosthetic joint infection (PJI) is a major challenge in clinical practice, with the "gold standard" for diagnosis yet to be established. Synovial fluid analysis has been proven to be a useful tool for that purpose. Cell-free DNA (cf-DNA) levels have been shown to be increased in several conditions such as cancer, trauma, and sepsis. Therefore, this study was designed to evaluate the potential of synovial fluid cf-DNA quantification for the diagnosis of chronic periprosthetic infections following total knee arthroplasty. METHODS: A prospective study with patients undergoing total knee arthroplasty revision surgery for any indication was performed. PJI diagnosis was defined according to the Second International Consensus Meeting on Musculoskeletal Infection (2018) criteria. The study cohort consisted of 26 patients classified as infected and 40 as noninfected. Synovial fluid cf-DNA direct quantification by fluorescent staining was made. Sensitivity, specificity, and receiver operating characteristic curve were calculated. RESULTS: The cf-DNA levels were significantly higher in patients who had PJIs (122.5 ± 57.2 versus 4.6 ± 2.8 ng/µL, P < .0001). With a cutoff of 15 ng/µL, the area under the receiver operating characteristic, sensitivity, and specificity of cf-DNA were 0.978, 96.2%, and 100%, respectively. CONCLUSION: The present study has shown that cf-DNA is increased in synovial fluid of patients who have chronic PJIs. It is a promising biomarker for knee PJI diagnosis and further studies are needed to confirm its utility.

Burkholderia vietnamiensis G4 as a biological agent in bioremediation processes of polycyclic aromatic hydrocarbons in sludge farms.

Polycyclic aromatic hydrocarbons (PAHs) are one of the main pollutants generated by the refining and use of oil. To search bioremediation alternatives for these compounds, mainly in situ, considering the biotic and abiotic variables that affect the contaminated sites is determinant for the success of bioremediation techniques. In this study, bioremediation strategies were evaluated in situ, including biostimulation and bioaugmentation for 16 priority PAHs present in activated sludge farms. B. vietnamiensis G4 was used as a biodegradation agent for bioaugmentation tests. The analyses occurred for 12 months, and temperature and humidity were measured to verify the effects of these factors on the biodegradation. We used the technique GC-MS to evaluate and quantify the degradation of PAHs over the time of the experiment. Of the four treatments applied, bioaugmentation with quarterly application proved to be the best strategy, showing the degradation of compounds of high (34.4% annual average) and low (21.9% annual average) molecular weight. A high degradation rate for high molecular weight compounds demonstrates that this technique can be successfully applied in bioremediation of areas with compounds considered toxic and stable in nature, contributing to the mitigation of impacts generated by PAHs.

Syncytin-1/HERV-W envelope is an early activation marker of leukocytes and is upregulated in multiple sclerosis patients.

Syncytin-1 is the envelope protein of the human endogenous retrovirus W (HERV-W). It has been related to multiple sclerosis (MS) but its role in cellular immunity and its pathogenic mechanism in the autoimmune context are not fully understood. We analyzed syncytin-1 levels in peripheral blood mononuclear cells (PBMC) subsets from healthy donors, MS patients in relapse or remission, and patients with acute infections by flow cytometry. PBMC cultures were also prepared to analyze protein expression kinetics. MS patients had higher levels of syncytin-1 levels than controls. We found that syncytin-1 is elevated in monocytes during MS relapses and infections. Cells expressing syncytin-1, including monocytes, T and B lymphocytes, and NKs presented mainly an activated phenotype and, upon stimulation with LPS, its levels increased rapidly on antigen-presenting cells. Syncytin-1 ligation promoted the activation of monocytes, as demonstrated by the upregulation of CD80 and the nonclassical subset CD14low CD16+ . Our results suggest an important role for syncytin-1 in the activation of leukocytes. Given that the expression of syncytin-1 is upregulated in MS patients, this protein might be contributing to the autoimmune cascade in the disease.

Identification of the Active Principle Conferring Anti-Inflammatory and Antinociceptive Properties in Bamboo Plant.

Early plants began colonizing earth about 450 million years ago. During the process of coevolution, their metabolic cellular pathways produced a myriad of natural chemicals, many of which remain uncharacterized biologically. Popular preparations containing some of these molecules have been used medicinally for thousands of years. In Brazilian folk medicine, plant extracts from the bamboo plant Guadua paniculata Munro have been used for the treatment of infections and pain. However, the chemical basis of these therapeutic effects has not yet been identified. Here, we performed protein biochemistry and downstream pharmacological assays to determine the mechanisms underlying the anti-inflammatory and antinociceptive effects of an aqueous extract of the G. paniculata rhizome, which we termed AqGP. The anti-inflammatory and antinociceptive effects of AqGP were assessed in mice. We identified and purified a protein (AgGP), with an amino acid sequence similar to that of thaumatins (~20 kDa), capable of repressing inflammation through downregulation of neutrophil recruitment and of decreasing hyperalgesia in mice. In conclusion, we have identified the molecule and the molecular mechanism responsible for the anti-inflammatory and antinociceptive properties of a plant commonly used in Brazilian folk medicine.

New benzo(a)pyrene-degrading strains of the Burkholderia cepacia complex prospected from activated sludge in a petrochemical wastewater treatment plant.

The prospection of bacteria that are resistant to polyaromatic hydrocarbons (PAH) of activated sludge from a Petrochemical Wastewater Treatment Plant (WWTP) allows investigating potential biodegraders of PAH. For this purpose, sludge samples were cultured with benzo(a)pyrene and/or naphthalene as carbon sources. The recovered isolates were characterized by biochemical methods and identified based on the analysis of the sequence of three genes: 16S, recA and gyrB. The isolated strains were shown to be capable of producing surfactants, which are important for compound degradation. The ability to reduce benzo(a)pyrene in vitro was tested by gas chromatography. After 20 days of experiment, the consortium that was enriched with 1 mg/L of benzo(a)pyrene was able to reduce 30% of the compound when compared to a control without bacteria. The four isolated strains that significantly reduced benzo(a)pyrene belong to the Burkholderia cepacia complex and were identified within the consortium as the species B. cenocepacia IIIa, B. vietnamiensis, B. cepacia, and B. multivorans. This finding demonstrates the biotechnological potential of the B. cepacia complex strains for use in wastewater treatment and bioremediation. Previous studies on hydrocarbon-degrading strains focused mainly on contaminated soil or marine areas. In this work, the strains were prospected from activated sludge in a WWTP and showed the potential of indigenous samples to be used in both improving treatment systems and bioremediation of areas contaminated with petrochemical waste.

A Patient-Based National Survey and Prospective Evaluation of Postoperative Pain Management in Spain: Prevalent but Possibly Preventable.

OBJECTIVE: To evaluate the national general prevalence of postoperative pain and the associated organizational/structural factors related to the provision of health care services. DESIGN AND SETTING: Observational prospective cohort study performed in 46 tertiary hospitals that were randomly selected from the Spanish National Inventory of Hospitals through a two-stage balanced and stratified procedure. SUBJECTS AND METHODS: Nine-hundred surgical patients representing a wide spectrum of surgical procedures and anesthetic methods were recruited. Those suffering moderate or worse pain while in the postanesthesia care unit/surgery ward (PACU/SW) were followed for 72 hours. Site characteristics were also surveyed. Multilevel models were used to evaluate center- and patient-level factors associated with pain and quality of recovery (QoR). Weighted generalized estimating equations were used to analyze the evolution of pain intensity. RESULTS: The prevalence while in and at discharge from the PACU/SW was 48.7% (cluster-adjusted 95% confidence interval [CI] = 38.1-59.2%) and 21.6% (95% CI = 15.4-27.8%), respectively. Pain intensity decreased significantly over time. Less than 20% of the patients received systemic patient-controlled analgesia (PCA) or regional analgesic techniques. Age, preexisting pain, type of surgery, use of general anesthesia, and postoperative potent opioids were associated with pain risk and intensity, as were center-level factors such as patient information, protocol availability, and coordination of care. In turn, QoR was related to pain intensity and patient satisfaction with analgesia and side effects. CONCLUSIONS: Compared with previous reports, the prevalence of moderate/severe postoperative pain has decreased but remains excessive. Organizational improvements to deploy procedure-specific, opioid-sparing analgesic strategies including regional techniques are recommended.

A new device for patellofemoral instrumented stress-testing provides good reliability and validity.

PURPOSE: To evaluate the reliability of an instrumented patellofemoral (PF) stress-testing-the Porto Patellofemoral Testing Device (PPTD)-and validate the instrumented assessment method comparing to manual physical examination. METHODS: Eight asymptomatic volunteers underwent bilateral PF-instrumented examination with the PPTD and magnetic resonance imaging (MRI) to assess intra-rater reliability of the instrumented assessment methodology. Six patients with unilateral PF instability underwent physical examination and PPTD concomitantly with MRI. Manual examination was performed by two blinded surgeons and compared with PPTD test. Ligament stiffness was calculated and compared between injured and non-injured lower limbs. RESULTS: PPTD showed a pre-determined and reproducible stress-force application with excellent intra-rater agreement (intra-class correlation coefficient 0.83-0.98). The manual exam was imprecise with variable examiner-dependent stress-force application. The PPTD resulted in greater lateral patellar translation (converted in quadrants) than manual exam for patients that have reached maximum translation force. Measurement of patellar position and displacement using PPTD was more accurate and precise than the visual estimation of translated quadrants by manual exam. Ligament stiffness curves showed no relevant changes in patellar displacement after 62 N. CONCLUSION: The PPTD instrumented stress-testing is a valid device to quantify PF position and displacement with high intra-rater reliability, showing more accuracy, more precision and less variability than physical examination. This device provides an accurate and objective measure to quantify the patellar movement which can augment the physical examination procedures and assist clinicians in the management of decision-making and in the assessment of post-treatment outcomes of PF pathological conditions.

Unilateral anterior knee pain is associated with increased patellar lateral position after stressed lateral translation.

PURPOSE: To objectively compare side-to-side patellar position and mobility in patients with idiopathic unilateral anterior knee pain (AKP) using a stress-testing device concomitantly with magnetic resonance imaging. It is hypothesized that the painful knees present greater patellar mobility than the contralateral non-painful knees. METHODS: From a total sample of 359 patients, 23 patients with idiopathic unilateral AKP (30.9 years, 23.4 kg/m2, 43% males) were included within the present study. Both knees of all the patients were examined by conventional imaging, including the measurement of trochlear sulcus angle, Caton-Deschamps index, tibial tuberosity to trochlear groove distance, patellar tilt angle and patellar subluxation (both at rest and upon quadriceps contraction). Additionally, the same patients underwent stress testing (Porto Patella Testing Device); these measurements were taken with the patella at rest, after lateral patellar translation and after lateral patellar tilt. Clinical and functional outcomes were obtained using physical examination and the Kujala and Lysholm scores. RESULTS: Painful knees showed statistically significant higher patellar lateral position after stressed lateral translation than non-painful knees (p = 0.028), 9.8 ± 3.6 mm and 7.1 ± 6.3 mm, respectively. The adjusted multivariate logistic model identified the patellar position after lateral displacement to be significantly associated with AKP (OR = 1.165) and the model (AUC = 0.807, p < 0.001) showed reasonable sensitivity (67%) and specificity (73%). CONCLUSION: Patients with idiopathic unilateral AKP with morphologically equivalent knees showed statistically significant increased patellar lateral position after stressed lateral displacement in their painful knee. The greater lateral patellar mobility quantified by the PPTD testing brings more objectivity to the diagnosis. LEVEL OF EVIDENCE: II.