Reverse Correlation Characterizes More Complete Tinnitus Spectra in Patients.

Goal: We validate a recent reverse correlation approach to tinnitus characterization by applying it to individuals with clinically-diagnosed tinnitus. Methods: Two tinnitus patients assessed the subjective similarity of their non-tonal tinnitus percepts and random auditory stimuli. Regression of the responses onto the stimuli yielded reconstructions which were evaluated qualitatively by playing back resynthesized waveforms to the subjects and quantitatively by response prediction analysis. Results: Subject 1 preferred their resynthesis to white noise; subject 2 did not. Response prediction balanced accuracies were significantly higher than chance across subjects: subject 1: 0.5963, subject 2: 0.6922. Conclusion: Reverse correlation can provide the foundation for reconstructing accurate representations of complex, non-tonal tinnitus in clinically diagnosed subjects. Further refinements may yield highly similar waveforms to individualized tinnitus percepts.

Impaired fatty acid import or catabolism in macrophages restricts intracellular growth of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular Mtb utilize host derived fatty acids and cholesterol to fuel the majority of its metabolic demands, the role of macrophage lipid catabolism on the bacteria's ability to access the intracellular lipid pool remains undefined. We utilized a CRISPR genetic knockdown approach to assess the impact of sequential steps in fatty acid metabolism on the growth of intracellular Mtb. Our analyzes demonstrate that knockdown of lipid import, sequestration and metabolism genes collectively impair the intracellular growth of Mtb in macrophages. We further demonstrate that modulating fatty acid homeostasis in macrophages impairs Mtb replication through diverse pathways like enhancing production of pro- inflammatory cytokines, autophagy, restricting the bacteria access to nutrients and increasing oxidative stress. We also show that impaired macrophage lipid droplet biogenesis is restrictive to intracellular Mtb replication, but increased induction of the same by blockade of downstream fatty acid oxidation fails to rescue Mtb growth. Our work expands our understanding of how host fatty acid homeostasis impacts Mtb growth in the macrophage.

Cementless Total Knee Arthroplasty: A State-of-the-Art Review.

¼ The demographic profile of candidates for total knee arthroplasty (TKA) is shifting toward younger and more active individuals.¼ While cemented fixation remains the gold standard in TKA, the interest is growing in exploring cementless fixation as a potentially more durable alternative.¼ Advances in manufacturing technologies are enhancing the prospects for superior long-term biological fixation.¼ Current research indicates that intermediate to long-term outcomes of modern cementless TKA designs are comparable with traditional cemented designs.¼ The selection of appropriate patients is critical to the success of cementless fixation techniques in TKA.¼ There is a need for high-quality research to better understand the potential differences and relative benefits of cemented vs. cementless TKA systems.

Fuzzy and spatial analysis of cutaneous leishmaniasis in Pará State, Brazilian Amazon: an ecological and exploratory study.

INTRODUCTION: This study sought to analyze the relationships between cutaneous leishmaniasis and its epidemiological, environmental and socioeconomic conditions, in the 22 microregions of Pará state, Brazil, for the period from 2017 to 2022. METHODOLOGY: In this ecological and exploratory study, the microregions were used as spatial units because they are formed by contiguous municipalities with similar characteristics. The epidemiological, environmental, socioeconomic, and public health policy data employed were obtained from the official information systems at the Ministry of Health, National Institute for Space Research, and Brazilian Institute of Geography and Statistics. A fuzzy system was developed to identify risk factors for the disease, using Python programming language. The results were analyzed with the bivariate Global Moran spatial analysis technique. RESULTS: It was observed that the Altamira microregion had the highest risk percentage for the disease, while Breves had the lowest, with significant differences in the relevance of its conditioning factors, mainly related to land use and cover patterns, in addition to demography and living conditions index, education and public health policies. CONCLUSIONS: The fuzzy system associated with the geostatistical technique was satisfactory for identifying areas with health vulnerability gradients related to deforestation, pasture, poverty, illiteracy, and health services coverage, as its conditioning variables. Thus, it was demonstrated that deforestation was the main risk factor for the disease. The system can also be used in environmental and epidemiological surveillance.

Risk factors for failure of manipulation under anesthesia after total knee arthroplasty.

BACKGROUND: Manipulation under anesthesia (MUA) is a well-established treatment for stiffness after total knee arthroplasty (TKA). Risk factors for failure of MUA remain largely unknown. The primary aim of this study was to identify risk factors for failure of MUA after TKA. METHODS: We performed a retrospective cohort study including 470 patients who underwent MUA after primary TKA with minimum 2 year follow-up. Patients were grouped into success (n = 412) or failure (n = 58) cohorts; failure was defined as flexion < 90° at most recent follow-up or revision for stiffness. The increase in flexion post-MUA for the cohort was calculated. Several clinical, patient, and surgical factors were analyzed using univariate, followed by multivariable logistic regression models to identify independent risk factors associated with failure. RESULTS: The mean increase in flexion was 42° (range 0-115). BMI 30-35 (p = 0.01, odds ratio (OR) 2.42; 95% CI 1.25-4.68) and poorer pre-MUA flexion (p < 0.01, OR 1.43; 95% CI 1.23-1.67) were risk factors for failure. When considering revision for stiffness only, BMI 30-35 (p = 0.01, OR 3.27; 95% CI 1.41-7.61), lower pre-MUA flexion (p < 0.01, OR 1.43; 95% CI 1.18-1.75), and history of prior knee surgery (p = 0.04, OR 2.31; 95% CI 1.06-5.04) were predictors of failure. Time to MUA (p = 0.48), thromboprophylaxis (p = 0.44), pre-operative opioid use (p = 0.34), depression/anxiety (p = 1.0), and several other factors analyzed were not associated with failure. CONCLUSION: In this large cohort, elevated BMI and lower pre-MUA flexion were risk factors for failure of MUA. History of prior knee surgery was an additional predictor of requiring revision for stiffness.

Genome-wide screen of Mycobacterium tuberculosis- infected macrophages identified the GID/CTLH complex as a determinant of intracellular bacterial growth.

The eukaryotic GID/CTLH complex is a highly conserved E3 ubiquitin ligase involved in a broad range of biological processes. However, a role of this complex in host antimicrobial defenses has not been described. We exploited Mycobacterium tuberculosis ( Mtb ) induced cytotoxicity in macrophages in a FACS based CRISPR genetic screen to identify host determinants of intracellular Mtb growth restriction. Our screen identified 5 ( GID8 , YPEL5 , WDR26 , UBE2H , MAEA ) of the 10 predicted members of the GID/CTLH complex as determinants of intracellular growth of both Mtb and Salmonella serovar Typhimurium. We show that the antimicrobial properties of the GID/CTLH complex knockdown macrophages are mediated by enhanced GABAergic signaling, activated AMPK, increased autophagic flux and resistance to cell death. Meanwhile, Mtb isolated from GID/CTLH knockdown macrophages are nutritionally starved and oxidatively stressed. Our study identifies the GID/CTLH complex activity as broadly suppressive of host antimicrobial responses against intracellular bacterial infections.

The Wagner Cone Stem for Atypical Femoral Anatomy in Total Hip Arthroplasty: A Report of 320 Cases with Minimum 5-Year Follow-up.

BACKGROUND: The Wagner Cone Prosthesis was designed to address complex femoral deformities during total hip arthroplasty (THA), but its mid-term component survivorship and functional outcomes remain undetermined. The objectives of this study were to determine the implant survivorship, patient satisfaction, functional outcomes, osseointegration as seen radiographically, implant subsidence, and complications of THA using the Wagner Cone Prosthesis stem at intermediate-term follow-up. METHODS: This study involved 302 patients with proximal femoral deformities, including developmental hip dysplasia and Legg-Calvé-Perthes disease, who underwent a total of 320 primary THAs using the Wagner Cone Prosthesis. The average age at the time of surgery was 49.4 ± 14.5 years (range, 18.8 to 85.6 years). Patient satisfaction was recorded using a self-administered questionnaire assessing satisfaction in 4 domains. The University of California at Los Angeles (UCLA) activity score, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Oxford Hip Score (OHS), the Forgotten Joint Score (FJS), radiographic outcomes, and complications were recorded. The mean follow-up time was 10.1 years (range, 5.2 to 15.5 years). RESULTS: Survivorship of the Wagner Cone Prosthesis was 98.7% (95% confidence interval [CI]: 97.2% to 100%) with stem revision as the end point and 95.8% (95% CI: 93.5% to 98.2%) with reoperation for any reason as the end point at 10 years postoperatively. In total, 3 stems were revised: 2 for infection and 1 for chronic hip dislocation. The median patient satisfaction score was 95 (interquartile range [IQR], 80 to 100), median UCLA score was 6 (IQR, 6 to 7), median WOMAC score was 18 (IQR, 16 to 22), median OHS was 40 (IQR, 36 to 47), and median FJS was 80 (IQR, 76 to 88) at the time of final follow-up. All Wagner Cone stems that were not revised showed radiographic evidence of osseointegration, with a mean stem subsidence of 0.9 ± 0.8 mm at the most recent follow-up. CONCLUSIONS: The use of the Wagner Cone Prosthesis stem in patients with complex femoral anatomy undergoing primary THA is associated with excellent component survivorship, high levels of patient satisfaction, good functional outcomes, and reliable osseointegration with minimal stem subsidence as seen on radiographs at intermediate-term follow-up. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Long-term outcomes of revision total hip arthroplasty with the Zimmer Modular Revision hip system.

Aims: There are limited long-term studies reporting on outcomes of the Zimmer Modular Revision (ZMR) stem, and concerns remain regarding failure. Our primary aim was to determine long-term survival free from all-cause revision and stem-related failure for this modular revision stem in revision total hip arthroplasty (THA). Secondary aims included evaluating radiological and functional outcomes. Methods: We retrospectively identified all patients in our institutional database who underwent revision THA using the ZMR system from January 2000 to December 2007. We included 106 patients (108 hips) with a mean follow-up of 14.5 years (2.3 to 22.3). Mean patient age was 69.2 years (37.0 to 89.4), and 51.9% were female (n = 55). Indications for index revision included aseptic loosening (73.1%), infection (16.7%), fracture (9.3%), and stem fracture (0.9%). Kaplan-Meier analysis was used to determine the all-cause and stem-related failure revision-free survival. At most recent follow-up, Oxford Hip Scores (OHS) were collected, and radiological stem stability was determined using the Engh classification. Results: A total of 17 hips (15.7%) underwent re-revision of any component. Indications for re-revision were stem failure (35.3%; n = 6), infection (29.4%; n = 5), instability (29.4%; n = 5), and acetabular aseptic loosening (5.9%; n = 1). The five- and 15-year all-cause survival was 89.7% (95% confidence interval (CI) 86.7 to 92.7) and 83.3% (95% CI 79.6 to 87.0), respectively. There were six re-revisions (5.6%) for stem failure; five for stem fracture and one for aseptic loosening. The five- and 15-year survival free from stem-related failure was 97.2% (95% CI 95.6 to 98.8) and 94.0% (95% CI 91.6 to 96.4), respectively. At final follow-up, the mean OHS was 36.9 (8.0 to 48.0) and 95.7% (n = 66) of surviving modular revision stems were well-fixed in available radiographs. Conclusion: Femoral revision with the ZMR offers satisfactory long-term all-cause revision-free survival, good survival free of stem-related failure, and favourable clinical outcomes. Stem fracture was the most common reason for stem-related failure and occurred both early and late. This highlights the importance of both early and long-term surveillance for stem-related failure.

Porous Tantalum Metaphyseal Cones for Severe Femoral and Tibial Bone Defects in Revision Total Knee Arthroplasty are Reliable for Fixation at Mean 5-Year Follow-Up.

BACKGROUND: Porous tantalum metaphyseal cones may facilitate reconstructions of severe bone defects during revision total knee arthroplasty (TKA), but there remains a paucity of data on their outcomes at mean 5 years of follow-up. This study reports the component survivorship, patient satisfaction, functional outcomes, radiographic osseointegration, and complications of revision TKA with porous tantalum metaphyseal cones at mid-term (mean 5-year) follow-up. METHODS: This study included 152 patients who had a mean age of 66 years (range, 33 to 86 years) undergoing revision TKA with porous tantalum metaphyseal cones. Indications for surgery included aseptic loosening (n = 87, 57.3%), second-stage reimplantation for infection (n = 42, 27.6%), osteolysis with well-fixed components (n = 20, 13.2%), and periprosthetic fracture (n = 3, 2.0%). Component survivorship, clinical outcomes, radiographic outcomes, and any complications were recorded. The mean follow-up time was 5.6 years (range, 2.2 to 13.7). RESULTS: Survivorship was 100% when the end point was revision of the metaphyseal cone (no cones were revised) and 83.8% (95% confidence interval: 77.9 to 90.2%) when the end point was reoperation for any reason at 5-year follow-up. Reoperations were performed for infection (n = 10), instability (n = 4), periprosthetic fracture (n = 2), and quadriceps rupture/dehiscence (n = 3). The mean patient satisfaction score was 78.8 ± 11.3 and the mean Forgotten Joint Score was 62.2 ± 16.7 at the final follow-up. The preoperative median University of California at Los Angeles score improved from 2 (interquartile range 2 to 3) to 6 points (interquartile range 5 to 6) (P < .001), and the preoperative Oxford knee score improved from 15.2 ± 3.8 to 39.4 ± 5.1 points (P < .001) at the final follow-up. All metaphyseal cones showed radiographic evidence of osteointegration without any subsidence or loosening. CONCLUSIONS: Porous tantalum metaphyseal cones enabled robust reconstructions of severe femoral and tibial bone defects during revision TKA. These reconstructions were associated with excellent survivorship, improvements in functional outcomes, and reproducible radiographic osseointegration at mean 5-year follow-up. The most common reasons for reoperation were infection and instability.

Clinical Outcomes and Risk Factors for Re-Revision Due to Trunnion Corrosion in Primary Metal-on-Polyethylene Total Hip Arthroplasty.

BACKGROUND: There is a paucity of literature regarding the mid-term (greater than 2 years) outcomes of revision for adverse local tissue reaction to metal debris due to corrosion at the head-neck junction (trunnionosis) in metal-on-polyethylene total hip arthroplasty (THA), and risk factors for re-revision remain largely unknown. We aimed to report the re-revision-free survival and functional outcomes for this patient population and to identify risk factors for re-revision. METHODS: A total of 80 hips (79 patients) with a metal-on-polyethylene THA who had undergone revision for trunnionosis at our institution were included. The mean study follow-up from index trunnionosis revision was 4.6 years (range, 2.0 to 9.4). Kaplan-Meier survival analysis was performed with all-cause re-revision as the end point, and multivariate logistic regression was used to identify risk factors for re-revision. RESULTS: We saw that twenty-one hips (26%) underwent re-revision at a mean of 8.0 months (range, 0.03 to 36.3) after the index trunnionosis revision, most commonly for instability and infection. The two- and five-year all-cause re-revision-free survival rates were 75.0 and 73.2%, respectively. The mean Oxford Hip Score was 33.7 (range, 11 to 48); 76% were satisfied, and 24% were dissatisfied with their hip. Multivariate analysis identified not undergoing a cup revision (odds ratio: 4.5; 95% confidence interval: 1.03 to 19.7) and time from primary THA to the index trunnionosis revision (odds ratio: 0.77; 95% confidence interval: 0.62 to 0.97) as risk factors for undergoing re-revision. CONCLUSIONS: The risk of early re-revision for these patients is high (26%), mostly due to infection and instability, and functional outcomes are fair. Not performing a cup revision appears to be a risk factor for re-revision, as is the shorter time from primary THA to trunnionosis revision. LEVEL OF EVIDENCE: III.

Avaliação do erro nas coordenadas de localização estereotática guiada por tomografia computadorizada do encéfalo / CT-guided stereotactic localization for brain lesions. An evaluation of the error in the acquisition and calculation of the coordinates

São analisados 106 procedimentos em pacientes submetidos à estereotomografia. Os procedimentos foram realizados para obtenção de biópsias cerebrais, orientação de craniotomias, colocação de cateter em cavidade tumoral, drenagem de hematoma e de abscesso intracerebrais. As orientações de craniotomia foram realizadas para localizar más-formações arteriovenosas, tumores e processos inflamatórios, em 21 pacientes. As biópsias cerebrais estereotáticas, realizadas em 82 casos para diagnóstico anatomopatológico, apresentaram índice de positividade de 87,5 por cento, com complicações em 1,2 por cento dos casos. São analisadas estatisticamente as variáveis, como: idade, sexo, procedimento realizado, diagnóstico anatomopatológico e volume das lesões. É discutida a imprecisão na aquisição e cálculo das coordenadas estereotáticas com a tomografia computadorizada do encéfalo e verificada a precisão do método estereotomográfico com a utilização de um phanton. O maior erro das coordenadas foi de 6,8 mm com cortes tomográficos axiais de 4 mm a 5 mm.