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Valosin-containing protein (VCP) is an AAA+ ATPase that plays critical roles in multiple ubiquitin-dependent cellular processes. Dominant pathogenic variants in VCP are associated with adult-onset multisystem proteinopathy (MSP), which manifests as myopathy, bone disease, dementia, and/or motor neuron disease. Through GeneMatcher, we identified 13 unrelated individuals who harbor heterozygous VCP variants (12 de novo and 1 inherited) associated with a childhood-onset disorder characterized by developmental delay, intellectual disability, hypotonia, and macrocephaly. Trio exome sequencing or a multigene panel identified nine missense variants, two in-frame deletions, one frameshift, and one splicing variant. We performed in vitro functional studies and in silico modeling to investigate the impact of these variants on protein function. In contrast to MSP variants, most missense variants had decreased ATPase activity, and one caused hyperactivation. Other variants were predicted to cause haploinsufficiency, suggesting a loss-of-function mechanism. This cohort expands the spectrum of VCP-related disease to include neurodevelopmental disease presenting in childhood.
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Enfermedades Musculares , Trastornos del Neurodesarrollo , Adulto , Humanos , Proteína que Contiene Valosina/genética , Hipotonía Muscular , Mutación Missense/genéticaRESUMEN
Adhesion to mucosal surfaces is a critical step in many bacterial and fungal infections. Here, using a mouse model of oral infection by the human fungal pathobiont Candida albicans, we report the identification of a novel regulator of C. albicans adhesion to the oral mucosa. The regulator is a member of the regulatory factor X (RFX) family of transcription factors, which control cellular processes ranging from genome integrity in model yeasts to tissue differentiation in vertebrates. Mice infected with the C. albicans rfx1 deletion mutant displayed increased fungal burden in tongues compared to animals infected with the reference strain. High-resolution imaging revealed RFX1 transcripts being expressed by C. albicans cells during infection. Concomitant with the increase in fungal burden, the rfx1 mutant elicited an enhanced innate immune response. Transcriptome analyses uncovered HWP1, a gene encoding an adhesion protein that mediates covalent attachment to buccal cells, as a major RFX1-regulated locus. Consistent with this result, we establish that C. albicans adhesion to oral cells is modulated by RFX1 in an HWP1-dependent manner. Our findings expand the repertoire of biological processes controlled by the RFX family and illustrate a mechanism whereby C. albicans can adjust adhesion to the oral epithelium.
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Candida albicans , Proteínas Fúngicas , Factor Regulador X1 , Animales , Humanos , Candida albicans/genética , Epitelio/microbiología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Mucosa Bucal/microbiología , Factor Regulador X1/genética , Factor Regulador X1/metabolismoRESUMEN
For the control of biofouling, some paints based on compounds that are toxic to marine organisms have been used. There is an intensive search for biodegradable solutions that are friendly to non-target organisms. Bacteria have been shown to be a source of compounds with antifouling potential. In this work, the antifouling activity of a strain of Staphylococcus aureus was evaluated. Extracts activity against biofilm-forming bacteria and the toxicity against Artemia franciscana were evaluated. The extracts were incorporated in a hard gel and a paint matrix, and they were exposed to the sea. In both the laboratory and field, we found that the compounds produced by S. aureus have antifouling activity. The non-toxicity of the tested extracts against Artemia franciscana nauplii suggests that the extracts obtained from S. aureus could have a low ecological impact over non-target organisms. Significant differences were found in the percentage of organisms cover in hard gels with extracts and control. After 90 days, important differences were also observed between the percentage of organisms cover of the paints that contained extracts and the control. Dichloromethane extract is the most effective for the inhibition or delay of the settlement of organisms For this reason, they could be used in matrices with different applications, such as in the shipping industry, aquaculture, or any other in which biofouling is a cause of inconvenience.
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Incrustaciones Biológicas , Incrustaciones Biológicas/prevención & control , Staphylococcus aureus , Biopelículas , PinturaRESUMEN
OBJECTIVE: Neurobehavioral dysregulation (NBD), a core clinical feature of traumatic encephalopathy syndrome, encompasses neuropsychiatric symptoms reported among individuals with a history of repetitive head impact exposure, including contact sport athletes. The objective of this study was to examine the construct and subconstructs of NBD through a series of factor and cluster analyses. METHODS: Six clinician-scientists selected self-report questionnaire items relevant to NBD from seven available neuropsychiatric scales through a blinded voting process. These items were subjected to confirmatory factor analyses in a sample of 178 former college and professional American football players and 60 asymptomatic individuals without a history of repetitive head impact exposure. All participants were enrolled in the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project. Factor scores were generated on the basis of the optimal expert-informed model for NBD. Construct validity was assessed with neuropsychiatric scales not included in generation of the factor scores. Cluster analyses with NBD factor scores were used to examine symptom profiles. RESULTS: Factor analyses confirmed that NBD was composed of four subconstructs: explosivity, emotional dyscontrol, impulsivity, and affective lability. Cluster analyses indicated four distinct symptom profiles of NBD in this group of former football players: asymptomatic (N=80, 45%), short fuse (N=33, 19%), high affective lability (N=34, 19%), and high NBD (N=31, 17%). CONCLUSIONS: These findings characterize NBD as a multifaceted clinical construct with a heterogeneous presentation, providing a foundation for empirical work on the diagnostic criteria for traumatic encephalopathy syndrome and research on the neurobiological underpinnings of NBD.
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Isolated optic nerve (ON) relapse is a rare occurrence in lymphoblastic leukemia (LBL). A 10-year-old boy with T-LBL presented 8 months after diagnosis with blurred vision and thickening of right ON on magnetic resonance imaging consistent with relapse. Cerebrospinal fluid and bone marrow were negative for leukemia. He received reinduction chemotherapy (including nelarabine and craniospinal radiation) followed by a myeloablative matched sibling donor bone marrow transplant. He remains in remission 2 years post-transplant with normal vision. We also review the literature for reports of isolated ON relapse in patients with LBL. Our patient's clinical course demonstrates that disease control can be achieved with early detection of ON relapse before disease progression.
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Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Masculino , Niño , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Trasplante de Médula Ósea , Nervio Óptico/patología , Nervio Óptico/diagnóstico por imagen , Recurrencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/diagnósticoRESUMEN
OBJECTIVE: To describe the MR features enabling prenatal diagnosis of pontocerebellar hypoplasia (PCH). METHOD: This was a retrospective single monocentre study. The inclusion criteria were decreased cerebellar biometry on dedicated neurosonography and available fetal Magnetic Resonance Imaging (MRI) with PCH diagnosis later confirmed either genetically or clinically on post-natal MRI or by autopsy. The exclusion criteria were non-available MRI and sonographic features suggestive of a known genetic or other pathologic diagnosis. The collected data were biometric or morphological imaging parameters, clinical outcome, termination of pregnancy (TOP), pathological findings and genetic analysis (karyotyping, chromosomal microarray, DNA sequencing targeted or exome). PCH was classified as classic, non-classic, chromosomal, or unknown type. RESULTS: Forty-two fetuses were diagnosed with PCH, of which 27 were referred for decreased transverse cerebellar diameter at screening ultrasound. Neurosonography and fetal MRI were performed at a mean gestational age of 29 + 4 and 31 + 0 weeks, respectively. Termination of pregnancy occurred. Pregnancy was terminated in 24 cases. Neuropathological examination confirmed the diagnosis in 24 cases and genetic testing identified abnormalities in 29 cases (28 families, 14 chromosomal anomaly). Classic PCH is associated with pontine atrophy and small MR measurements decreasing with advancing gestation. CONCLUSION: This is the first large series of prenatally diagnosed PCHs. Our study shows the essential contribution of fetal MRI to the prenatal diagnosis of PCH. Classic PCHs are particularly severe and are associated with certain MR features.
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Enfermedades Cerebelosas , Imagen por Resonancia Magnética , Diagnóstico Prenatal , Embarazo , Femenino , Humanos , Lactante , Estudios Retrospectivos , Estudios de Seguimiento , Diagnóstico Prenatal/métodos , Imagen por Resonancia Magnética/métodos , Ultrasonografía Prenatal/métodosRESUMEN
BACKGROUND: The retinoic acid (RA) pathway plays a crucial role in both eye morphogenesis and the visual cycle. Individuals with monoallelic and biallelic pathogenic variants in retinol-binding protein 4 (RBP4), encoding a serum retinol-specific transporter, display variable ocular phenotypes. Although few families have been reported worldwide, recessive inherited variants appear to be associated with retinal degeneration, while individuals with dominantly inherited variants manifest ocular development anomalies, mainly microphthalmia, anophthalmia and coloboma (MAC). METHODS: We report here seven new families (13 patients) with isolated and syndromic MAC harbouring heterozygous RBP4 variants, of whom we performed biochemical analyses. RESULTS: For the first time, malformations that overlap the clinical spectrum of vitamin A deficiency are reported, providing a link with other RA disorders. Our data support two distinct phenotypes, depending on the nature and mode of inheritance of the variants: dominantly inherited, almost exclusively missense, associated with ocular malformations, in contrast to recessive, mainly truncating, associated with retinal degeneration. Moreover, we also confirm the skewed inheritance and impact of maternal RBP4 genotypes on phenotypical expression in dominant forms, suggesting that maternal RBP4 genetic status and content of diet during pregnancy may modify MAC occurrence and severity. Furthermore, we demonstrate that retinol-binding protein blood dosage in patients could provide a biological signature crucial for classifying RBP4 variants. Finally, we propose a novel hypothesis to explain the mechanisms underlying the observed genotype-phenotype correlations in RBP4 mutational spectrum. CONCLUSION: Dominant missense variants in RBP4 are associated with MAC of incomplete penetrance with maternal inheritance through a likely dominant-negative mechanism.
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Anoftalmos , Microftalmía , Degeneración Retiniana , Embarazo , Femenino , Humanos , Degeneración Retiniana/genética , Degeneración Retiniana/patología , Microftalmía/genética , Anoftalmos/genética , Tretinoina/metabolismo , Proteínas de Unión al Retinol/genética , Proteínas Plasmáticas de Unión al Retinol/genética , Proteínas Plasmáticas de Unión al Retinol/química , Proteínas Plasmáticas de Unión al Retinol/metabolismoRESUMEN
PURPOSE: In this study, we describe the phenotype and genotype of the largest cohort of patients with Joubert syndrome (JS) carrying pathogenic variants on one of the most frequent causative genes, CC2D2A. METHODS: We selected 53 patients with pathogenic variants on CC2D2A, compiled and analysed their clinical, neuroimaging and genetic information and compared it to previous literature. RESULTS: Developmental delay (motor and language) was nearly constant but patients had normal intellectual efficiency in 74% of cases (20/27 patients) and 68% followed mainstream schooling despite learning difficulties. Epilepsy was found in only 13% of cases. Only three patients had kidney cysts, only three had genuine retinal dystrophy and no subject had liver fibrosis or polydactyly. Brain MRIs showed typical signs of JS with rare additional features. Genotype-phenotype correlation findings demonstrate a homozygous truncating variant p.Arg950* linked to a more severe phenotype. CONCLUSION: This study contradicts previous literature stating an association between CC2D2A-related JS and ventriculomegaly. Our study implies that CC2D2A-related JS is linked to positive neurodevelopmental outcome and low rate of other organ defects except for homozygous pathogenic variant p.Arg950*. This information will help modulate patient follow-up and provide families with accurate genetic counselling.
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Anomalías Múltiples , Anomalías del Ojo , Enfermedades Renales Quísticas , Humanos , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Enfermedades Renales Quísticas/diagnóstico , Enfermedades Renales Quísticas/genética , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Anomalías del Ojo/diagnóstico , Anomalías del Ojo/genética , Anomalías del Ojo/patología , Retina/diagnóstico por imagen , Retina/patología , Proteínas del CitoesqueletoRESUMEN
BACKGROUND: One important factor for the prevention of surgical site infections is ultraclean air in the operating room (OR). Still, the direct sterilization potential of most technologies, especially in a dynamic clinical setting, is not well understood. We aimed to determine and compare the microbial presence from the inlet and outlet flow of a filtration unit with crystalline ultraviolet-C (C-UVC) light. METHODS: A prospective study was conducted at a single institution, where primary total joint arthroplasty and spine surgeries were performed. The OR was fitted with a positive ventilation system. In addition, a filtration unit with a C-UVC sterilizing light was placed in the OR. The inlet and outlet air flows were swabbed simultaneously and compared. Swabs were processed for culture and next-generation sequencing. RESULTS: The mean length of the surgical procedures sampled was 68 ± 13 minutes. Overall, 19 out of 200 (9.5%) swabs isolated microorganisms. Inlet air swabs were positive at a higher rate (16 versus 3%; P < .01) compared to the outlet air swabs. A wide variety of Gram-positive, Gram-negative, and anaerobic bacteria were isolated, but fungi were only recovered from inlet air swabs. The detection of microorganisms was also higher when more door openings were performed (32.5 ± 7.1 versus 27.9 ± 5.6; P < .01). CONCLUSIONS: Air swabs mainly isolated microorganisms from the inlet flow to the filtration unit with a C-UVC light. The sterilizing unit counteracted factors affecting the air quality in the OR, namely door openings, surgical personnel, and tissue combustion.
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OBJECTIVE: determine the complications during the first year after liver transplantation in pediatric patients of the INSN-SB during the period 2016-2020. MATERIALS AND METHODS: Descriptive, cross-sectional study. The medical records of liver transplant patients seen during post-transplant follow-up at the INSN-SB were reviewed, collecting epidemiological characteristics, transplant indication; PELD score, CHILD score and complications prior to the transplant, as well as the frequency of the main complications presented during the first year after the transplant. RESULTS: Of the 16 patients evaluated, 62.5% were under 1 year of age, with a median weight of 7.4kg, 50% presented a CHILD C score, with a median PELD of 23, the main reason for transplantation was atresia of bile ducts (62.5%), the main complications prior to transplantation were portal hypertension (75%) and malnutrition (68.8%). All post-transplant patients presented at least one infectious complication: bacterial (53%), CMV infection (75%) and EBV infection (31%); Regarding vascular complications, 25% presented portal vein thrombosis and one patient (6%) presented hepatic artery stenosis; Regarding biliary complications, 12.5% presented biliary fistula, also 12.5% presented bile duct dilation, while 6.25% presented bilioma. CONCLUSIONS: Among the main complications of the post-liver transplant patient, we can highlight that all patients presented at least one infectious complication (100%), vascular complications in 31% and biliary complications in 31.25% of patients.
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Trasplante de Hígado , Complicaciones Posoperatorias , Humanos , Trasplante de Hígado/efectos adversos , Estudios Transversales , Masculino , Femenino , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Lactante , Perú , Preescolar , Niño , Centros de Atención Terciaria , Adolescente , Estudios RetrospectivosRESUMEN
The Rho-guanine nucleotide exchange factor (RhoGEF) TRIO acts as a key regulator of neuronal migration, axonal outgrowth, axon guidance, and synaptogenesis by activating the GTPase RAC1 and modulating actin cytoskeleton remodeling. Pathogenic variants in TRIO are associated with neurodevelopmental diseases, including intellectual disability (ID) and autism spectrum disorders (ASD). Here, we report the largest international cohort of 24 individuals with confirmed pathogenic missense or nonsense variants in TRIO. The nonsense mutations are spread along the TRIO sequence, and affected individuals show variable neurodevelopmental phenotypes. In contrast, missense variants cluster into two mutational hotspots in the TRIO sequence, one in the seventh spectrin repeat and one in the RAC1-activating GEFD1. Although all individuals in this cohort present with developmental delay and a neuro-behavioral phenotype, individuals with a pathogenic variant in the seventh spectrin repeat have a more severe ID associated with macrocephaly than do most individuals with GEFD1 variants, who display milder ID and microcephaly. Functional studies show that the spectrin and GEFD1 variants cause a TRIO-mediated hyper- or hypo-activation of RAC1, respectively, and we observe a striking correlation between RAC1 activation levels and the head size of the affected individuals. In addition, truncations in TRIO GEFD1 in the vertebrate model X. tropicalis induce defects that are concordant with the human phenotype. This work demonstrates distinct clinical and molecular disorders clustering in the GEFD1 and seventh spectrin repeat domains and highlights the importance of tight control of TRIO-RAC1 signaling in neuronal development.
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Factores de Intercambio de Guanina Nucleótido/genética , Mutación , Trastornos del Neurodesarrollo/genética , Proteínas Serina-Treonina Quinasas/genética , Proteína de Unión al GTP rac1/metabolismo , Secuencia de Aminoácidos , Estudios de Cohortes , Femenino , Factores de Intercambio de Guanina Nucleótido/química , Células HEK293 , Humanos , Masculino , Fenotipo , Proteínas Serina-Treonina Quinasas/química , Homología de Secuencia de AminoácidoRESUMEN
The success of precision medicine coupled with the disappointing impact of broad-spectrum antibiotic use on microbiome stability and bacterial resistance, has triggered a shift in antibiotic design strategies toward precision antibiotics. This also includes the implementation of novel vectorization approaches directed to improve the internalization of antibacterial agents into deadly gram-negative pathogens through precise and well-defined mechanisms. The conjugation of antibiotics to siderophores (iron scavengers), which are compounds that are able to afford stable iron-complexes that facilitate the internalization into the cell by using bacterial iron uptake pathways as gateways, is a strategy that has begun to show excellent results with the commercialization of the first antibiotic based on this principle, cefiderocol. This digests review provides an overview of the molecular basis for this antibiotic-siderophore conjugation approach, along with recent successful examples and highlights future challenges facing this booming research area.
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Antibacterianos , Infecciones Bacterianas , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Sideróforos/química , Sideróforos/metabolismo , Hierro/metabolismoRESUMEN
The endocannabinoid system is a highly conserved and ubiquitous signalling pathway with broad-ranging effects. Despite critical pathway functions, gene variants have not previously been conclusively linked to human disease. We identified nine children from eight families with heterozygous, de novo truncating variants in the last exon of DAGLA with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. All children displayed paroxysms of nystagmus or eye deviation accompanied by compensatory head posture and worsened incoordination most frequently after waking. RNA sequencing showed clear expression of the truncated transcript and no differences were found between mutant and wild-type DAGLA activity. Immunofluorescence staining of patient-derived fibroblasts and HEK cells expressing the mutant protein showed distinct perinuclear aggregation not detected in control samples. This report establishes truncating variants in the last DAGLA exon as the cause of a unique paediatric syndrome. Because enzymatic activity was preserved, the observed mislocalization of the truncated protein may account for the observed phenotype. Potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect. To our knowledge, this is the first report directly linking an endocannabinoid system component with human genetic disease and sets the stage for potential future therapeutic avenues.
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Endocannabinoides , Enfermedades del Sistema Nervioso , Humanos , Niño , Fenotipo , Enfermedades del Sistema Nervioso/genética , Heterocigoto , Síndrome , Proteínas MutantesRESUMEN
BACKGROUND: Cutibacterium acnes has been described as the most common causative microorganism in prosthetic shoulder infections. Conventional anaerobic culture or molecular-based technologies are usually used for this purpose, but little to no concordance between these methodologies (k = 0.333 or less) has been observed. QUESTIONS/PURPOSES: (1) Is the minimum C. acnes load for detection higher for next-generation sequencing (NGS) than for anaerobic conventional culture? (2) What duration of incubation is necessary for anaerobic culture to detect all C. acnes loads? METHODS: Five C. acnes strains were tested for this study: Four strains were causing infection and were isolated from surgical samples. Meanwhile, the other was a reference strain commonly used as a positive and quality control in microbiology and bioinformatics. To create inoculums with varying degrees of bacterial load, we began with a standard bacterial suspension at 1.5 x 10 8 colony-forming units (CFU)/mL and created six more diluted suspensions (from 1.5 x 10 6 CFU/mL to 1.5 x 10 1 CFU/mL). Briefly, to do so, we transferred 200 µL from the tube with the highest inoculum (for example, 1.5 x 10 6 CFU/mL) to the following dilution tube (1.5 x 10 5 CFU/mL; 1800 µL of diluent + 200 µL of 1.5 x 10 6 CFU/mL). We serially continued the transfers to create all diluted suspensions. Six tubes were prepared per strain. Thirty bacterial suspensions were tested per assay. Then, 100 µL of each diluted suspension was inoculated into brain heart infusion agar with horse blood and taurocholate agar plates. Two plates were used per bacterial suspension in each assay. All plates were incubated at 37°C in an anaerobic chamber and assessed for growth after 3 days of incubation and daily thereafter until positive or Day 14. The remaining volume of each bacterial suspension was sent for NGS analysis to identify bacterial DNA copies. We performed the experimental assays in duplicate. We calculated mean DNA copies and CFUs for each strain, bacterial load, and incubation timepoint assessed. We reported detection by NGS and culture as a qualitative variable based on the identification or absence of DNA copies and CFUs, respectively. In this way, we identified the minimum bacterial load detected by NGS and culture, regardless of incubation time. We performed a qualitative comparison of detection rates between methodologies. Simultaneously, we tracked C. acnes growth on agar plates and determined the minimum incubation time in days required for CFU detection in all strains and loads examined in this study. Growth detection and bacterial CFU counting were performed by three laboratory personnel, with a high intraobserver and interobserver agreement (κ > 0.80). A two-tailed p value below 0.05 was considered statistically significant. RESULTS: Conventional cultures can detect C. acnes at a load of 1.5 x 10 1 CFU/mL, whereas NGS can detect bacteria when the concentration was higher, at 1.5 x 10 2 CFU/mL. This is represented by a lower positive detection proportion (73% [22 of 30]) for NGS than for cultures (100% [30 of 30]); p = 0.004). By 7 days, anaerobic cultures were able to detect all C. acnes loads, even at the lowest concentrations. CONCLUSION: When NGS is negative and culture is positive for C. acnes , there is likely a low bacterial load. Holding cultures beyond 7 days is likely unnecessary. CLINICAL RELEVANCE: This is important for treating physicians to decide whether low bacterial loads necessitate aggressive antibiotic treatment or whether they are more likely contaminants. Cultures that are positive beyond 7 days likely represent contamination or bacterial loads even below the dilution used in this study. Physicians may benefit from studies designed to clarify the clinical importance of the low bacteria loads used in this study at which both methodologies' detection differed. Moreover, researchers might explore whether even lower C. acnes loads have a role in true periprosthetic joint infection.
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Bacterias , Propionibacterium acnes , Animales , Caballos , Agar , Anaerobiosis , Propionibacterium acnes/genética , Secuenciación de Nucleótidos de Alto Rendimiento , ADNRESUMEN
BACKGROUND: One of the important factors for surgical site infection prevention is the implementation of an ultraclean operating room. This study was designed to evaluate back-table sterility during total joint arthroplasty. METHODS: This prospective study includes 52 patients undergoing primary total joint arthroplasty between November 2021 and January 2022. A total of 4 swabs (2 air swabs and 2 table swabs) were obtained for each case, at the conclusion of surgery and prior to the takedown of drapes. One swab from each set was sent for culture, and the other was sent for next-generation sequencing (NGS) analysis. RESULTS: Among 104 back-table swabs, a total of 13 (12.5%) organisms were isolated. Of these, 7 organisms were isolated by culture and 6 by NGS. No microorganisms were isolated by both culture and NGS from back-table swabs. Among 104 air swabs, a total of 11 (10.6%) organisms were isolated. Of these, 6 microorganisms were isolated by culture and 5 by NGS. In 4 of the 104 swabs, both culture- and NGS-isolated organisms were from air swabs. Of the 104 (12.5%) back-table and air swabs, 13 were culture positive. While more than 1 pathogen was identified in 2 air swabs, all back-table swabs were monomicrobial by culture. Pathogens were identified from 11 of 104 (10.6%) swabs by NGS, while more than 1 pathogen was identified in 4 swabs (2 air and 2 back table). CONCLUSION: The findings of this study raise an important issue that the surgical field including the sterile table setup for instruments is not "sterile" and can harbor pathogens.
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Infertilidad , Quirófanos , Humanos , Estudios Prospectivos , ArtroplastiaRESUMEN
BACKGROUND: Two-stage exchange arthroplasty remains the preferred surgical treatment for chronic periprosthetic joint infection. Currently, there is no single reliable marker to determine the optimal timing for reimplantation. The purpose of this prospective study was to assess the diagnostic utility of plasma D-dimer and other serological markers in predicting successful control of infection following reimplantation. METHODS: This study enrolled 136 patients undergoing reimplantation arthroplasty between November 2016 and December 2020. Strict inclusion criteria were applied including the need for a two-week "antibiotic holiday" prior to reimplantation. A total of 114 patients were included in the final analysis. Plasma D-dimer, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen were measured preoperatively. Treatment success was defined using the Musculoskeletal Infection Society Outcome-Reporting Tool. Receiver operating characteristic curves were used to assess the prognostic accuracy of each biomarker in predicting failure following reimplantation at a minimum 1-year follow-up. RESULTS: Treatment failure occurred in 33 patients (28.9%) at a mean follow-up of 3.2 years (range, 1.0 to 5.7). Median plasma D-dimer was significantly higher in the treatment failure group (1,604 versus 631 ng/mL, P < .001), whereas median CRP, ESR, and fibrinogen were not significantly different between the success and failure groups. Plasma D-dimer demonstrated the best diagnostic utility (area under the curve [AUC] 0.724, sensitivity 51.5%, specificity 92.6%), outperforming ESR (AUC 0.565, sensitivity 93.3%, specificity 22.5%), CRP (AUC 0.541, sensitivity 87.5%, specificity 26.3%), and fibrinogen (AUC 0.485, sensitivity 30.4%, specificity 80.0%). Plasma D-dimer level of ≥1,604 ng/mL was identified as the optimal cutoff that predicted failure following reimplantation. CONCLUSION: Plasma D-dimer was superior to serum ESR, CRP, and fibrinogen in predicting failure after the second stage of a two-stage exchange arthroplasty for periprosthetic joint infection. Based on the findings of this prospective study, plasma D-dimer may be a promising marker in assessing the control of infection in patients undergoing reimplantation surgery. LEVEL OF EVIDENCE: Level II.
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Artritis Infecciosa , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo , Hemostáticos , Infecciones Relacionadas con Prótesis , Humanos , Estudios Prospectivos , Infecciones Relacionadas con Prótesis/diagnóstico , Infecciones Relacionadas con Prótesis/cirugía , Reimplantación , Fibrinógeno , Sedimentación Sanguínea , Proteína C-Reactiva , Biomarcadores , Artroplastia de Reemplazo de Cadera/efectos adversos , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Pathogens causing prosthetic joint infection (PJI) are thought to gain access to the knee during surgery or from a remote site in the body. Recent studies have shown that there is a distinct microbiome in various sites of the body. This prospective study, and first of its kind, was set up to investigate the presence of possible microbiome in human knee and compare the profile in different knee conditions. METHODS: We obtained synovial fluid from 65 knees (55 patients) with various conditions that included normal knee, osteoarthritis (OA), aseptic revision, and those undergoing revision for PJI. The contralateral knee of patients who had a PJI were also aspirated for comparison. A minimum of 3 milliliters of synovial fluid was collected per joint. All samples were aliquoted for culture and next-generation sequencing analysis. RESULTS: The highest number of species was found in native osteoarthritic knees (P ≤ .035). Cutibacterium, Staphylococcus, and Paracoccus species were dominant in native nonosteoarthritic knees, and meanwhile a markedly high abundance of Proteobacteria was observed in the osteoarthritic joints. Moreover, the contralateral and aseptic revision knees showed a similar trend in bacterial composition (P = .75). The sequencing analysis of patients who had PJI diagnosis, confirmed the culture results. CONCLUSION: Distinct knee microbiome profiles can be detected in patients who have OA and other knee conditions. The distinct microbiome in the knee joint and the close host-microbe relationships within the knee joint may play a decisive role in the development of OA and PJI.
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Artritis Infecciosa , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Distinciones y Premios , Infecciones Relacionadas con Prótesis , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/métodos , Estudios Prospectivos , Infecciones Relacionadas con Prótesis/etiología , Articulación de la Rodilla/cirugía , Artritis Infecciosa/etiología , Reoperación/efectos adversos , Estudios Retrospectivos , Artroplastia de Reemplazo de Cadera/efectos adversosRESUMEN
The AgingPLUS program targets motivational barriers, including negative views of aging, as mechanisms to increase adult physical activity. A pilot study was conducted to test the efficacy of this new program against a generic successful aging program. Fifty-six participants were randomly assigned to the AgingPLUS group, and 60 participants were assigned to the active control group. Repeated-measures multivariate analyses of variance assessed changes in views of aging, physical activity, blood pressure, and hand-grip strength from pretest (Week 0) to delayed posttest (Week 8). The Condition × Occasion interactions were nonsignificant; however, significant main effects for condition and occasion were found. Follow-up tests showed that views of aging were more positive, and physical activity had significantly increased at Week 8 for all participants. In addition, in the treatment group, elevated blood pressure had significantly decreased and hand-grip strength had significantly increased at Week 8. Despite the nonsignificant multivariate findings, the main effect findings provided partial support for the efficacy of the AgingPLUS program.
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Envejecimiento , Ejercicio Físico , Humanos , Proyectos Piloto , Envejecimiento/fisiología , Fuerza de la ManoRESUMEN
Background: Diagnosis of pulmonary embolism (PE) constitutes a challenge for practitioners. Current practice involves use of pre-test probability prediction rules. Several strategies to optimize this process have been explored. Objectives: To explore whether application of the pulmonary embolism rule-out criteria (PERC rule) and age-adjusted D-dimer (DD) would have reduced the number of computed tomography pulmonary angiography (CTPA) examinations performed in patients with suspected PE. Methods: A retrospective cross-sectional study of adult patients taken for CTPA under suspicion of PE in 2018 and 2020. The PERC rule and age-adjusted DD were applied. The number of cases without indications for imaging studies was estimated and the operational characteristics for diagnosis of PE were calculated. Results: 302 patients were included. PE was diagnosed in 29.8%. Only 27.2% of 'not probable' cases according to the Wells criteria had D-dimer assays. Age adjustment would have reduced tomography use by 11.1%, with an AUC of 0.5. The PERC rule would have reduced use by 7%, with an AUC of 0.72. Conclusions: Application of age-adjusted D-dimer and the PERC rule to patients taken for CTPA because of suspected PE seems to reduce the number of indications for the procedure.
Contexto: O diagnóstico de embolia pulmonar (EP) representa um desafio para o profissional. A prática atual envolve o uso de modelos de previsão de probabilidade pré-teste e, para otimizar esse processo, várias estratégias têm sido exploradas. Objetivos: Investigar se a aplicação dos critérios de exclusão de EP (pulmonary embolism rule-out criteria, PERC) e do D-dímero (DD) ajustado para idade diminui o número de angiografias computadorizadas (ATCs) pulmonares realizadas em pacientes com suspeita de EP. Métodos: Estudo transversal retrospectivo com pacientes adultos submetidos a ATC pulmonar com suspeita de EP em 2018 e 2020. Foram aplicados os critérios PERC e o DD ajustado para idade. Foi estimado o número de casos não indicados para exames de imagem, e foram calculadas as características operacionais para o diagnóstico de EP. Resultados: Foram incluídos 302 pacientes, dos quais 29,8% apresentaram diagnóstico de EP. Apenas 27,2% dos casos não prováveis ââde acordo com os critérios de Wells apresentaram DD; o ajuste implicou em uma diminuição de ACTs de 11,1%, com área sob a curva de 0,5. Os critérios PERC diminuiriam em 7%, com área sob a curva de 0,72. Conclusões: A aplicação do DD ajustado para idade e dos critérios PERC em pacientes submetidos a ATC pulmonar por suspeita de EP parece diminuir a indicação para tais exames.
RESUMEN
HLA is a polymorphic antigen presenter which has provided valuable information on the susceptibility of populations to viruses. Therefore, the study of HLA can reveal specific susceptibility or resistance alleles to severe COVID-19 in an ethnically dependent manner. This pilot study investigated HLA alleles associated with COVID-19 severity in Tapachula, Chiapas, Mexico. A total of 146 Mexican Mestizos were typed for HLA class I and II using PCR-SSP. The patients were classified according to the outcome (death or improvement) and the infection's severity (mild or severe). In addition, a group of exposed uninfected individuals was included. HLA-A*68 was found to be a protective allele against the severe infection and fatal outcome; pC = 0.03, OR = 0.4, 95% CI =0.20-0.86, and pC =0.009, OR = 0.3, 95% CI =0.13-0.71 respectively. HLA-DRB1*03 also appears to be a protective factor against fatal outcome pC = 0.009, OR = 0.1, 95%IC = 0.01-0.66; however, the low frequency of this allele in the studied population limits the statistical power. The severity and fatal outcome of COVID-19 patients in Tapachula, Chiapas depend more on the lack of resistance than susceptibility HLA alleles.