The MELD Score Is Superior to the Maddrey Discriminant Function Score to Predict Short-Term Mortality in Alcohol-Associated Hepatitis: A Global Study.

INTRODUCTION: Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction. METHODS: Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days. RESULTS: In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years, interquartile range 40.9-55.0 years). The median MELD score was 23.5 (interquartile range 20.5-27.8). Mortality at 28 and 90 days was 20% and 30.9%, respectively. The area under the receiver operating characteristic curve for 28-day mortality ranged from 0.776 for MELD-sodium to 0.701 for mDF, and for 90-day mortality, it ranged from 0.773 for MELD to 0.709 for mDF. The area under the receiver operating characteristic curve for mDF to predict death was significantly lower than all other scores. Age added to MELD obtained only a small improvement of AUC. DISCUSSION: These results suggest that the mDF score should no longer be used to assess AH's prognosis. The MELD score has the best performance in predicting short-term mortality.

Liver Stiffness at the Time of Sustained Virological Response Predicts the Clinical Outcome in People Living With Human Immunodeficiency Virus and Hepatitis C Virus With Advanced Fibrosis Treated With Direct-acting Antivirals.

BACKGROUND: Some people living with hepatitis C virus (HCV) with sustained virological response (SVR) develop hepatic complications. Liver stiffness (LS) predicts clinical outcome in people living with human immunodeficiency virus (HIV) with active HCV coinfection, but information after SVR is lacking. We aimed to analyze the predictive ability of LS at SVR for liver complications in people living with HIV/HCV with advanced fibrosis treated with direct-acting antivirals (DAA). METHODS: In sum, 640 people living with HIV/HCV fulfilling the following criteria were included: (i) Achieved SVR with DAA-including regimen; (ii) LS ≥ 9.5 kPa before therapy; and (iii) LS measurement available at SVR. The primary endpoint was the occurrence of a liver complication-hepatic decompensation or hepatocellular carcinoma (HCC)-or requiring liver transplant after SVR. RESULTS: During a median (Q1-Q3) follow-up of 31.6 (22.7-36.6) months, 19 (3%) patients reached the primary endpoint. In the multivariate analysis, variables (subhazard ratio [SHR] [95% confidence interval]) associated with developing clinical outcomes were: prior hepatic decompensations (3.42 [1.28-9.12]), pretreatment CPT class B or C (62.5 [3.08-1246.42]) and MELD scores (1.37 [1.03-1.82]), CPT class B or C at SVR (10.71 [1.32-87.01]), CD4 cell counts <200/µL at SVR time-point (4.42 [1.49-13.15]), FIB-4 index at SVR (1.39 [1.13-1.70]), and LS at SVR (1.05 [1.02-1.08] for 1 kPa increase). None of the 374 patients with LS <14kPa at SVR time-point developed a liver complication or required hepatic transplant. CONCLUSIONS: LS at the time of SVR after DAA therapy predicts the clinical outcome of people living with HIV/HCV with advanced fibrosis. These results suggest that LS measurement may be helpful to select candidates to be withdrawn from surveillance programs.

Structural Glycoprotein E2 of Classical Swine Fever Virus Interacts with Host Protein Dynactin Subunit 6 (DCTN6) during the Virus Infectious Cycle.

The E2 protein in classical swine fever (CSF) virus (CSFV) is the major virus structural glycoprotein and is an essential component of the viral particle. E2 has been shown to be involved in several functions, including virus adsorption, induction of protective immunity, and virulence in swine. Using the yeast two-hybrid system, we previously identified a swine host protein, dynactin subunit 6 (DCTN6) (a component of the cell dynactin complex), as a specific binding partner for E2. We confirmed the interaction between DCTN6 and E2 proteins in CSFV-infected swine cells by using two additional independent methodologies, i.e., coimmunoprecipitation and proximity ligation assays. E2 residues critical for mediating the protein-protein interaction with DCTN6 were mapped by a reverse yeast two-hybrid approach using a randomly mutated E2 library. A recombinant CSFV mutant, E2ΔDCTN6v, harboring specific substitutions in those critical residues was developed to assess the importance of the E2-DCTN6 protein-protein interaction for virus replication and virulence in swine. CSFV E2ΔDCTN6v showed reduced replication, compared with the parental virus, in an established swine cell line (SK6) and in primary swine macrophage cultures. Remarkably, animals infected with CSFV E2ΔDCTN6v remained clinically normal during the 21-day observation period, which suggests that the ability of CSFV E2 to bind host DCTN6 protein efficiently during infection may play a role in viral virulence.IMPORTANCE Structural glycoprotein E2 is an important component of CSFV due to its involvement in many virus activities, particularly virus-host interactions. Here, we present the description and characterization of the protein-protein interaction between E2 and the swine host protein DCTN6 during virus infection. The E2 amino acid residues mediating the interaction with DCTN6 were also identified. A recombinant CSFV harboring mutations disrupting the E2-DCTN6 interaction was created. The effect of disrupting the E2-DCTN6 protein-protein interaction was studied using reverse genetics. It was shown that the same amino acid substitutions that abrogated the E2-DCTN6 interaction in vitro constituted a critical factor in viral virulence in the natural host, domestic swine. This highlights the potential importance of the E2-DCTN6 protein-protein interaction in CSFV virulence and provides possible mechanisms of virus attenuation for the development of improved CSF vaccines.

Molecular Characterization of the Viroporin Function of Foot-and-Mouth Disease Virus Nonstructural Protein 2B.

Nonstructural protein 2B of foot-and-mouth disease (FMD) virus (FMDV) is comprised of a small, hydrophobic, 154-amino-acid protein. Structure-function analyses demonstrated that FMDV 2B is an ion channel-forming protein. Infrared spectroscopy measurements using partially overlapping peptides that spanned regions between amino acids 28 and 147 demonstrated the adoption of helical conformations in two putative transmembrane regions between residues 60 and 78 and between residues 119 and 147 and a third transmembrane region between residues 79 and 106, adopting a mainly extended structure. Using synthetic peptides, ion channel activity measurements in planar lipid bilayers and imaging of single giant unilamellar vesicles (GUVs) revealed the existence of two sequences endowed with membrane-porating activity: one spanning FMDV 2B residues 55 to 82 and the other spanning the C-terminal region of 2B from residues 99 to 147. Mapping the latter sequence identified residues 119 to 147 as being responsible for the activity. Experiments to assess the degree of insertion of the synthetic peptides in bilayers and the inclination angle adopted by each peptide regarding the membrane plane normal confirm that residues 55 to 82 and 119 to 147 of 2B actively insert as transmembrane helices. Using reverse genetics, a panel of 13 FMD recombinant mutant viruses was designed, which harbored nonconservative as well as alanine substitutions in critical amino acid residues in the area between amino acid residues 28 and 147. Alterations to any of these structures interfered with pore channel activity and the capacity of the protein to permeabilize the endoplasmic reticulum (ER) to calcium and were lethal for virus replication. Thus, FMDV 2B emerges as the first member of the viroporin family containing two distinct pore domains.IMPORTANCE FMDV nonstructural protein 2B is able to insert itself into cellular membranes to form a pore. This pore allows the passage of ions and small molecules through the membrane. In this study, we were able to show that both current and small molecules are able to pass though the pore made by 2B. We also discovered for the first time a virus with a pore-forming protein that contains two independent functional pores. By making mutations in our infectious clone of FMDV, we determined that mutations in either pore resulted in nonviable virus. This suggests that both pore-forming functions are independently required during FMDV infection.

Effectiveness and safety of sofosbuvir-based regimens plus an NS5A inhibitor for patients with HCV genotype 3 infection and cirrhosis. Results of a multicenter real-life cohort.

Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014-October 2015). In total, 208 patients were included: 98 (47%) treatment-experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events.

Uncommon aetiological agents of catheter-related bloodstream infections.

The clinical and microbiological characteristics of catheter-related bloodstream infection (CR-BSI) due to uncommon microorganisms was assessed in a retrospective case-control study over a 9-year period in a tertiary teaching hospital. Uncommon microorganisms were defined as those representing <0·5% of all CR-BSI. Diagnosis of CR-BSI required that the same microorganism was grown from at least one peripheral venous blood culture and a catheter tip culture. Thirty-one episodes of CR-BSI were identified due to 13 different genera and these accounted for 2·3% of all CR-BSI in the hospital. Although these infections were not associated with increased mortality, they occurred in patients with more severe underlying conditions who were receiving prolonged antibiotic therapy.

Is catheter-related candidemia a polyclonal infection?

Diagnosis of catheter-related candidemia (CRC) requires the simultaneous isolation of Candida spp. from both blood and catheter samples. We previously observed that in most CRC cases, the genotype of the yeast found in catheter samples is also recovered from blood. However, it is not clear whether CRC is a polyclonal infection. We prospectively studied 20 patients with CRC caused by Candida albicans, C. parapsilosis, or C. glabrata to analyze whether their infections were polyclonal. As many as 10 colonies per sample (n = 475) isolated from blood (n = 220) and catheter (n = 255) specimens were studied using species-specific microsatellite markers. Genotyping always revealed matches between the Candida spp. from blood and catheter samples. However, 15% of patients had a polyclonal pattern of infection or catheter colonization that was species specific. An additional genotype was found exclusively in the catheters of two patients infected with C. albicans, whereas an additional genotype was noted in the blood culture of a patient infected with C. parapsilosis. Considering only the presence of different genotypes in blood samples, 5% of patients had polyclonal infections. We conclude that most cases of CRC are caused by a single genotype.

Community health coalitions in context: associations between geographic context, member type and length of membership with coalition functions.

The coalition literature recognizes context (geography, demographics and history) as a variable of interest, yet few coalition evaluation studies have focused on it. This study explores the association between geographic context and structures (e.g. member type) with functional characteristics (e.g. decision making or levels of conflict) in a statewide system of community health councils (coalitions). The study was part of a multiyear, statewide evaluation of New Mexico's health councils' contributions to systems-level changes. We adapted the Coalition Self-Assessment Survey (CSAS) for all county health council members and paid council coordinators. Both multilevel univariate and multivariate procedures were used to compare index scores, summaries of CSAS questions used to characterize council functions, with selected demographic variables and region. Member type was associated with decision making and policy capacity; paid staff expressed higher levels of agreement than voting members for both items. Length of membership was associated with decision making, positive leadership and shared vision. Results indicated that geographic context was significantly associated with many functional characteristics. The study highlights the idea that geographic context may influence coalition functioning. Understanding how geographic context influences coalition planning and actions may help explain differences among coalitions that on the surface share common organizational characteristics and external goals.

The quantitative and qualitative recovery of Campylobacter from raw poultry using USDA and Health Canada methods.

Harmonisation of methods between Canadian government agencies is essential to accurately assess and compare the prevalence and concentrations present on retail poultry intended for human consumption. The standard qualitative procedure used by Health Canada differs to that used by the USDA for both quantitative and qualitative methods. A comparison of three methods was performed on raw poultry samples obtained from an abattoir to determine if one method is superior to the others in isolating Campylobacter from chicken carcass rinses. The average percent of positive samples was 34.72% (95% CI, 29.2-40.2), 39.24% (95% CI, 33.6-44.9), 39.93% (95% CI, 34.3-45.6) for the direct plating US method and the US enrichment and Health Canada enrichment methods, respectively. Overall there were significant differences when comparing either of the enrichment methods to the direct plating method using the McNemars chi squared test. On comparison of weekly data (Fishers exact test) direct plating was only inferior to the enrichment methods on a single occasion. Direct plating is important for enumeration and establishing the concentration of Campylobacter present on raw poultry. However, enrichment methods are also vital to identify positive samples where concentrations are below the detection limit for direct plating.

[Translated article] Total hip arthroplasty with shelf acetabuloplasty in dysplastic coxarthrosis, mean follow-up of 7 years.

INTRODUCTION: Developmental dysplasia of the hip is the cause of approximately one third of secondary coxarthrosis. Anatomy alterations make it difficult to place a total hip prosthesis in its anatomical position and for it to be stable in the long term; there are several techniques to achieve this goal. In the present work, we used autograft of the femoral head (shelf graft or reinforced roof), to improve the coverage of the acetabular component with favourable results. MATERIALS AND METHODS: Sixteen cases were included in 14 patients with a diagnosis of developmental dysplasia of the hip (13 women and one man), the mean age was 44.3 years (range 35-68 years), with a mean follow-up of 7 years (range 1-15 years). All the cases were evaluated clinically and radiographically, to demonstrate the osseointegration of the graft and the functional results in the medium term. RESULTS: All the acetabular components were placed in anatomical position (Ranawat technique), the mean percentage of host bone coverage was 54.53% (range 43.28-79.05%), obtaining additional coverage with the bone graft of 45.13%. Osseointegration of the graft of 100% at 12 weeks, resorption of the graft from the sixth month, stabilising in the third postoperative year. Only one case of dislocation is reported, no cases of infection, loosening, heterotopic ossification or revision. CONCLUSION: This procedure has shown good functional results in the medium term with 100% osseointegration, despite cases of severe bone resorption of the graft that does not compromise the stability of the prosthesis.

[Translated article] Total hip arthroplasty with second generation dual mobility system as a treatment for primary coxarthrosis, medium-term results.

INTRODUCTION: Osteoarthritis is a disabling pathology characterised by joint pain and stiffness. A prevalence of coxarthrosis of 7.4% is reported in our country. Total hip joint replacement is indicated in advanced stages, a procedure that is not free of complications, the most frequent being prosthetic dislocation, which can be prevented with dual mobility systems. The following study aims to determine the rate of complications and clinical outcomes in dual mobility systems in primary coxarthrosis. MATERIALS AND METHODS: A retrospective study included 120 cases in 114 patients diagnosed with grade III coxarthrosis, mean age was 62.43 years, with a mean follow-up of 4.5 years. Joint replacement was performed by Hardinge approach. All cases were assessed clinically using the Harris Hip Score (HHS) and radiologically to demonstrate mid-term results. RESULTS: The preoperative value on the HHS scale had a mean of 56.45, postoperative at one month 74.23; 6 months 85.40; 1 year 94.01 and at 5 years 94.84 points, representing a functional improvement of 17.78 postoperative month; 28.95 at 6 months postoperative; 37.56 at one year postoperative and 38.39 points at 5 years postoperative. A complication rate of 3.44%; 0.86% of complications were associated with the prosthetic components. CONCLUSION: The dual mobility system should be considered as a therapeutic option in primary hip joint replacement due to excellent functional results and low complication rates. EVIDENCE LEVEL: IV. Retrospective observational case series study.

Long-term effects of dietary calcium and phosphorus level, and feed form during rearing on egg production, eggshell quality, and bone traits in brown laying hens from 30 to 89 wk of age.

The effects of feeding strategies during rearing (0-16 wk) of brown laying hens on mid and end laying performance (30-89 wk) were studied. The rearing feeding strategies followed a 3 × 2 factorial arrangement with feed form; mash with inclusion of 3% finely ground wheat straw (MWS), crumbles with inclusion of 3% finely ground wheat straw (CWS), and crumbles with inclusion of 3% unground oat hulls as fiber sources (COH) at 2 dietary Ca and P levels (high or low Ca-P). Feed conversion ratio improved with COH and MWS compared with CWS from 30 to 59 wk. Rate of lay and egg mass production showed a feed form × Ca-P interaction from 60 to 89 wk. Low Ca-P led to a higher egg production, but only when COH and MWS were fed. BW at 89 wk was higher with CWS compared to COH and MWS. BW uniformity was better with COH compared to MWS at 51 wk and both CWS and MWS at 67 wk. Tibia characteristics were not clearly affected by treatment, although there was a feed form × Ca-P interaction on compression at 89 wk, where compression was lower with MWS and low vs. high Ca-P. Low Ca-P during rearing led to higher eggshell thickness, compared to high Ca-P at 45 wk of age, but breaking strength was lower with low vs. high Ca-P at 75 wk. Although eggshell quality was affected by Ca-P and there were some interactions with feed form at some ages, the effect was not consistent. There was no clear relationship between eggshell quality and tibia characteristics. It was concluded that feeding low Ca-P in combination with COH and MWS during the rearing period positively affects egg production during late lay. Also, dietary Ca-P levels, compared to commercial practice, can be lowered during rearing, as this will not affect eggshell quality and bone mineralization at later ages.

Total hip arthroplasty with shelf acetabuloplasty in dysplastic coxarthrosis, mean follow-up of 7 years. / Artroplastia total de cadera no cementada con techo armado en coxartrosis displásica, seguimiento medio de 7 años.

Developmental dysplasia of the hip is the cause of approximately one third of secondary coxarthrosis. Anatomy alterations make it difficult to place a total hip prosthesis in its anatomical position and for it to be stable in the long term; there are several techniques to achieve this goal. In the present work, we used autograft of the femoral head (shelf graft or reinforced roof), to improve the coverage of the acetabular component with favorable results. MATERIALS AD METHODS: Sixteen cases were included in 14 patients with a diagnosis of developmental dysplasia of the hip (13 women and one man), the mean age was 44.3 years (range 35-68 years), with a mean follow-up of 7 years (range 1-15 years). All the cases were evaluated clinically and radiographically, to demonstrate the osseointegration of the graft and the functional results in the medium term. RESULTS: All the acetabular components were placed in anatomical position (Ranawat technique), the mean percentage of host bone coverage was 54.53% (range 43.28-79.05%), obtaining additional coverage with the bone graft of 45.13%. Osseointegration of the graft of 100% at 12 weeks, resorption of the graft from the sixth month, stabilizing in the third postoperative year. Only one case of dislocation is reported, no cases of infection, loosening, heterotopic ossification or revision. CONCLUSION: This procedure has shown good functional results in the medium term with 100% osseointegration, despite cases of severe bone resorption of the graft that does not compromise the stability of the prosthesis.

Differential time to positivity (DTTP) for the diagnosis of catheter-related bloodstream infection: do we need to obtain one or more peripheral vein blood cultures?

The ideal number of blood samples to be obtained from peripheral veins (PVs) when differential time to positivity (DTTP) is being performed is an unresolved issue and most institutions obtain a single set. Our objective was to assess the number of proven central line-associated bloodstream infection (CLABSI) episodes that would have been recovered if blood had been cultured from one or two PVs. We performed a retrospective study in patients with proven CLABSI in which catheter lumens and two or more PV blood cultures were taken simultaneously. We calculated the number of episodes that would have been recovered if the culture of one or more PV blood cultures had been artificially eliminated. During a period of 4 years, we collected 60 episodes of proven CLABSI. Overall, if one PV culture had been eliminated in patients with two or three PV blood cultures, we would have documented 91.8% (p=0.362) and 96.9% (p>0.999) of episodes, respectively. If we had eliminated two PV blood cultures in patients with three PV blood cultures, 90.8% (p>0.999) of episodes would have been documented. When performing the DTTP technique to confirm CLABSI, a single paired PV blood culture was not associated with a significant number of missed CLABSI episodes.

Increase in the frequency of catheter-related bloodstream infections during the COVID-19 pandemic: a plea for control.

BACKGROUND: The incidence of nosocomial infections including ventilator-associated pneumonia and bacteraemia has been described during the COVID-19 pandemic. However, information regarding the impact of COVID-19 on the incidence of catheter-related bloodstream infections (CR-BSIs) is very limited. AIM: To evaluate the impact of the COVID-19 pandemic in the evolution of CR-BSIs in a large hospital. METHODS: This was a retrospective study comparing the incidence, aetiology and outcome of CR-BSIs during the months of March to May 2019 (pre-pandemic) and 2020 (during the pandemic). FINDINGS: The number of patients with one or more CR-BSIs in 2019 and 2020 were 23 and 58, respectively (1.89 vs 5.53/1000 admissions); P<0.001. Median time from catheter implantation to demonstration of CR-BSI was 27.5 days (range 11.75-126.00 days) in the 2019 cases and 16.0 days (range 11.00-23.50 days) in the 2020 population (P=0.032). CONCLUSIONS: A dramatic increase of CR-BSIs was found during the COVID-19 pandemic. Reinforcement of classic and new preventive measures is necessary.

Unresolved issues in the epidemiology and diagnosis of bacteremia: an opinion paper.

Bacteremia is an important cause of morbidity and mortality worldwide and, despite the diagnostic and therapeutic advances of the last decades, the evidence supporting many diagnostic aspects of bacteremia is scarce. Information on the epidemiological evolution of this entity is limited and many methodological aspects of blood culture collection and analysis are under discussion. Furthermore, the recommendations of the main scientific societies on many of these aspects are variable and, in many cases, have not been updated recently. In this scenario, we have arranged a series of questions on different aspects of bacteremia and reviewed the literature trying to find proper answers for them. We offer our opinion on the topics where the evidence was weak. The topics covered include epidemiological aspects of bacteremia, indications for blood culture extraction, methods for obtaining and incubating samples, or ways of transmitting results from the microbiology laboratory. We do not intend to summarize the current clinical practice guidelines, nor will we deal with the therapeutic management of this entity. The aim of this paper is to review the current perspective on the diagnosis of bacteremia with a critical approach, to point out the gaps in the literature, to offer the opinion of a team dedicated to infectious diseases and clinical microbiology, and to identify some areas of knowledge on which future studies should focus.

[Evaluation of bleeding, pain and operative time of the midvasto versus medial parapatellar approach in primary total knee arthroplasty for grade IV osteoarthrosis]. / Evaluación del sangrado, dolor y tiempo quirúrgico del abordaje midvasto versus parapatelar medial en artroplastía total de rodilla primaria por osteoartrosis grado IV.

INTRODUCTION: total knee arthroplasty is a common procedure in orthopedic surgery for treating grade IV knee osteoarthritis. This procedure reduces pain and improves functionality. However, the results according to the approach are different, it is not clear which surgical approach is clearly superior. The objective of this study is to evaluate the time and post-surgical bleeding, as well as the postoperative pain of the midvasto versus medial parapatellar approach in primary total knee arthroplasty in grade IV gonarthrosis. MATERIAL AND METHODS: an observational, comparative, retrospective study was carried out from June 1, 2020 to December 31, 2020, including beneficiaries of the Mexican Social Security Institute over 18 years of age with a diagnosis of grade IV knee osteoarthritis scheduled for primary total knee arthroplasty in the absence of other inflammatory pathology, previous osteotomies or coagulopathies. RESULTS: of 99 patients who underwent the midvasto approach (group M) and 100 patients to the medial parapatellar approach (group T), there was preoperative hemoglobin 14.7 g/l group M and 15.2 g/l group T, reduction was 5.0 g/l group M and 4.6 g/l group T. Significant pain reduction in both groups without significant difference; from 6.7 to 3.2 group M and from 6.7 to 3.1 group T. The surgical time was significantly longer with the medial parapatellar approach (98.7 versus 89.2 minutes). CONCLUSIONS: both approaches represent an excellent access route to perform primary total knee arthroplasty; however, no significant differences were found in the volume of bleeding or in the reduction of pain, the midvaste approach was associated with shorter surgical time and less involvement of flexion of the knee. Therefore, the midvasto approach is recommended in patients undergoing primary total knee arthroplasty.

INTRODUCCIÓN: la artroplastía total de rodilla es un procedimiento común en la cirugía ortopédica de tratamiento para gonartrosis grado IV. Este procedimiento disminuye el dolor y mejora la funcionalidad. Sin embargo, los resultados según el abordaje son distintos, no existe evidencia sobre qué abordaje quirúrgico sea claramente superior. El objetivo de este estudio es evaluar el tiempo y sangrado transquirúrgico, así como el dolor postquirúrgico del abordaje midvasto versus parapatelar medial en artroplastía total de rodilla primaria en gonartrosis grado IV. MATERIAL Y MÉTODOS: se realizó estudio observacional, comparativo, retrospectivo del 01 de Junio de 2020 al 31 de Diciembre de 2020 incluyendo derechohabientes del Instituto Mexicano del Seguro Social, mayores de 18 años con diagnóstico de gonartrosis grado IV, programados para artroplastía total de rodilla primaria en ausencia de otra patología inflamatoria, osteotomías previas o coagulopatías. RESULTADOS: noventa y nueve pacientes que fueron sometidos a abordaje midvasto (grupo M) y 100 pacientes a abordaje parapatelar medial (grupo T) con hemoglobina preoperatoria 14.7 g/l grupo M y 15.2 g/l grupo T, la reducción fue de 5.0 g/l grupo M y 4.6 g/l grupo T. Dolor en ambos grupos sin diferencia significativa; de 6.7 a 3.2 grupo M y de 6.7 a 3.1 grupo T. Tiempo quirúrgico mayor con el abordaje parapatelar medial (98.7 versus 89.2 minutos). CONCLUSIONES: ambos abordajes representan excelente vía de acceso para realizar artroplastía total primaria de rodilla; sin embargo, no se encontraron diferencias significativas en el volumen de sangrado ni en la reducción del dolor, el abordaje midvasto se asoció con menor tiempo quirúrgico y menor afectación de la flexión de la rodilla, por lo que se recomienda el abordaje midvasto en pacientes sometidos a artroplastía total de rodilla primaria.

Mutations in classical swine fever virus NS4B affect virulence in swine.

NS4B is one of the nonstructural proteins of classical swine fever virus (CSFV), the etiological agent of a severe, highly lethal disease of swine. Protein domain analysis of the predicted amino acid sequence of the NS4B protein of highly pathogenic CSFV strain Brescia (BICv) identified a putative Toll/interleukin-1 receptor (TIR)-like domain. This TIR-like motif harbors two conserved domains, box 1 and box 2, also observed in other members of the TIR superfamily, including Toll-like receptors (TLRs). Mutations within the BICv NS4B box 2 domain (V2566A, G2567A, I2568A) produced recombinant virus NS4B.VGIv, with an altered phenotype displaying enhanced transcriptional activation of TLR-7-induced genes in swine macrophages, including a significant sustained accumulation of interleukin-6 (IL-6) mRNA. Transfection of swine macrophages with the wild-type NS4B gene partially blocked the TLR-7-activating effect of imiquimod (R837), while transfection with the NS4B gene harboring mutations in either of the putative boxes displayed decreased blocking activity. NS4B.VGIv showed an attenuated phenotype in swine, displaying reduced replication in the oronasal cavity and limited spread from the inoculation site to secondary target organs. Furthermore, the level and duration of IL-6 production in the tonsils of pigs intranasally inoculated with NS4B.VGIv were significantly higher than those for animals infected with BICv. The peak of IL-6 production in infected animals paralleled the ability of animals infected with NS4B.VGIv to resist challenge with virulent BICv. Interestingly, treatment of peripheral blood mononuclear cell cultures with recombinant porcine IL-6 results in a significant decrease in BICv replication.