Combination of Tele-Cardiology Tools for Cardiovascular Risk Stratification in Primary Care: Data from the PROVAR+ Study. / Combinação de Ferramentas de Telecardiologia para Estratificação de Risco Cardiovascular na Atenção Primária: Dados do Estudo PROVAR.

BACKGROUND: Tele-cardiology tools are valuable strategies to improve risk stratification. OBJECTIVE: We aimed to evaluate the accuracy of tele-electrocardiography (ECG) to predict abnormalities in screening echocardiography (echo) in primary care (PC). METHODS: In 17 months, 6 health providers at 16 PC units were trained on simplified handheld echo protocols. Tele-ECGs were recorded for final diagnosis by a cardiologist. Consented patients with major ECG abnormalities by the Minnesota code, and a 1:5 sample of normal individuals underwent clinical questionnaire and screening echo interpreted remotely. Major heart disease was defined as moderate/severe valve disease, ventricular dysfunction/hypertrophy, pericardial effusion, or wall-motion abnormalities. Association between major ECG and echo abnormalities was assessed by logistic regression as follows: 1) unadjusted model; 2) model 1 adjusted for age/sex; 3) model 2 plus risk factors (hypertension/diabetes); 4) model 3 plus history of cardiovascular disease (Chagas/rheumatic heart disease/ischemic heart disease/stroke/heart failure). P-values < 0.05 were considered significant. RESULTS: A total 1,411 patients underwent echo; 1,149 (81%) had major ECG abnormalities. Median age was 67 (IQR 60 to 74) years, and 51.4% were male. Major ECG abnormalities were associated with a 2.4-fold chance of major heart disease on echo in bivariate analysis (OR = 2.42 [95% CI 1.76 to 3.39]), and remained significant after adjustments in models (p < 0.001) 2 (OR = 2.57 [95% CI 1.84 to 3.65]), model 3 (OR = 2.52 [95% CI 1.80 to3.58]), and model 4 (OR = 2.23 [95%CI 1.59 to 3.19]). Age, male sex, heart failure, and ischemic heart disease were also independent predictors of major heart disease on echo. CONCLUSIONS: Tele-ECG abnormalities increased the likelihood of major heart disease on screening echo, even after adjustments for demographic and clinical variables.

FUNDAMENTO: As ferramentas de telecardiologia são estratégias valiosas para melhorar a estratificação de risco. OBJETIVO: Objetivamos avaliar a acurácia da tele-eletrocardiografia (ECG) para predizer anormalidades no ecocardiograma de rastreamento na atenção primária. MÉTODOS: Em 17 meses, 6 profissionais de saúde em 16 unidades de atenção primária foram treinados em protocolos simplificados de ecocardiografia portátil. Tele-ECGs foram registrados para diagnóstico final por um cardiologista. Pacientes consentidos com anormalidades maiores no ECG pelo código de Minnesota e uma amostra 1:5 de indivíduos normais foram submetidos a um questionário clínico e ecocardiograma de rastreamento interpretado remotamente. A doença cardíaca grave foi definida como doença valvular moderada/grave, disfunção/hipertrofia ventricular, derrame pericárdico ou anormalidade da motilidade. A associação entre alterações maiores do ECG e anormalidades ecocardiográficas foi avaliada por regressão logística da seguinte forma: 1) modelo não ajustado; 2) modelo 1 ajustado por idade/sexo; 3) modelo 2 mais fatores de risco (hipertensão/diabetes); 4) modelo 3 mais história de doença cardiovascular (Chagas/cardiopatia reumática/cardiopatia isquêmica/AVC/insuficiência cardíaca). Foram considerados significativos valores de p < 0,05. RESULTADOS: No total, 1.411 pacientes realizaram ecocardiograma, sendo 1.149 (81%) com anormalidades maiores no ECG. A idade mediana foi de 67 anos (intervalo interquartil de 60 a 74) e 51,4% eram do sexo masculino. As anormalidades maiores no ECG se associaram a uma chance 2,4 vezes maior de doença cardíaca grave no ecocardiograma de rastreamento na análise bivariada (OR = 2,42 [IC 95% 1,76 a 3,39]) e permaneceram significativas (p < 0,001) após ajustes no modelo 2 (OR = 2,57 [IC 95% 1,84 a 3,65]), modelo 3 (OR = 2,52 [IC 95% 1,80 a 3,58]) e modelo 4 (OR = 2,23 [IC 95% 1,59 a 3,19]). Idade, sexo masculino, insuficiência cardíaca e doença cardíaca isquêmica também foram preditores independentes de doença cardíaca grave no ecocardiograma. CONCLUSÕES: As anormalidades do tele-ECG aumentaram a probabilidade de doença cardíaca grave no ecocardiograma de rastreamento, mesmo após ajustes para variáveis demográficas e clínicas.

Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD): A matched analysis from the Paediatric PSC Consortium.

BACKGROUND: Data on oral vancomycin for primary sclerosing cholangitis (PSC)-associated inflammatory bowel disease (IBD) are limited. AIMS: Using data from the Paediatric PSC Consortium, to examine the effect of vancomycin on IBD activity. METHODS: In this retrospective multi-centre cohort study, we matched vancomycin-treated and untreated patients (1:3) based on IBD duration at the time of primary outcome assessment. The primary outcome was Physician Global Assessment (PGA) of IBD clinical activity after 1 year (±6 months) of vancomycin. We used generalised estimating equations (GEE) to examine the association between vancomycin and PGA remission, adjusting for IBD type, severity and medication exposures. Secondary outcomes included serum labs and endoscopic remission (global rating of no activity) among those with available data and also analysed with GEE. RESULTS: 113 PSC-IBD patients received vancomycin (median age 12.7 years, 63% male). The matched cohort included 70 vancomycin-treated and 210 untreated patients. Vancomycin was associated with greater odds of IBD clinical remission (odds ratio [OR] 3.52, 95% CI 1.97-6.31; adjusted OR [aOR] 5.24, 95% CI 2.68-10.22). Benefit was maintained in sensitivity analyses restricted to non-transplanted patients and those with baseline moderate-severe PGA. Vancomycin was associated with increased odds of endoscopic remission (aOR 2.76, 95% CI 1.002-7.62; N = 101 with data), and with lower CRP (p = 0.03) and higher haemoglobin and albumin (both p < 0.01). CONCLUSION: Vancomycin was associated with greater odds of IBD clinical and endoscopic remission. Additional, preferably randomised, controlled studies are needed to characterise efficacy using objective markers of mucosal inflammation, and to examine safety and define optimal dosing.

Autosomal Recessive IL-12p40 Deficiency due to a Mutation in the IL12B Gene: Report of a Brazilian Patient with Lymph Node Mycobacterial Infection.

Background: Autosomal recessive interleukin (IL)-12p40 deficiency is a genetic etiology of Mendelian susceptibility to mycobacterial disease (MSMD). It has been described in ∼50 patients, usually with onset at childhood with Bacille Calmette-Guérin (BCG) and Salmonella infections. Case Presentation: A male patient born to consanguineous parents was diagnosed with presumed lymph node MSMD at the age of 13 years after ocular symptoms. A positive history of inborn error of immunity was present: BCG reaction, skin abscess, and recurrent oral candidiasis. Abnormal measurements of cytokine levels, IL-12p40 and interferon-gamma (IFN-γ), lead to the diagnosis of MSMD. Genetic analysis showed a mutation in exon 7 of the IL12B gene. Currently, the patient is alive under prophylactic antibiotics. Conclusion: We report a rare case of IL-12p40 deficiency in a Latin American patient. Medical history was crucial for immune defect suspicion, as confirmed by precision diagnostic medicine tools.

The Influence of Tibial Tubercle-Sparing Slope-Reducing Osteotomy on Patellar Height in Patients Undergoing Revision ACL Reconstruction.

BACKGROUND: A posterior tibial slope (PTS) >12° is an independent risk factor for anterior cruciate ligament (ACL) graft rupture, and a high tibial osteotomy (HTO) for slope correction can help avoid it. Management of patellar height is of major concern when performing HTO. PURPOSE: To evaluate the effect of tibial tubercle-sparing anterior closing-wedge osteotomy on patellar height in revision ACL reconstruction (ACLR). STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients who underwent arthroscopic revision ACLR combined with retro-tibial tubercle anterior closing-wedge HTO (ACW-HTO) between January 1, 2016, and March 31, 2021, were assessed for eligibility. Patellar height was measured on full weightbearing lateral radiographs according to the Insall-Salvati index (ISI) and Caton-Deschamps index (CDI) or frontal radiographs using the femoral patellar height index. The PTS was evaluated using the proximal anatomic axis of the tibia on standard short lateral radiographs. The delta (postoperative - preoperative) and the ratio (preoperative/postoperative) of the 3 patellar height indices and PTS were calculated. Preoperative and postoperative patellar heights were compared using independent t tests for each index. Also investigated was whether patients changed patellar height category (baja, normal, or alta) after slope osteotomy. RESULTS: Among 475 revision ACLRs, 47 tibial tubercle-sparing ACW-HTOs were retained for analysis. No significant difference in patellar height was found between pre- and postoperative radiographs regardless of the index (preoperative - postoperative) (ISI: 1.0 ± 0.2 - 0.9 ± 0.2, P = .1729; CDI: 1.0 ± 0.2 - 1.0 ± 0.2, P = .4034; femoral patellar height index: 1.5 ± 0.2 - 1.5 ± 0.2; P = .5130). Fifteen patients (31.9%) exhibited a postoperative change in their patellar height category when measured by the ISI (6 moved up a category, 9 moved down one), and 18 patients (38.3%) changed category according to the CDI (10 moved up a category, 8 moved down one). No significant difference was found between pre- and postoperative patellar height among these patients (ISI: P = .2418; CDI: P = .3005). CONCLUSION: Changes in patellar height ratio are common after tibial tubercle-sparing ACW-HTO in patients undergoing revision ACLR. The clinical effect of these changes is unknown, and further study is needed to investigate whether they may result in patellofemoral symptoms.

Agreement between Handheld and Standard Echocardiography for Diagnosis of Latent Rheumatic Heart Disease in Brazilian Schoolchildren from High-Prevalence Settings (Agreement between Screening and Standard Echo for RHD).

Introduction: Handheld echocardiography (echo) is the tool of choice for rheumatic heart disease (RHD) screening. We aimed to assess the agreement between screening and standard echo for latent RHD diagnosis in schoolchildren from an endemic setting. Methods: Over 14 months, 3 nonphysicians used handheld machines and the 2012 WHF Criteria to determine RHD prevalence in consented schoolchildren from Brazilian low-income public schools. Studies were interpreted by telemedicine by 3 experts (Brazil, US). RHD-positive children (borderline/definite) and those with congenital heart disease (CHD) were referred for standard echo, acquired and interpreted by a cardiologist. Agreement between screening and standard echo, by WHF subgroups, was assessed. Results: 1390 students were screened in 6 schools, with 110 (7.9%, 95% CI 6.5-9.5) being screen positive (14 ± 2 years, 72% women). Among 16 cases initially diagnosed as definite RHD, 11 (69%) were confirmed, 4 (25%) reclassified to borderline, and 1 to normal. Among 79 cases flagged as borderline RHD, 19 (24%) were confirmed, 50 (63%) reclassified to normal, 8 (10%) reclassified as definite RHD, and 2 had mild CHD. Considering the 4 diagnostic categories, kappa was 0.18. In patients with borderline RHD reclassified to non-RHD, the most frequent WHF criterion was B (isolated mitral regurgitation, 64%), followed by A (2 mitral valve morphological features, 31%). In 1 patient with definite RHD reclassified to normal, the WHF criterion was D (borderline RHD in aortic and mitral valves). After standard echo, RHD prevalence was 3.2% (95% CI 2.3-4.2). Conclusions: Although practical, RHD screening with handheld devices tends to overestimate prevalence.

Separation of the heme protein cytochrome C using a 3D structured graphene oxide bionanocomposite as an adsorbent.

Proteins are of great importance for medicine and the pharmaceutical and food industries. However, proteins need to be purified prior to their application. This work investigated the application of a hydrogel bionanocomposite based on agar and graphene oxide (GO) for capturing cytochrome C (Cyto C) heme protein by adsorption from aqueous solutions with other proteins. Although applications of GO-based materials in adsorption are widely studied, the focus on semi-continuous processes remains limited. Adsorption experiments were carried out in batch and fixed bed columns. The effect of pH and ionic strength on adsorption was investigated, and there is evidence that electrostatic interactions between Cyto C and the nanocomposite were favoured at pH = 7; the adsorption capacity decreased as NaCl and KCl concentrations increased, ascribed to the weak electrostatic interaction between the protein and GO active sites in the bionanocomposite. All adsorption isotherm models (Langmuir, Freundlich, Sips) used gave suitable adjustments to the equilibrium experimental data and the kinetic models applied. The maximum adsorption capacity predicted by the Langmuir isotherm was ∼400 mgCytoC gadsorbent,dry-1, and the adsorption thermodynamics indicated a physisorption process. Tests were performed to evaluate the co-adsorption in batch, and the composite was effective in adsorbing Cyto C in solution with bovine serum albumin (BSA) and L-phenylalanine. Fixed bed tests were performed, and although protein adsorption onto nanoparticles can be challenging, the Cyto C adsorbed could be successfully recovered after desorption. Overall, the GO-based hydrogel was an effective method for cytochrome C adsorption, exhibiting a notorious potential for applications in protein separation processes.

Clinical outcome of iterative meniscal suture after ACL reconstruction at a minimum of 2 years' follow-up.

INTRODUCTION: Failure rates in meniscal suture associated to ACL reconstruction range from 10 to 26.9%, often leading to meniscectomy. In young patients, the wish to conserve the meniscus may lead to iterative suture, if the lesion allows. There are no data available for clinical results of repeat meniscal suture at the same site as the primary lesion in a stabilized knee. The immediate socioeconomic cost, compared to meniscectomy, needs to be taken into account, and benefit needs to be demonstrated. The main aim of the present study was to assess the rate of secondary meniscectomy after iterative meniscal suture in stabilized knees. The study hypothesis was that failure rates are higher in iterative isolated meniscal suture after ligament reconstruction than in primary repair. MATERIAL AND METHODS: This single-center retrospective study analyzed patients receiving iterative meniscal suture on stable knee, between 2009 and 2019, with a minimum 26 months' follow-up. Twenty-three patients were analyzed: 15 male, 8 female; mean age at iterative suture, 28.1±7.9 years (range, 14-49 years); mean BMI, 24.2±2.9kg/m2 (range, 19-31). Mean time to recurrence was 38.9±25.1 months (range, 6-93 months). Initial ACL graft used the patellar ligament in 69.6% of cases (n=16) and the hamstrings in 30.4% (n=7). Mean differential laximetry before iterative suture was 1.7±0.3mm (range, 1.2-2.3mm). Iterative suture was in the medial meniscus in 69.6% of cases (16/23) and in the lateral meniscus in 30.4% (7/23). Risk factors for failure, defined by requirement for meniscectomy, were assessed. Functional results were assessed on Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) score and Tegner score. RESULTS: The failure rate was 48% (11/23), incorporating all lesions together. Bucket-handle tear was most frequently associated with failure (91%; p<0.01). There was significant improvement after iterative suture in subjective IKDC score (51.6±15.2 vs. 81.3±15.6; p<0.001) and KOOS scores: symptoms and stiffness, 66.6±13.7 vs. 91.1±7.53 (p<0.001); pain, 79.2±12.7 vs. 93.4±7.4 (p<0.01); function, 91.3±11.2 vs. 97.9±4.44 (p<0.001); quality of life, 38.1±23.2 vs. 62.3±30.1 (p<0.001). CONCLUSION: The failure rate for iterative meniscal suture on stabilized knee was 48%. Bucket-handle tear was a major risk factor for failure (91%). Despite these high failure rates, functional results systematically improved. LEVEL OF EVIDENCE: IV.

Distal femoral osteotomy planning: Reversed Miniaci's method is more accurate than Dugdale and Paley methods.

PURPOSES: The purpose of this study was to validate the reversed Miniaci method for distal femoral osteotomies and to compare the accuracy with Dugdale and Paley methods. METHODS: Between January 2019 and October 2021, 59 DFO were performed in a single center. Following application of the eligibility and exclusion criteria, radiographic measurements and analysis was performed for 24 patients by two independent observers, then repeated after one month. Medical planning software: PeekMed v2.3.7.6® was used. For all patients the following measurements were performed: Hip-Knee-Ankle (HKA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), joint line obliquity (JLO), width of the proximal tibia and the weight-bearing line (WBL). Each image was then analysed using the following planning methods for realignment surgery: Reversed Miniaci, Dugdale and Paley. Measurements were recorded post deformity correction. Difference between target and post-correction WBL was evaluated. This difference was adjusted by the objective in order to limit biases related to the different objectives according to the method. RESULTS: Eighteen patients were managed for a varus osteotomy and 6 for a valgus osteotomy. Preoperative data was, HKA at 176.7±6.3, mLDFA at 90.6±5.4, MPTA 88.9±1.1, a WBL for valgus 80.9%±9.1 and for varus deformity 23.5%±11.7. Inter- and intra-rater reliability was>0.8 for every method. After normalizing reported precision on the amount of correction expected, reversed Miniaci method was the most accurate with a mean deviation from the target of 3%, compared to the Dugdale's method with 9% (p<0.001) and to Paley's method with 8.6% (p<0.001). CONCLUSION: The reversed Miniaci method is effective and reliable for planning distal femoral osteotomies. Compared to other planning methods, it is the most accurate approach for achieving a correction goal. LEVEL OF EVIDENCE: IV; retrospective cohort study.

Heterogeneities of the impact of public health policies on HIV/AIDS indicators in Brazil according to sociodemographic factors: A real-life study.

INTRODUCTION: The impact of specific policies on HIV care has been scarcely investigated. In this study we aimed to analyze the impact of the Treatment For All policy (TFA-2013) and the adoption of integrase strand transfer inhibitors (INSTIs-2017) as first-line therapy on clinical indicators of people living with HIV (PLHIV) in Brazil. METHODS: We assessed the public database of Brazil's Ministry of Health and extracted data from 2009 to 2019. We investigated the impact of TFA and INSTIs with a time-series analysis of four health indicators in PLHIV: antiretroviral treatment (ART) initiation with a CD4+ count >500/mm3 ; ART initiation <1 month after the first CD4+ measurement; viral load suppression (VLS); and treatment adherence. We explored trends over time by gender, age, macroregion of residency and municipal-level social vulnerability index. RESULTS: We included 753 316 PLHIV in 2019. Most were males (64.81%) in the 30-49 years age category (50.86%). We observed an overall improvement in all HIV clinical indicators, with notable impact of TFA on timely ART initiation and VLS, and mild impact of INSTIs on treatment adherence. Such improvements were heterogeneous, with remarkable gaps in gender, age and socioeconomic groups that have persisted over time. Indicators point to inferior outcomes among children, older adults, women and people living in socially vulnerable locations. CONCLUSIONS: Recent Brazilian public policies have had positive impacts on key HIV clinical indicators. However, our results highlight the need for specific policies to improve HIV care for children, older adults, women and socially vulnerable groups.

Agar/graphene oxide hydrogels as nano-bioadsorbents: a comparative analysis for dye removal.

Nano-biocomposite hydrogel samples were produced using graphene oxide (GO) and agar and applied as adsorbents of organic components in water. The hydrogels were prepared by varying the wt% of Agar and GO. The samples were characterized, and batch adsorption experiments evaluated the effect of initial pH, equilibrium isotherms, and kinetics for the adsorption of the anionic dye Acid Orange 7 (AO) and the cationic dyes Nile Blue A (NB) and methylene blue (MB) in an aqueous medium. Overall, both hydrogel samples exhibited satisfactory results for removing NB and MB; however, there was no effective removal for the anionic dye AO. Adsorption equilibrium isotherms were obtained, and Freundlich, Langmuir, and Sips models were fitted to the experimental equilibrium data; moreover, kinetic data were adjusted to driving force models and particle mass balance. The maximum experimental adsorption capacities, 141.48 mg·g-1 (MB) and 284.69 mg·g-1 (NB), were obtained, on a dry basis, for the sample produced with 70 wt% of agar and 30 wt% of GO. Both hydrogels exhibited remarkable regenerative potential for NB and MB, with the adsorption capacity remaining constant, even after five adsorption/desorption cycles.

CLINICAL, LABORATORIAL AND EVOLUTIONARY ASPECTS OF PEDIATRIC PATIENTS WITH LIVER DISEASE DUE TO ALPHA 1-ANTITRYPSIN DEFICIENCY.

BACKGROUND: Alpha 1-antitrypsin deficiency (AATD) is a hereditary codominant autosomal disease. This liver disease ranges from asymptomatic cases to terminal illness, which makes early recognition and diagnosis challenging. It is the main cause of pediatric liver transplantation after biliary atresia. OBJECTIVE: To describe the clinical characteristics, as well as those of histologic and laboratory tests, phenotypic and/or genetic evaluation and evolution of a cohort of pediatric patients with AATD. METHODS: This is a retrospective observational study of 39 patients with confirmed or probable AATD (without phenotyping or genotyping, but with suggestive clinical features, low serum alpha 1-antitrypsin (AAT) level and liver biopsy with PAS granules, resistant diastasis). Clinical, laboratory and histological varia-bles, presence of portal hypertension (PH) and survival with native liver have been analyzed. RESULTS: A total of 66.7% of 39 patients were male (26/39). The initial manifestation was cholestatic jaundice in 79.5% (31/39). Liver transplantation was performed in 28.2% (11/39) of patients. Diagnosis occurred at an average of 3.1 years old and liver transplantation at 4.1 years of age. 89.2% (25/28) of the patients with confirmed AATD were PI*ZZ or ZZ. The average AAT value on admission for PI*ZZ or ZZ patients was 41.6 mg/dL. All transplanted patients with phenotyping or genotyping were PI*ZZ (or ZZ). Those who were jaundiced on admission were earlier referred to the specialized service and had higher levels of GGT and platelets on admission. There was no significant difference in the survival curve when comparing cholestatic jaundiced to non-cholestatic jaundiced patients on admission. Comparing patients who did or did not progress to PH, higher levels of AST and APRI score at diagnosis (P=0.011 and P=0.026, respectively) were observed and in the survival curves patients with PH showed impairment, with 20.2% survival with native liver in 15 years. CONCLUSION: Jaundice is an important clinical sign that motivates referral to a specialist, but it does not seem to compromise survival with native liver. Patients progressing to PH had higher AST, APRi score on admission and significantly impaired survival with native liver. It is important to pay attention to these signs in the follow-up of patients with AATD.

Aspectos clínicos, laboratoriais e evolutivos de pacientes pediátricos com doença hepática por deficiência de alfa 1-antitripsina / Clinical, laboratorial and evolutionary aspects of pediatric patients with liver disease due to alpha 1-antitrypsin deficiency

ABSTRACT Background: Alpha 1-antitrypsin deficiency (AATD) is a hereditary codominant autosomal disease. This liver disease ranges from asymptomatic cases to terminal illness, which makes early recognition and diagnosis challenging. It is the main cause of pediatric liver transplantation after biliary atresia. Objective: To describe the clinical characteristics, as well as those of histologic and laboratory tests, phenotypic and/or genetic evaluation and evolution of a cohort of pediatric patients with AATD. Methods: This is a retrospective observational study of 39 patients with confirmed or probable AATD (without phenotyping or genotyping, but with suggestive clinical features, low serum alpha 1-antitrypsin (AAT) level and liver biopsy with PAS granules, resistant diastasis). Clinical, laboratory and histological varia­bles, presence of portal hypertension (PH) and survival with native liver have been analyzed. Results: A total of 66.7% of 39 patients were male (26/39). The initial manifestation was cholestatic jaundice in 79.5% (31/39). Liver transplantation was performed in 28.2% (11/39) of patients. Diagnosis occurred at an average of 3.1 years old and liver transplantation at 4.1 years of age. 89.2% (25/28) of the patients with confirmed AATD were PI*ZZ or ZZ. The average AAT value on admission for PI*ZZ or ZZ patients was 41.6 mg/dL. All transplanted patients with phenotyping or genotyping were PI*ZZ (or ZZ). Those who were jaundiced on admission were earlier referred to the specialized service and had higher levels of GGT and platelets on admission. There was no significant difference in the survival curve when comparing cholestatic jaundiced to non-cholestatic jaundiced patients on admission. Comparing patients who did or did not progress to PH, higher levels of AST and APRI score at diagnosis (P=0.011 and P=0.026, respectively) were observed and in the survival curves patients with PH showed impairment, with 20.2% survival with native liver in 15 years. Conclusion: Jaundice is an important clinical sign that motivates referral to a specialist, but it does not seem to compromise survival with native liver. Patients progressing to PH had higher AST, APRi score on admission and significantly impaired survival with native liver. It is important to pay attention to these signs in the follow-up of patients with AATD.

RESUMO Contexto: Deficiência de alfa 1-antitripsina (DAAT) é uma doença hereditária, de caráter autossômico codominante. A apresentação da doença hepática varia desde casos assintomáticos até doença terminal, o que dificulta reconhecimento e diagnóstico precoces. É a principal causa de transplante hepático pediátrico após atresia de vias biliares. Objetivo: Descrever as características clínicas, de exames laboratoriais, histológicos, avaliação fenotípica e/ou genética e sobrevida de uma coorte de pacientes pediátricos com DAAT. Métodos: Estudo observacional retrospectivo de 39 pacientes com diagnóstico de DAAT confirmada ou provável (sem fenotipagem ou genotipagem, mas com clínica sugestiva, baixo nível sérico de alfa 1-antitripsina (A1AT) e biópsia hepática com grânulos PAS, diástase resistentes). Variáveis clínicas, laboratoriais, histológicas, presença de hipertensão portal (HP) e sobrevida com fígado nativo foram analisadas. Resultados: Dos 39 pacientes, 66,7% eram do sexo masculino (26/39). A manifestação inicial foi icterícia colestática em 79,5% (31/39). Em 28,2% (11/39) houve necessidade de transplante hepático. O diagnóstico ocorreu com uma idade média de 3,1 anos e, o transplante hepático, 4,1 anos. Dos pacientes com DAAT confirmada, 89,2% (25/28) eram PI*ZZ ou ZZ. O valor médio de A1AT na admissão de pacientes PI*ZZ ou ZZ foi 41,6 mg/dL. Todos os transplantados com fenotipagem ou genotipagem eram PI*ZZ (ou ZZ). Os ictéricos à admissão foram referenciados mais cedo ao serviço especializado e apresentaram níveis mais elevados de GGT e plaquetas à admissão. Não houve diferença significativa na curva de sobrevida ao compararmos icterícia colestática ou não à admissão. Ao comparar os pacientes que progrediram ou não para HP, observou-se níveis mais elevados de AST e APRI escore ao diagnóstico (P=0,011 e P=0,026, respectivamente) e, nas curvas de sobrevida, pacientes com HP apresentaram comprometimento, com 20,2% de sobrevida com fígado nativo em 15 anos. Conclusão: Icterícia é um sinal clínico importante que motiva o encaminhamento ao especialista, mas parece não comprometer a sobrevida com fígado nativo. Pacientes com evolução para HP tiveram AST e escore APRi mais elevados à admissão e comprometimento significativo da sobrevida com fígado nativo. Importante atentar a esses sinais no seguimento de pacientes com DAAT.

Evaluation of the impact of large language learning models on articles submitted to Orthopaedics & Traumatology: Surgery & Research (OTSR): A significant increase in the use of artificial intelligence in 2023.

INTRODUCTION: There has been an unprecedented rise is the use of artificial intelligence (AI) amongst medical fields. Recently, a dialogue agent called ChatGPT (Generative Pre-trained Transformer) has grown in popularity through its use of large language models (LLM) to clearly and precisely generate text on demand. However, the impact of AI on the creation of scientific articles is remains unknown. A retrospective study was carried out with the aim of answering the following questions: identify the presence of text generated by LLM before and after the increased usage of ChatGPT in articles submitted in OTSR; determine if the type of article, the year of submission, and the country of origin, influenced the proportion of text generated, at least in part by AI. MATERIAL AND METHODS: A total of 390 English articles were submitted to OTSR in January, February and March 2022 (n=204) and over the same months of 2023 (n=186) were analyzed. All articles were analyzed using the ZeroGPT tool, which provides an assumed rate of AI use expressed as a percentage. A comparison of the average rate of AI use was carried out between the articles submitted in 2022 and 2023. This comparison was repeated keeping only the articles with the highest percentage of suspected AI use (greater than 10 and 20%). A secondary analysis was carried out to identify risk factors for AI use. RESULTS: The average percentage of suspected LLM use in the entire cohort was 11%±6, with 160 articles (41.0%) having a suspected AI rate greater than 10% and 61 (15.6%) with an assumed AI rate greater than 20%. A comparison between articles submitted in 2022 and 2023 revealed a significant increase in the use of these tools after the launch of ChatGPT 3.5 (9.4% in 2022 and 12.6% in 2023 [p=0.004]). The number of articles with suspected AI rates of greater than 10 and 20% were significantly higher in 2023: >10%: 71 articles (34.8%) versus 89 articles (47.8%) (p=0.008) and >20%: 21 articles (10.3%) versus 40 articles (21.5%) (p=0.002). A risk factor analysis for LLLM use, demonstrated that authors of Asian geographic origin, and the submission year 2023 were associated with a higher rate of suspected AI use. An AI rate >20% was associated to Asian geographical origin with an odds ratio of 1.79 (95% CI: 1.03-3.11) (p=0.029), while the year of submission being 2023 had an odds ratio of 1.7 (95% CI: 1.1-2.5) (p=0.02). CONCLUSION: This study highlights a significant increase in the use of LLM in the writing of articles submitted to the OTSR journal after the launch of ChatGPT 3.5. The increasing use of these models raises questions about originality and plagiarism in scientific research. AI offers creative opportunities but also raises ethical and methodological challenges. LEVEL OF EVIDENCE: III; case control study.

Narrow Band Imaging versus White Light for the Detection of Sessile Serrated Colorectal Lesions: A Randomized Clinical Trial.

Background: Colorectal cancer (CRC) is a leading cause of cancer. The detection of pre-malignant lesions by colonoscopy is associated with reduced CRC incidence and mortality. Narrow band imaging has shown promising but conflicting results for the detection of serrated lesions. Methods: We performed a randomized clinical trial to compare the mean detection of serrated lesions and hyperplastic polyps ≥10 mm with NBI or high-definition white light (HD-WL) withdrawal. We also compared all sessile serrated lesions (SSLs), adenoma, and polyp prevalence and rates. Results: Overall, 782 patients were randomized (WL group 392 patients; NBI group 390 patients). The average number of serrated lesions and hyperplastic polyps ≥10 mm detected per colonoscopy (primary endpoint) was similar between the HD-WL and NBI group (0.118 vs. 0.156, p = 0.44). Likewise, the adenoma detection rate (55.2% vs. 53.2%, p = 0.58) and SSL detection rate (6.8% vs. 7.5%, p = 0.502) were not different between the two study groups. Withdrawal time was higher in the NBI group (10.88 vs. 9.47 min, p = 0.004), with a statistically nonsignificant higher total procedure time (20.97 vs. 19.30 min, p = 0.052). Conclusions: The routine utilization of narrow band imaging does not improve the detection of serrated class lesions or any pre-malignant lesion and increases the withdrawal time.

Introdução: O cancro do cólon e reto é a neoplasia mais frequente considerando os dois géneros. . A deteção de lesões pré-malignas por colonoscopia está associada a uma redução da incidência e da mortalidade. Estudos sobre a utilização da luz de banda estreita (NBI) na deteção de lesões serreadas tiveram resultados promissores, mas heterogéneos. Métodos: Realizámos um ensaio clínico randomizado para comparar o número médio de lesões serreadas e lesões hiperplásicas ≥10 mm com NBI ou luz branca de alta-definição (HD-WL). Como resultados secundários comparámos a prevalência e as taxas de deteção de lesões serreadas sésseis, adenomas e todas as lesões. Resultados: Foram randomizados 782 doentes (392 no grupo HD-WL e 390 no grupo NBI). O número médio de lesões serreadas e hiperplásicas ≥10 mm não apresentou diferença estatisticamente significativa entre dois grupos (0.118 vs. 0.156, p = 0.44). A taxa de deteção de adenomas (55.2% vs. 53.2%, p = 0.58) e a taxa de deteção de lesões serreadas sésseis (6.8% vs. 7.5%, p = 0.502) também não foram diferentes. O tempo de retirada foi maior no grupo NBI (10.88 vs. 9.47 min, p = 0.004) e o tempo total de procedimento teve um ligeiro aumento não atingindo significância estatística (20.97 vs. 19.30 min, p = 0.052). Conclusão: A utilização da luz NBI por rotina não aumenta a deteção de lesões serreadas nem de qualquer lesão pré-maligna e aumenta o tempo de retirada na colonoscopia.

Identifying Consistent Metrics from the Force-Time Curve of the Countermovement Jump in Combat Fighters and Physically Active Men.

We investigated the consistency of metrics obtained from the unweighting, braking, propulsive, and landing phases of the countermovement (CMJ) force-time curve in combat fighters and physically active men. Combat fighters (n=21) and physically actives (n=21) were tested for three days (2-7 days apart). Participants performed four maximal CMJ separated by 1-min for between-day comparisons. From force-time recording, the consistency of 16 CMJ metrics (peak and mean ground reaction forces (GRF), net impulse, and duration from each phase) was investigated using the intraclass correlation coefficient (ICC) and typical error (CVTE). We considered as "consistent" those metrics showing no systematic differences, ICC ≥ 0.75, and CVTE ≤ 10%. We further compared the CVTE between groups and pairs of trials (days). Participants demonstrated more consistency in the braking and propulsive phases, while the unweighting phase did not show any consistent metric. There was no evidence of a learning effect (systematic changes), but analysis appointed more consistency on days 2-3 than on days 1-2 (18 metrics presented lower CVTE while 11 presented higher). We identified braking and propulsive GRF (peak and mean) and propulsive impulse as consistent metrics for combat fighters, while only propulsive impulse for physically actives. The between-group analyses showed that 24 comparisons favored the combat fighters against only five favoring the physically actives. In conclusion, force-time metrics related to jumping strategy, like phase duration, are less consistent than those related to driven forces and jump output, probably because participants changed their jump strategy during testing days.

PREDICTIVE FACTORS OF MORBIDITY ASSOCIATED WITH ESOPHAGEAL VARICEAL BLEEDING IN CHILDREN WITH PORTAL HYPERTENSION.

•Most data on the natural history of portal hypertension come from studies in adults. •The morbidity rate of upper gastrointestinal bleeding in children with portal hypertension tend to be underestimated. •This study showed the relevance of morbidity rates after variceal hemorrhage in pediatric patients, especially those with cirrhosis. •Patients with hemodynamic instability requiring blood transfusion or expansion on admission are at increased risk of complications secondary to upper gastrointestinal bleeding and should be closely monitored. Background - Most data on the natural history of portal hypertension come from studies in adults. The morbidity rate of upper gastrointestinal bleeding (UGIB) in children with portal hypertension has not been systematically characterized. Objective - To describe the morbidity and mortality of UGIB in pediatric patients with portal hypertension and identify predictive factors for the occurrence of its main complications. Methods - This retrospective study included pediatric patients with cirrhotic portal hypertension or with extrahepatic portal vein obstruction (EHPVO). Mortality and UGIB complications within a period of up to 6 weeks of the bleeding were investigated. To determine the predictive factors of morbidity, a multivariate analysis was performed using logistic regression; all results were considered significant at P<0.05. Results - A total of 86 patients (51.2% with EHPVO and 48.8% with cirrhosis) had 174 bleeding events. Ascites was the most common complication (43.1% of all cases), being more prevalent in patients with cirrhosis (P<0.001). Cirrhosis was a predictor of the occurrence of any morbidity (OR 20.3). The need for blood transfusion was predictor of at least one complication (OR 5.8), ascites (OR 7.2) and infections (OR 3.8) in the general group and at least one complication (OR 11.3) and ascites (OR 5.8) in cirrhotic patients. The need for expansion was a predictor of any morbidity (OR 4.6) and infections (OR 3.9) in the general group, in addition to being predictor of infection in cirrhotic patients (OR 5.4). There were no deaths from UGIB in the six weeks post-bleeding. Conclusion - The study showed the relevance of morbidity after UGIB in pediatric patients with portal hypertension, especially in those with cirrhosis. The patients with hemodynamic instability requiring blood transfusion or expansion on admission are at increased risk of complications related to upper gastrointestinal bleeding and should be closely monitored.

Time series causal relationships discovery through feature importance and ensemble models.

Inferring causal relationships from observational data is a key challenge in understanding the interpretability of Machine Learning models. Given the ever-increasing amount of observational data available in many areas, Machine Learning algorithms used for forecasting have become more complex, leading to a less understandable path of how a decision is made by the model. To address this issue, we propose leveraging ensemble models, e.g., Random Forest, to assess which input features the trained model prioritizes when making a forecast and, in this way, establish causal relationships between the variables. The advantage of these algorithms lies in their ability to provide feature importance, which allows us to build the causal network. We present our methodology to estimate causality in time series from oil field production. As it is difficult to extract causal relations from a real field, we also included a synthetic oil production dataset and a weather dataset, which is also synthetic, to provide the ground truth. We aim to perform causal discovery, i.e., establish the existing connections between the variables in each dataset. Through an iterative process of improving the forecasting of a target's value, we evaluate whether the forecasting improves by adding information from a new potential driver; if so, we state that the driver causally affects the target. On the oil field-related datasets, our causal analysis results agree with the interwell connections already confirmed by tracer information; whenever the tracer data are available, we used it as our ground truth. This consistency between both estimated and confirmed connections provides us the confidence about the effectiveness of our proposed methodology. To our knowledge, this is the first time causal analysis using solely production data is employed to discover interwell connections in an oil field dataset.

Mechanical demands of bite in plane head shapes of ant (Hymenoptera: Formicidae) workers.

Food processing can exert significant evolutionary pressures on the morphological evolution of animal appendages. The ant genus Pheidole displays a remarkable degree of morphological differentiation and task specialization among its workers. Notably, there is considerable variation in head shape within worker subcastes of Pheidole, which could affect the stress patterns generated by bite-related muscle contraction. In this study, we use finite element analysis (FEA) to investigate the effect of the variation in head plane shape in stress patterns, while exploring the morphospace of Pheidole worker head shapes. We hypothesize that the plane head shapes of majors are optimized for dealing with stronger bites. Furthermore, we expect that plane head shapes at the edges of each morphospace would exhibit mechanical limitations that prevent further expansion of the occupied morphospace. We vectorized five head shapes for each Pheidole worker type located at the center and edges of the corresponding morphospaces. We conducted linear static FEA to analyze the stresses generated by mandibular closing muscle contraction. Our findings indicate that plane head shapes of majors exhibit signs of optimization to deal with stronger bites. Stresses are distinctly directed along the lateral margins of the head, following the direction of muscle contraction, whereas the stresses on the plane head shapes of minors tend to concentrate around the mandibular articulations. However, the comparatively higher stress levels observed on majors' plane head shapes suggest a demand for cuticular reinforcement, like increased cuticle thickness or sculpturing pattern. Our results align with the expectations regarding the main colony tasks performed by each worker subcaste, and we find evidence of biomechanical limitations on extreme plane head shapes for majors and minors.

An Efficient Strategy for Electroreduction Reactor Outlet Fractioning into Valuable Products.

In this work, two industrial dual-step pressure swing adsorption (PSA) processes were designed and simulated to obtain high-purity methane, CO2, and syngas from a gas effluent of a CO2 electroreduction reactor using different design configurations. Among the set of zeolites that was investigated using Monte Carlo and molecular dynamics simulations, NaX and MFI were the ones selected. The dual-PSA process for case study 1 is only capable of achieving a 90.5% methane purity with a 95.2% recovery. As for case study 2, methane is obtained with a 97.5% purity and 95.3% recovery. Both case studies can produce CO2 with high purity and recovery (>97 and 95%, respectively) and syngas with a H2/CO ratio above 4. Although case study 2 allows methane to be used as domestic gas, a much higher value for its energy consumption is observed compared to case study 1 (64.9 vs 29.8 W h molCH4-1).